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Sample records for ccr connections news

  1. Repositioning news and public connection in everyday life

    DEFF Research Database (Denmark)

    Swart, Joëlle; Peters, Chris; Broersma, Marcel

    2017-01-01

    of public connection into four dimensions that emphasize people’s lived experiences: inclusiveness, engagement, relevance, and constructiveness. Situating these in an everyday life framework, this article advances a user-based perspective that considers the role of news for people in digital societies......News has traditionally served as a common ground, enabling people to connect to others and engage with the public issues they encounter in everyday life. This article revisits these theoretical debates about mediated public connection within the context of a digitalized news media landscape. While...

  2. News Media Literacy and Political Engagement: What's the Connection?

    Science.gov (United States)

    Ashley, Seth; Maksl, Adam; Craft, Stephanie

    2017-01-01

    Scholars and educators have long hoped that media education is positively related to pro-social goals such as political and civic engagement. With a focus on measuring news media literacy with emphasis on media knowledge, need for cognition and media locus of control, this study surveyed 537 college students and found positive relationships…

  3. News

    African Journals Online (AJOL)

    No news have been published. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL · News. OTHER RESOURCES... for Researchers · for Journals · for Authors · for Policy Makers · about ...

  4. Connected Paper, EKKO and Analytic Futures: News and Paper Data

    OpenAIRE

    Mills, John; Egglestone, Paul; Lochrie, Mark; Dickinson, Andrew Scott

    2015-01-01

    Advances in conductive inks and increasingly accessible and flexible platforms, such as Arduino and Raspberry Pi, are allowing researchers to transform a range of surfaces, including paper and additive layer objects, into capacitive surfaces. When imbued with Internet connectivity, and placed within the ‘Internet of things’, opportunities to create interactive surfaces that respond to touch and offer audio playback or other data transfer via additional connected peripherals emerge. This poste...

  5. News

    Science.gov (United States)

    2003-09-01

    Belfast: On the next level above Galileo Wales: 2nd All Wales Physics Teachers Meeting England: Good afternoon Natural Philosphers... Communication: Posters win prizes Careers: Physics On Course 2004 Visits: Refreshing Physics Sport: Cheating at baseball Physics on Stage: Polish performance Space: Forces that affect GPS satellites New Zealand: It’s not All Black News these days New Initiatives: NOISE Physics on Stage 3: Lively stars heading for ESA

  6. The Not5 subunit of the ccr4-not complex connects transcription and translation.

    Directory of Open Access Journals (Sweden)

    Zoltan Villanyi

    2014-10-01

    Full Text Available Recent studies have suggested that a sub-complex of RNA polymerase II composed of Rpb4 and Rpb7 couples the nuclear and cytoplasmic stages of gene expression by associating with newly made mRNAs in the nucleus, and contributing to their translation and degradation in the cytoplasm. Here we show by yeast two hybrid and co-immunoprecipitation experiments, followed by ribosome fractionation and fluorescent microscopy, that a subunit of the Ccr4-Not complex, Not5, is essential in the nucleus for the cytoplasmic functions of Rpb4. Not5 interacts with Rpb4; it is required for the presence of Rpb4 in polysomes, for interaction of Rpb4 with the translation initiation factor eIF3 and for association of Rpb4 with mRNAs. We find that Rpb7 presence in the cytoplasm and polysomes is much less significant than that of Rpb4, and that it does not depend upon Not5. Hence Not5-dependence unlinks the cytoplasmic functions of Rpb4 and Rpb7. We additionally determine with RNA immunoprecipitation and native gel analysis that Not5 is needed in the cytoplasm for the co-translational assembly of RNA polymerase II. This stems from the importance of Not5 for the association of the R2TP Hsp90 co-chaperone with polysomes translating RPB1 mRNA to protect newly synthesized Rpb1 from aggregation. Hence taken together our results show that Not5 interconnects translation and transcription.

  7. News

    OpenAIRE

    News, Transfer

    2017-01-01

      NOTICIAS / NEWS (“transfer”, 2018)  1) LIBROS – CAPÍTULOS DE LIBRO  / BOOKS – BOOK CHAPTERS 1. Bandia, Paul F. (ed.). (2017). Orality and Translation.  London: Routledge.   2. Trends in Translation and Interpretin,  Institute of Translation & Interpreting 3. Schippel, Larisa & Cornelia Zwischenberger. (eds). (2017). Going East: Discovering New and Alternative Traditions in Translation Studies. Berlin: Frank & Timme. 4.  Godayol, Pilar. (2017). Tres escritoras censuradas: Simone de Beauvoir,...

  8. news

    Directory of Open Access Journals (Sweden)

    Marina Tkacheva

    2012-02-01

    Full Text Available XXIV World Congress of Architecture – UIA Tokyo 2011UIA NewsTuva Architects' SuccessRecollection of "Zodchestvo 2011""Children Are not People of Tomorrow, but Are People of Today with a Different Scale of Feelings and Experience"The 30th Anniversary of the Union of Architects of RussiaXX International Review Competition for the Best Graduation Architecturaland Design Projects (YerevanParticipation of the Design Department of National Research Irkutsk State Technical UniversityParticipation of Institute of Architecture and Construction of National Research Irkutsk State Technical UniversitySeven Years and Further on!Breathe Together!VI Special Meeting of the National Association of DesignersWhat is Good for a German… or a Russian-Style SRO2012. "Katastrofa" Festival. AdvertisementSummer Workshop of Les Ateliers of Urban Planning and Development (Cergy-Pontoise, France

  9. CCR1

    African Journals Online (AJOL)

    Chemokine Receptor 1 (CCR1) Derived from Viral ... the potential role and mechanism of peptide C18P derived from viral macrophage inflammatory protein ..... 4. Kauts ML, Pihelgas S, Orro K, Neuman T, Piirsoo A. CCL5/CCR1 axis regulates multipotency of human adipose tissue derived stromal cells. Stem Cell Res. 2013 ...

  10. Bots as a news service and its emotional connectivity with the audience. The case of Politibot

    Directory of Open Access Journals (Sweden)

    Hada M. Sánchez Gonzales

    2017-11-01

    Full Text Available It is evident that users are permanently and ubiquitously connected to the network through their mobile devices. As a consequence, they can access to an extraordinary quantity of information. Journalism has tools that, by using artificial intelligence and instant messaging systems, send filtered and personalized information to users. These systems are the so called chat bots or conversational applications. While the big media companies are developing their own applications via Messenger or Telegram, there also exist other companies that provide this type of services. That is the case of Politibot, a service that was launched during the June 2016 election campaign in Spain and which had gained 8,400 subscribers a month later. This paper analyzes this case in order to determine the way audiences perceive and consider bots news. To do so, we apply, among other techniques, observation of Politibots publications via Telegram, survey of users and analysis of social media feedback. We aim to answer questions such as how users differentiate and value bots news, how conversation in these platforms is produced, and how to collect more reliable data from them. Results show that information quality (73.1% of answers and the emotional connection they establish with the tool (26, 8% are the main potential of these formulas, which are becoming in an opportunity for journalism.

  11. Clinical Case Registries (CCR)

    Data.gov (United States)

    Department of Veterans Affairs — The Clinical Case Registries (CCR) replaced the former Immunology Case Registry and the Hepatitis C Case Registry with local and national databases. The CCR:HIV and...

  12. Development of Tetravalent, Bispecific CCR5 Antibodies with Antiviral Activity against CCR5 Monoclonal Antibody-Resistant HIV-1 Strains▿

    Science.gov (United States)

    Schanzer, Jürgen; Jekle, Andreas; Nezu, Junichi; Lochner, Adriane; Croasdale, Rebecca; Dioszegi, Marianna; Zhang, Jun; Hoffmann, Eike; Dormeyer, Wilma; Stracke, Jan; Schäfer, Wolfgang; Ji, Changhua; Heilek, Gabrielle; Cammack, Nick; Brandt, Michael; Umana, Pablo; Brinkmann, Ulrich

    2011-01-01

    In this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats that we applied were derived from Morrison-type bispecific antibodies: whole IgGs to which we connected single-chain antibodies (scFvs) via (Gly4Ser)n sequences at either the C or N terminus of the light chain or heavy chain. By design optimization, including disulfide stabilization of scFvs or introduction of 30-amino-acid linkers, stable molecules could be obtained in amounts that were within the same range as or no less than 4-fold lower than those observed with monoclonal antibodies in transient expression assays. In contrast to monospecific CCR5 antibodies, bispecific antibody derivatives block two alternative docking sites of CCR5-tropic HIV strains on the CCR5 coreceptor. Consequently, these molecules showed 18- to 57-fold increased antiviral activities compared to the parent antibodies. Most importantly, one prototypic tetravalent CCR5 antibody had antiviral activity against virus strains resistant to the single parental antibodies. In summary, physical linkage of two CCR5 antibodies targeting different epitopes on the HIV coreceptor CCR5 resulted in tetravalent, bispecific antibodies with enhanced antiviral potency against wild-type and CCR5 antibody-resistant HIV-1 strains. PMID:21300827

  13. CCR1 and CCR5 expressions on peripheral blood mononuclear ...

    African Journals Online (AJOL)

    Isolated PBMCs from 25 patients with HCC, 10 LC patients and 9 adult healthy controls were stained with monoclonal antibodies against CD4, CD8, CCR1 and CCR5, then detected by using a flow cytometry technique. Patients were diagnosed by abdominal ultrasound (US) and computed tomography (CT) scan findings, ...

  14. Implication of Ccr4-Not complex function in mRNA quality control in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Assenholt, Jannie; Mouaikel, John; Saguez, Cyril

    2011-01-01

    RNPs are exported to the cytoplasm. The Ccr4-Not complex, which constitutes the major S. cerevisiae cytoplasmic deadenylase, has recently been implied in nuclear exosome–related processes. Consistent with a possible nuclear function of the complex, the deletion or mutation of Ccr4-Not factors also elicits...... transcription phenotypes. Here we use genetic depletion of the Mft1p protein of the THO transcription/mRNP packaging complex as a model system to link the Ccr4-Not complex to nuclear mRNP QC. We reveal strong genetic interactions between alleles of the Ccr4-Not complex with both the exosomal RRP6 and MFT1 genes....... Moreover, Rrp6p-dependent in vivo QC phenotypes of Δmft1 cells can be rescued by codeletion of several Ccr4-Not components. We discuss how the Ccr4-Not complex may connect with the mRNP QC pathway...

  15. Networks in the news media

    DEFF Research Database (Denmark)

    Bro, Peter

    When news reporters connect people in a single news story or in a series of coherent news stories they essentially construct networks in the news media. Networks through which social actors are aligned symbolically in written, visible or audible form. These socio-symbolic networks not only copy...... more formal types of social networks, but also complement or even substitute social networking elsewhere, and as such this particular type of social network offers people both inside and outside the news room new potentials - and problems. This article describe the basic vision of networks in the news...... media and discuss the importance of this analytical framework when it comes to understanding prevailing forms and norms in contemporary journalism....

  16. News for assimilation or integration

    Science.gov (United States)

    Alencar, Amanda; Deuze, Mark

    2017-04-01

    This study investigates the functions of news media in shaping acculturation experiences of new economic and refugee immigrants in the Netherlands and Spain. Focus group data revealed that consumption of host country news media was mainly connected to immigrants' deliberate strategies to assimilate the culture, politics and language of the host society, while exposure to transnational news was viewed in terms of strategies of integration in both countries. We also observed that participants' educational background and language skills combined with their perceptions of the host country's news have an impact on the use they make of news for assimilating and/or integrating into the host society. Finally, important sociopolitical conditions of the context influenced the ways participants use the news media in their process of acculturation.

  17. Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

    OpenAIRE

    Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Diaz-Griffero, Felipe; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Sekaly, Rafick-Pierre; Ancuta, Petronela

    2009-01-01

    There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 a...

  18. Getting Connected

    Science.gov (United States)

    Larkin, Patrick

    2011-01-01

    That the world outside schools is changing faster than ever is old news. Unfortunately, that the world "inside" schools is changing at a glacial pace is even older news. As school leaders, principals have an important choice to make as they move into the second decade of the 21st century. School leaders have a moral obligation to connect and…

  19. PUSHED NEWS: When the news comes to the cellphone

    Directory of Open Access Journals (Sweden)

    Antonio Fidalgo

    2009-12-01

    Full Text Available Combining two findings of recent surveys on the Internet whichstate that 1 “the Internet will soon surpass all other media as a main source for national and international news” and 2 “the mobile device will be the primary connection tool to the Internet in 2020” leads us to the conclusion that smartphones will soon be the primary source for news access. But if so, how will news come to the Internetconnected cellphones? In accordance with the distinction, already drawn in 1997, between push and pull technologies as two different forms of how content is delivered to the end users, cellphones are characterized as push devices (passive reception, in opposition to computers, classified as pull devices (active reception. The news items that fit cellphones are pushed news. And they will be pushed as SMS, e-mails, tweets and through news aggregators.

  20. Pushed news: when the news comes to the cellphone

    Directory of Open Access Journals (Sweden)

    Antonio Fidalgo

    2009-12-01

    Full Text Available Combining two findings of recent surveys on the Internet which state that 1 “the Internet will soon surpass all other media as a main source for national and international news” and 2 “the mobile device will be the primary connection tool to the Internet in 2020” leads us to the conclusion that smartphones will soon be the primary source for news access. But if so, how will news come to the Internetconnected cellphones? In accordance with the distinction, already drawn in 1997, between push and pull technologies as two different forms of how content is delivered to the end users, cellphones are characterized as push devices (passive reception, in opposition to computers, classified as pull devices (active reception. The news items that fit cellphones are pushed news. And they will be pushed as SMS, e-mails, tweets and through news aggregators.

  1. News | FNLCR

    Science.gov (United States)

    Consortium aims to accelerate drug discovery process(Physics Today) Why big pharma and biotech are betting big on AI(NBC News) Scientists launch SF-based effort to dramatically cut cancer drug discovery time(SF Chronicle

  2. Regulation of CCR7-dependent cell migration through?CCR7 homodimer formation

    OpenAIRE

    Kobayashi, Daichi; Endo, Masataka; Ochi, Hirotaka; Hojo, Hironobu; Miyasaka, Masayuki; Hayasaka, Haruko

    2017-01-01

    The chemokine receptor CCR7 contributes to various physiological and pathological processes including T cell maturation, T cell migration from the blood into secondary lymphoid tissues, and tumor cell metastasis to lymph nodes. Although a previous study suggested that the efficacy of CCR7 ligand-dependent T cell migration correlates with CCR7 homo- and heterodimer formation, the exact extent of contribution of the CCR7 dimerization remains unclear. Here, by inducing or disrupting CCR7 dimers,...

  3. No news is good news?

    CERN Document Server

    Peter Schmid

    I'm retired and living back home in Austria. But I am still excited about ATLAS and I try to follow the progress of the project as closely as I can. The ATLAS e-news are an excellent source of information. Appearing now every month they provide a broad, solid view of what is going on. But I'm greedy; I'd love to be "on-line". When the first End-Cap Toroid moved from hall 180 to the pit I was frustrated. I knew that it was happening but I could only get first pictures and reports a few days later. In the meantime the ECT was lowered into the cavern; no information on this available nowhere up to the this issue of the e-news. Here is my dream: an "ATLAS news ticker", i.e. a web page with the news appearing on the day they happen; just one line of information, possibly with a reference to a picture, a person or a report. My idea isn't new. On the ATLAS web-site for the public we have a window "latest news". But I was disappointed when, until a week ago, the latest news dated from December 2006 !!! Can't we do...

  4. The News Media Industry

    National Research Council Canada - National Science Library

    Bartlett, Charlie

    2003-01-01

    ...: attitudes toward the news, news consumption, interest in international news, consolidation, government deregulation, coverage of national security issues, "infotainment," and the "digital revolution...

  5. NEWS: Institute news

    Science.gov (United States)

    2000-07-01

    Department of Physics and Astronomy at the University of Leeds. Physics at Work Exhibition: 12-14 September, University of Cambridge The year 2000 Exhibition will be the 16th organized by Brenda Jennison. The exhibition will be held at the Cavendish Laboratory and further details can be obtained from Brenda at the University (tel: 01223 332888, fax: 01223 332894 or e-mail: bmj10@cam.ac.uk). News on GNVQ science The Institute of Physics and the Royal Society of Chemistry are currently financing the compilation of a directory of resources to assist teachers in identifying and selecting suitable materials for teaching the new GNVQ science specifications. Work on the first part of the directory will soon be completed and it is hoped to publish the material in both print and electronic forms before the end of the summer term. This first part covers resources - all evaluated by practising GNVQ teachers - supporting the teaching of the compulsory units for Advanced GNVQ Science. A small team comprising a physics teacher, a chemistry teacher and a biology teacher, all involved with GNVQ programmes and led by Dr Ken Gadd, has carried out the work. They have established a network of teachers around the country to help with the evaluation of curriculum materials. The next part of the project will be to examine the feasibility of providing a similar listing for the optional units at this level. Future development, depending on the availability of funds, will extend the project to Intermediate level programmes in science, including the Part One, once its structure has been agreed at QCA. Further information about the Directory and the next phase of development will be available in the autumn. Activities Physics on Stage The future of science, technology and the ensuing wealth creation potential for Britain will depend on the quality of science education in schools today. Yet the numbers studying physics, which underpins science and engineering, are falling. This problem is currently

  6. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P

    2001-01-01

    and macrophage inflammatory protein-1alpha/CCL3. We analyzed expression of CCR1 and CCR5, the monocyte receptors for these chemokines, on circulating and cerebrospinal fluid CD14+ cells, and in MS brain lesions. Approximately 70% of cerebrospinal fluid monocytes were CCR1+/CCR5+, regardless of the presence...... of CNS pathology, compared to less than 20% of circulating monocytes. In active MS lesions CCR1+/CCR5+ monocytes were found in perivascular cell cuffs and at the demyelinating edges of evolving lesions. Mononuclear phagocytes in early demyelinating stages comprised CCR1+/CCR5+ hematogenous monocytes...... and CCR1-/CCR5- resident microglial cells. In later stages, phagocytic macrophages were uniformly CCR1-/CCR5+. Cultured in vitro, adherent monocytes/macrophages up-regulated CCR5 and down-regulated CCR1 expression, compared to freshly-isolated monocytes. Taken together, these findings suggest...

  7. News & Announcements

    Science.gov (United States)

    2001-08-01

    , College Park, October 14-17, 2001. NEW: Update, is a partnership involving industry, government, and education. It will have a program of Experiments and Demonstrations, Mini Workshops, and Plenary Sessions. For registration information, contact Jim Jacobs, NEW: Update 2001, School of Science and Technology, Norfolk State University, Norfolk, VA 23504-8060; phone: 757/823-8109/9072; fax: 757/823-8215; dplaclaire@nsu.edu. The latest information about the workshop will be at http://MST-Online.nsu.edu/new. Chemistry Is in the News Conference Chemistry Is in the News-Teaching Organic Chemistry in the Context of Real World Issues, will be held at the University of Missouri-Columbia September 21-23, 2001. Funding from the Dreyfus Foundation will support 18 participants and will offer some partial travel grants. The conference will instruct faculty about the philosophy, pedagogy, implementation, and assessment of the project, doing so in small collaborative groups. It will focus on facilitating news-media-based authentic learning activities aimed at connecting real-world social, economic, and political issues to the teaching of organic chemistry and the development of student-assisted collaborative learning groups. The conference organizers are Rainer Glaser and James Groccia. Those interested should contact Rainer Glaser, University of Missouri, Department of Chemistry, Columbia, MO 65211; phone: 573/882-0331; fax: 573/882-2754; GlaserR@missouri.edu. ChemNet-Chemistry Lecture on the Internet A multimedia chemistry lecture, developed by R. Demuth, S. Nick, K. Rabe, L. Lensment, S. Schanze, J. Andresen, and W. Bensch of the University of Kiel, Germany, is being provided without charge over the Internet. The lecture is directed at students of chemistry, agricultural science, medicine, biology, and engineering and other interested persons. The lecture is in German but an English version is planned. With the aid of ChemNet the group plans to attain some information on the use and

  8. Molekulare Klonierung, stabile Transfektion und funktionelle Expression der murinen Chemokinrezeptoren Ccr2 und Ccr5

    OpenAIRE

    Simonis, Christopher

    2009-01-01

    The two chemokine receptors CCR2 and CCR5 play important roles in the recruitment and activation of monocytes/macrophages and T-lymphocytes at sites of infection and inflammation. To further examine their function, I cloned the two murine chemokine receptors Ccr2 and Ccr5 from genomic mouse DNA by a PCR-based cloning strategy and functionally expressed them in stably transfected CHO-cells. These cells were used to generate the first monoclonal antibodies against Ccr2 and Ccr5.

  9. Fake News

    Science.gov (United States)

    Frederiksen, Linda

    2017-01-01

    In a politically and digitally polarized environment, identifying and evaluating fake news is more difficult than ever before. Librarians who have been teaching information and media literacy skills for decades understand the role we can and must play in this environment.

  10. CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

    Science.gov (United States)

    Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong; Kim, Ju Han

    2014-01-01

    Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

  11. The frequency of CCR5 promoter polymorphisms and CCR5 32 mutation in Iranian populations

    Directory of Open Access Journals (Sweden)

    Mohammad Zare-Bidaki

    2015-04-01

    Full Text Available Evidence showed that chemokines serve as pro-migratory factors for immune cells. CCL3, CCL4 and CCL5, as the main CC  chemokines subfamily members, activate immune cells through binding to CC chemokine receptor 5 or CCR5. Macrophages, NK cells and T lymphocytes express CCR5 and thus, affected CCR5 expression or functions could be associated with altered immune responses. Deletion of 32 base pairs (D 32 in the exon 1 of the CCR5 gene, which is known as CCR5 D 32 mutation causes down regulation and malfunction of the molecule. Furthermore, it has been evidenced that three polymorphisms in the promoter region of CCR5 modulate its expression. Altered CCR5 expression in microbial infection and immune related diseases have been reported by several researchers but the role of CCR5 promoter polymorphisms and CCR5 D 32 mutation in Iranian patients suffering from these diseases are controversial. Due to the fact that Iranian people have different genetic backgrounds compared to other ethnics, hence, CCR5 promoter polymorphisms and CCR5 D 32 mutation association with the diseases may be different in Iranian patients. Therefore, this review addresses the most recent information regarding the prevalence as well as association of the mutation and polymorphisms in Iranian patients with microbial infection and immune related diseases as along with normal population.

  12. CCR2, CCR5, and CXCL12 variation and HIV/AIDS in Papua New Guinea.

    Science.gov (United States)

    Mehlotra, Rajeev K; Hall, Noemi B; Bruse, Shannon E; John, Bangan; Zikursh, Melinda J Blood; Stein, Catherine M; Siba, Peter M; Zimmerman, Peter A

    2015-12-01

    Polymorphisms in chemokine receptors, serving as HIV co-receptors, and their ligands are among the well-known host genetic factors associated with susceptibility to HIV infection and/or disease progression. Papua New Guinea (PNG) has one of the highest adult HIV prevalences in the Asia-Pacific region. However, information regarding the distribution of polymorphisms in chemokine receptor (CCR5, CCR2) and chemokine (CXCL12) genes in PNG is very limited. In this study, we genotyped a total of nine CCR2-CCR5 polymorphisms, including CCR2 190G >A, CCR5 -2459G >A and Δ32, and CXCL12 801G >A in PNG (n=258), North America (n=184), and five countries in West Africa (n=178). Using this data, we determined previously characterized CCR5 haplotypes. In addition, based on the previously reported associations of CCR2 190, CCR5 -2459, CCR5 open reading frame, and CXCL12 801 genotypes with HIV acquisition and/or disease progression, we calculated composite full risk scores, considering both protective as well as susceptibility effects of the CXCL12 801 AA genotype. We observed a very high frequency of the CCR5 -2459A allele (0.98) in the PNG population, which together with the absence of Δ32 resulted in a very high frequency of the HHE haplotype (0.92). These frequencies were significantly higher than in any other population (all P-valuesnew insights regarding CCR5 variation in the PNG population, and suggest that the collective variation in CCR2, CCR5, and CXCL12 may increase the risk of HIV/AIDS in a large majority of Papua New Guineans. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. FAKE NEWS

    DEFF Research Database (Denmark)

    Hendricks, Vincent Fella; Vestergaard, Mads

    Politik og medier oversvømmes af fordrejninger, fortielser, forglemmelser og forvanskninger af sandheden. Vi invaderes af populistiske fortællinger, “alternative kendsgerninger” og “fake news”. Det er nu et faktum, at misinformation er noget man aktivt må forholde sig til som politiker, som...... for virkelige udfordringer, vi står over for. FAKE NEWS giver et første sammenhængende billede af hvordan opmærksomhedsøkonomien kan ende i det postfaktuelle demokrati: Eventyrlige fortællinger erstatter kendsgerninger som grundlag for politisk meningsdannelse, debat og lovgivning. Et monster, som de færreste...

  14. news-please

    OpenAIRE

    Hamborg, Felix; Meuschke, Norman; Breitinger, Corinna; Gipp, Bela

    2017-01-01

    The amount of news published and read online has increased tremendously in recent years, making news data an interesting resource for many research disciplines, such as the social sciences and linguistics. However, large scale collection of news data is cumbersome due to a lack of generic tools for crawling and extracting such data. We present news-please, a generic, multilanguage, open-source crawler and extractor for news that works out-of-thebox for a large variety of news websites. ...

  15. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...

  16. Influence of the CCR2-V64I Polymorphism on Human Immunodeficiency Virus Type 1 Coreceptor Activity and on Chemokine Receptor Function of CCR2b, CCR3, CCR5, and CXCR4

    OpenAIRE

    Lee, Benhur; Doranz, Benjamin J.; Rana, Shalini; Yi, Yanji; Mellado, Mario; Frade, Jose M. R.; Martinez-A., Carlos; O’Brien, Stephen J.; Dean, Michael; Collman, Ronald G.; Doms, Robert W.

    1998-01-01

    The chemokine receptors CCR5 and CXCR4 are used by human immunodeficiency virus type 1 (HIV-1) in conjunction with CD4 to infect cells. In addition, some virus strains can use alternative chemokine receptors, including CCR2b and CCR3, for infection. A polymorphism in CCR2 (CCR2-V64I) is associated with a 2- to 4-year delay in the progression to AIDS. To investigate the mechanism of this protective effect, we studied the expression of CCR2b and CCR2b-V64I, their chemokine and HIV-1 coreceptor ...

  17. Constrained use of CCR5 on CD4+ lymphocytes by R5X4 HIV-1: Efficiency of Env-CCR5 interactions and low CCR5 expression determine a range of restricted CCR5-mediated entry

    OpenAIRE

    Loftin, Lamorris M.; Kienzle, Martha F.; Yi, Yanjie; Lee, Benhur; Lee, Fang-Hua; Gray, Lachlan; Gorry, Paul R.; Collman, Ronald G.

    2010-01-01

    R5X4 HIV-1 have impaired utilization of CCR5 on primary CD4+ lymphocytes but the mechanisms responsible are not well defined. Using a panel of diverse R5X4 Envs we identified a spectrum of CCR5 use on CD4+ lymphocytes. Greater lymphocyte CCR5 use correlated with relative resistance to CCR5 mAbs and small molecule antagonists. Increasing CCR5 expression on lymphocytes increased the proportion of entry mediated by CCR5 for all R5X4 isolates except 89.6. In cell lines with regulated CCR5 express...

  18. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P

    2007-01-01

    OBJECTIVE: To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta). METHODS: The CCR5 Delta32 allele and a CCR5 promoter polymorphism associated with cell surface expression of CCR5 were...... analyzed in 109 patients with relapsing-remitting MS treated with IFN-beta who were followed clinically for 1 year. Cellular CCR5 expression was measured by flow cytometry. RESULTS: Patients with MS had a higher percentage of CCR5-positive monocytes than healthy controls. Increased monocyte expression...... of CCR5 correlated weakly with an increased short-term relapse risk but there was no relationship between CCR5 Delta32 allele and CCR5 promoter polymorphism genotypes and relapse risk. CONCLUSIONS: The results do not support a major role of CCR5 in the pathogenesis of relapses in MS patients treated...

  19. Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis

    OpenAIRE

    Lebre, M.C.; Vergunst, C.E.; Choi, I.Y.K.; Aarrass, S.; Oliveira, A.S.F.; Wyant, T.; Horuk, R.; Reedquist, K.A.; Tak, P.P.

    2011-01-01

    BACKGROUND: The aim of this study was to provide more insight into the question as to why blockade of CCR1, CCR2, and CCR5 may have failed in clinical trials in rheumatoid arthritis (RA) patients, using an in vitro monocyte migration system model. METHODOLOGY/PRINCIPAL FINDINGS: Monocytes from healthy donors (HD; n = 8) or from RA patients (for CCR2 and CCR5 antibody n = 8; for CCR1 blockade n = 13) were isolated from peripheral blood and pre-incubated with different concentrations of either ...

  20. Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)

    OpenAIRE

    Fagin, Ursula; Pitann, Silke; Gross, Wolfgang L; Lamprecht, Peter

    2012-01-01

    Introduction Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polari...

  1. CCR3, CCR5, CCR8 and CXCR3 expression in memory T helper cells from allergic rhinitis patients, asymptomatically sensitized and healthy individuals

    DEFF Research Database (Denmark)

    Holse, Mille; Assing, Kristian; Poulsen, Lars K.

    2006-01-01

    Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial.......Chemokine receptors have been suggested to be preferentially expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset and CCR5 and CXCR3 to the Th1 subset, however this remains controversial....

  2. Development of Tetravalent, Bispecific CCR5 Antibodies with Antiviral Activity against CCR5 Monoclonal Antibody-Resistant HIV-1 Strains▿

    OpenAIRE

    Schanzer, Jürgen; Jekle, Andreas; Nezu, Junichi; Lochner, Adriane; Croasdale, Rebecca; Dioszegi, Marianna; Zhang, Jun; Hoffmann, Eike; Dormeyer, Wilma; Stracke, Jan; Schäfer, Wolfgang; Ji, Changhua; Heilek, Gabrielle; Cammack, Nick; Brandt, Michael

    2011-01-01

    In this study, we describe novel tetravalent, bispecific antibody derivatives that bind two different epitopes on the HIV coreceptor CCR5. The basic protein formats that we applied were derived from Morrison-type bispecific antibodies: whole IgGs to which we connected single-chain antibodies (scFvs) via (Gly4Ser)n sequences at either the C or N terminus of the light chain or heavy chain. By design optimization, including disulfide stabilization of scFvs or introduction of 30-amino-acid linker...

  3. Measuring News Media Literacy

    Science.gov (United States)

    Maksl, Adam; Ashley, Seth; Craft, Stephanie

    2015-01-01

    News media literacy refers to the knowledge and motivations needed to identify and engage with journalism. This study measured levels of news media literacy among 500 teenagers using a new scale measure based on Potter's model of media literacy and adapted to news media specifically. The adapted model posits that news media literate individuals…

  4. The Cognitive Information Effect of Televised News

    Directory of Open Access Journals (Sweden)

    George Lăzăroiu

    2017-07-01

    Full Text Available The purpose of this review is to summarize the key findings which prove that the biased perceptions of viewers may provide an inaccurate image of the informational validity of televised news. The news may generate distorted recollections of what occurred in particular reported events if displayed routines influence viewers not to pay attention to the essential features of a narrative. Elaborating on Fiske and Hartley (2010, Zelizer (2010, and Gunter (2015, we indicate that the character of the news setting has altered and individuals’ news consumption routines have changed in adapting to media advancements. The news may be undergone at various psychological stages by news publics. Televised news may transmit information undeviatingly to publics that may (not be committed successfully to memory. Our paper shows that individuals’ skills to handle information that is displayed in a linguistic configuration are influenced by their abilities in the utilization of certain symbol systems that are employed to represent notions and meanings. Televised news may shape what individuals grasp, influence their perceptions, convictions, and views regarding prevailing events and matters, and transmit knowledge and interpretation. If news stories can be jotted down in a linguistic style that sidesteps making needless processing demands and captivate news users by facilitating them to make connections with former knowledge, they may be more worthy of note and more edifying. We conclude that news narratives present a cognitive demanding task to individuals, displaying novel information regarding evolving events in a multifarious format. Broadcast news exhibits intricate contents, displaying configurations that employ excessively the cognitive abilities for information processing of viewers.

  5. The Cognitive Information Effect of Televised News.

    Science.gov (United States)

    Lăzăroiu, George; Pera, Aurel; Ştefănescu-Mihăilă, Ramona O; Bratu, Sofia; Mircică, Nela

    2017-01-01

    The purpose of this review is to summarize the key findings which prove that the biased perceptions of viewers may provide an inaccurate image of the informational validity of televised news. The news may generate distorted recollections of what occurred in particular reported events if displayed routines influence viewers not to pay attention to the essential features of a narrative. Elaborating on Fiske and Hartley (2010), Zelizer (2010), and Gunter (2015), we indicate that the character of the news setting has altered and individuals' news consumption routines have changed in adapting to media advancements. The news may be undergone at various psychological stages by news publics. Televised news may transmit information undeviatingly to publics that may (not) be committed successfully to memory. Our paper shows that individuals' skills to handle information that is displayed in a linguistic configuration are influenced by their abilities in the utilization of certain symbol systems that are employed to represent notions and meanings. Televised news may shape what individuals grasp, influence their perceptions, convictions, and views regarding prevailing events and matters, and transmit knowledge and interpretation. If news stories can be jotted down in a linguistic style that sidesteps making needless processing demands and captivate news users by facilitating them to make connections with former knowledge, they may be more worthy of note and more edifying. We conclude that news narratives present a cognitive demanding task to individuals, displaying novel information regarding evolving events in a multifarious format. Broadcast news exhibits intricate contents, displaying configurations that employ excessively the cognitive abilities for information processing of viewers.

  6. CCR Interns | Center for Cancer Research

    Science.gov (United States)

    The Cancer Research Interns (CRI) Summer Program was inaugurated in 2004 to increase the diversity of trainee applicants to the Center for Cancer Research (CCR). We have placed 339 students from 2004 to 2017, in labs and branches across the CCR. The Division provides the training dollars, some Service & Supply funds, and travel support for those students who meet the financial eligibility criteria (View and/or print the 2018 flier).

  7. Novae news

    CERN Multimedia

    2012-01-01

    As announced in the previous Bulletin, Novae has opened a new snack bar on the Flagstaff car park, just a few metres from CERN's reception area (Building 33).   Just a few metres from the CERN Reception, the new Novae snack point welcomes visitors and CERNois. Opening hours Currently: Monday to Friday, 8 a.m. to 4 p.m. From September: Monday to Friday, 7:45 a.m. to 5 p.m.; Saturdays from 8 a.m. to 2 p.m. The snack bar selection includes breakfast, starting at 2.70 CHF, cold dishes from 5 CHF, and hot dishes from 6 CHF.   Novae has also installed a 24-hour-a-day food vending machine in the CERN hostel (Building 39) and in Building 13. You can buy pasta and cooked dishes for 6.50 CHF to 8 CHF. In addition, a groceries vending machine has been installed in the main building, just across from the news kiosk. Nearly 60 different items are available around the clock. Finally, Novae has introduced a new payment system in several buildings on the Meyrin site. It accepts credit ca...

  8. Physics News

    CERN Multimedia

    Gianotti, F.

    In spite of the fact that real data will only come in the year 2006, this is a very busy and interesting time for Physics-related activities. A very short overview of these activities is given in this issue of the ATLAS News Letter, while the various topics will be described in more detail in the next issues. The Physics and Combined Performance groups are working in four main areas: 1) Assess the ATLAS potential for physics, with emphasis on new channels and ideas. Recent examples are Extra-dimensions, invisible Higgs decays, heavy ion physics, the expected potential of a "Super-LHC" running at a luminosity of 10^35, etc.. 2) Improve the understanding of the detector performance and optimise the reconstruction algorithms. Examples of issues in the pipeline are: can we tag charm-jet ? What can we gain in the jet energy resolution by combining the calorimeter and tracker information to reconstruct the jet energy ? 3) Follow detector changes and detector-related issues and monitor the impact on the perform...

  9. Stimulation of oral fibroblast chemokine receptors identifies CCR3 and CCR4 as potential wound healing targets

    Science.gov (United States)

    Buskermolen, Jeroen K.; Roffel, Sanne

    2017-01-01

    The focus of this study was to determine which chemokine receptors are present on oral fibroblasts and whether these receptors influence proliferation, migration, and/or the release of wound healing mediators. This information may provide insight into the superior wound healing characteristics of the oral mucosa. The gingiva fibroblasts expressed 12 different chemokine receptors (CCR3, CCR4, CCR6, CCR9, CCR10, CXCR1, CXCR2, CXCR4, CXCR5, CXCR7, CX3CR1, and XCR1), as analyzed by flow cytometry. Fourteen corresponding chemokines (CCL5, CCL15, CCL20, CCL22, CCL25, CCL27, CCL28, CXCL1, CXCL8, CXCL11, CXCL12, CXCL13, CX3CL1, and XCL1) were used to study the activation of these receptors on gingiva fibroblasts. Twelve of these fourteen chemokines stimulated gingiva fibroblast migration (all except for CXCL8 and CXCL12). Five of the chemokines stimulated proliferation (CCL5/CCR3, CCL15/CCR3, CCL22/CCR4, CCL28/CCR3/CCR10, and XCL1/XCR1). Furthermore, CCL28/CCR3/CCR10 and CCL22/CCR4 stimulation increased IL‐6 secretion and CCL28/CCR3/CCR10 together with CCL27/CCR10 upregulated HGF secretion. Moreover, TIMP‐1 secretion was reduced by CCL15/CCR3. In conclusion, this in‐vitro study identifies chemokine receptor‐ligand pairs which may be used in future targeted wound healing strategies. In particular, we identified the chemokine receptors CCR3 and CCR4, and the mucosa specific chemokine CCL28, as having an predominant role in oral wound healing by increasing human gingiva fibroblast proliferation, migration, and the secretion of IL‐6 and HGF and reducing the secretion of TIMP‐1. PMID:28387445

  10. Extracellular Disulfide Bridges Serve Different Purposes in Two Homologous Chemokine Receptors, CCR1 and CCR5

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Thiele, Stefanie; Hansen, Laerke Smidt

    2013-01-01

    interact with residues in the main binding crevice, we show that the 7TM-conserved bridge is essential for all types of ligand-mediated activation, whereas the chemokine-conserved bridge is dispensable for small-molecule activation in CCR1. However, in striking contrast to previous studies in other...... chemokine receptors, high affinity CCL3 chemokine binding was maintained in the absence of either bridge. In CCR5, the closest homolog to CCR1, a completely different dependency was observed as neither chemokine activation nor binding was retained in the absence of either bridge. In contrast, both bridges...... where dispensable for small-molecule activation. This indicates that CCR5 activity is independent of extracellular regions, whereas in CCR1, preserved folding of ECL2 is necessary for activation. These results indicate that conserved structural features in a receptor subgroup, does not necessarily...

  11. CCL5, CCR1 and CCR5 in murine glioblastoma: immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5

    OpenAIRE

    Pham, Kien; Luo, Defang; Liu, Che; Harrison, Jeffrey K.

    2012-01-01

    Glioblastoma multiforme (GBM) is the most malignant brain tumor. Microglia/macrophages are found within human GBM where they likely promote tumor progression. We report that CCL5, CCR1, and CCR5 are expressed in glioblastoma. Individual deletion of CCR1 or CCR5 had little to no effect on survival of tumor bearing mice, or numbers of glioblastoma-infiltrated microglia/macrophages or lymphocytes. CCL5 promoted in vitro migration of wild type, CCR1- or CCR5-deficient microglia/macrophages that w...

  12. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  13. Market News Price Dataset

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Real-time price data collected by the Boston Market News Reporter. The NOAA Fisheries' "Fishery Market News" began operations in New York City on February 14, 1938....

  14. CCR5 as a treatment target in pulmonary arterial hypertension.

    Science.gov (United States)

    Amsellem, Valérie; Lipskaia, Larissa; Abid, Shariq; Poupel, Lucie; Houssaini, Amal; Quarck, Rozenn; Marcos, Elisabeth; Mouraret, Nathalie; Parpaleix, Aurélien; Bobe, Régis; Gary-Bobo, Guillaume; Saker, Mirna; Dubois-Randé, Jean-Luc; Gladwin, Mark T; Norris, Karen A; Delcroix, Marion; Combadière, Christophe; Adnot, Serge

    2014-09-09

    Pulmonary arterial hypertension (PH), whether idiopathic or related to underlying diseases such as HIV infection, results from complex vessel remodeling involving both pulmonary artery smooth muscle cell (PA-SMC) proliferation and inflammation. CCR5, a coreceptor for cellular HIV-1 entry expressed on macrophages and vascular cells, may be involved in the pathogenesis of PH. Maraviroc is a new CCR5 antagonist designed to block HIV entry. Marked CCR5 expression was found in lungs from patients with idiopathic PH, in mice with hypoxia-induced PH, and in Simian immunodeficiency virus-infected macaques, in which it was localized chiefly in the PA-SMCs. To assess the role for CCR5 in experimental PH, we used both gene disruption and pharmacological CCR5 inactivation in mice. Because maraviroc does not bind to murine CCR5, we used human-CCR5ki mice for pharmacological and immunohistochemical studies. Compared with wild-type mice, CCR5-/- mice or human-CCR5ki mice treated with maraviroc exhibited decreased PA-SMC proliferation and recruitment of perivascular and alveolar macrophages during hypoxia exposure. CCR5-/- mice reconstituted with wild-type bone marrow cells and wild-type mice reconstituted with CCR5-/- bone marrow cells were protected against PH, suggesting CCR5-mediated effects on PA-SMCs and macrophage involvement. The CCR5 ligands CCL5 and the HIV-1 gp120 protein increased intracellular calcium and induced growth of human and human-CCR5ki mouse PA-SMCs; maraviroc inhibited both effects. Maraviroc also reduced the growth-promoting effects of conditioned media from CCL5-activated macrophages derived from human-CCR5ki mice on PA-SMCs from wild-type mice. The CCL5-CCR5 pathway represents a new therapeutic target in PH associated with HIV or with other conditions. © 2014 American Heart Association, Inc.

  15. News & Announcements

    Science.gov (United States)

    2000-01-01

    News from Journal House Guidelines for Submission The Journal's current Guide to Submissions can be found on pages 29-30 of this issue. They have been streamlined a bit and also include a handy check list. This information is also available on JCE Online at http://jchemed.chem.wisc.edu/Journal/Authors/. Wanted: Demo Checkers The Tested Demonstrations column needs people who like to try out demos. Column editor Ed Vitz is looking for additional volunteers to serve as "checkers" for manuscripts that have been submitted to the Journal for possible publication as Tested Demonstrations. A checker is expected to perform two functions: to review the manuscript for accuracy and novelty, and to attempt to perform the demonstration according to the procedure supplied by the author. Checkers may suggest important improvements in demonstration procedures, and for their efforts they are cited in the byline when the manuscript is published. For instance, the demo showing the yellow cascading precipitates (lead iodide) made from potassium iodide and lead nitrate was submitted by Wobbe de Vos and checked by Kim Kostka. The (yellow) cascading precipitates are from "Using Large Glass Cylinders To Demonstrate Chemical Reactions" that appeared in the April 1999 issue of JCE. We prefer that checkers begin the review process (which may in some cases involve procuring supplies) very soon after being contacted so that their review can be completed in the timely manner that authors deserve. Checkers are usually teachers who routinely present lecture demonstrations in their classes in either high school or colleges. We try not to call on checkers more often than once a year, which is one of the reasons for this request. Another is that we lose many highly valued, experienced checkers to retirement or other endeavors. Prospective checkers may want to look at a copy of the JCE Tested Demonstration Evaluation Form. It can be found on the Web at http://www.kutztown.edu/ vitz

  16. CCR Interns | Center for Cancer Research

    Science.gov (United States)

    The Cancer Research Interns (CRI) Summer Program was inaugurated in 2004 to provide an open door for students looking for an initial training opportunity. The goal is to enhance diversity within the CCR (Center for Cancer Research) training program and we have placed 338 students from 2004 to 2017, in labs and branches across the division.  The CCR and the Center for Cancer Training’s Office of Training and Education provide stipend support, some Service & Supply funds, and travel support for those students who meet the financial eligibility criteria (

  17. Magnet News

    CERN Multimedia

    Foussat, A; Ruber, R

    Central Solenoid Test The Central Solenoid (CS) and its associated Proximity Cryogenic System have been designed by KEK in collaboration with CERN. Following construction and extensive tests at the Toshiba manufacturing site in Yokohama, Japan, the equipment has been shipped to CERN. The CS is now being prepared for the integration in a common cryostat with the LAr calorimeter, after which a full on-surface test has to be completed before final installation 100m underground in the ATLAS cavern. For this purpose a provisional set-up for the re- commissioning of the final Proximity Cryogenics, the connecting Chimney and the Central Solenoid has been established. During the month of May the Proximity Cryogenics and Chimney with superconducting bus lines have been tested (figure1). The equipment was cooled down to 4.5K and a current of 9000 amperes was applied to the chimney. This is almost 20% above the nominal operational current of 7400 amperes. A number of tests and simulations have been successfully perf...

  18. Computing News

    CERN Multimedia

    McCubbin, N

    2001-01-01

    We are still five years from the first LHC data, so we have plenty of time to get the computing into shape, don't we? Well, yes and no: there is time, but there's an awful lot to do! The recently-completed CERN Review of LHC Computing gives the flavour of the LHC computing challenge. The hardware scale for each of the LHC experiments is millions of 'SpecInt95' (SI95) units of cpu power and tens of PetaBytes of data storage. PCs today are about 20-30SI95, and expected to be about 100 SI95 by 2005, so it's a lot of PCs. This hardware will be distributed across several 'Regional Centres' of various sizes, connected by high-speed networks. How to realise this in an orderly and timely fashion is now being discussed in earnest by CERN, Funding Agencies, and the LHC experiments. Mixed in with this is, of course, the GRID concept...but that's a topic for another day! Of course hardware, networks and the GRID constitute just one part of the computing. Most of the ATLAS effort is spent on software development. What we ...

  19. News & Announcements

    Science.gov (United States)

    1999-08-01

    News from Journal House Perspective on JCE Online Recently a reader asked us for a perspective on JCE Onlinehow the chemical education community is receiving it and how the Journal staff itself views it. We share our responses below. Subscriber Numbers How many people subscribe to JCE Online+? As of June 1, 1999, our records show that 13% of individual JCE subscriptions in the USA include JCE Online+. This percentage has increased significantly during the past year- in June 1998 it was approximately 4% and December 1998 about 7%. Almost all subscribers to JCE Online subscribe to print as well. Since JCE Online has only very recently been made available to institutional subscribers, there are no numbers to report. There has been considerable interest in online from libraries. Given that JCE Online+ is a fairly recent subscriber option and that many subscribers have a wait-and-see approach to any new option, we feel that the numbers above are quite high. The steady growth is encouraging. Online Usage How many people visit our Web site? Statistics for the period January 1, 1999, through May 31, 1999, that may be of interest include: Total Pages Served 361,115 Total Visits 138,377 Total Unique Visitors 51,744 Total Repeat Visitors 11,536 Average Visit Length 03:05 Average Requests/Visit 10.8 Average Pages/Visit 2.6 Average Daily Visits 916 Online Rationale and Expectations JCE Online is a very important part of the whole Journal, but we do not expect it to supplant print: online and print are very different media. Usage of JCE Online is growing steadily; our subscribers are realizing what we have learned: it is not possible to deliver the Journal in the print medium alone- print is no longer adequate to accomplish our mission. Examples of things not possible in print include: ·JCE Index to all 76 years of Journal issues, available all the time with responses within seconds. ·Supplementary materials that are important to only a limited number of our subscribers

  20. Who Makes The News?

    DEFF Research Database (Denmark)

    Jørndrup, Hanne; Bentsen, Martine

    -running and most extensive research on gender in the news media. It began in 1995 when volunteers in 71 countries around the world monitored women’s presence in their national radio, television and print news. The research revealed that only 17% of news subjects – the people who are interviewed or whom the news...... is about – were women. It found that gender parity was ‘a distant prospect in any region of the world. News [was] more often being presented by women but it [was] still rarely about women. Denmark participates in GMMP for the second time and both times we can recognize the global inequality in the Danish...... media. In 2010 women made up 31 % of the news subjects compared to the global average of 24 % women. This year the share of women in news has declined to 25% so Denmark is almost on level with the global average....

  1. Anatomy of news consumption on Facebook.

    Science.gov (United States)

    Schmidt, Ana Lucía; Zollo, Fabiana; Del Vicario, Michela; Bessi, Alessandro; Scala, Antonio; Caldarelli, Guido; Stanley, H Eugene; Quattrociocchi, Walter

    2017-03-21

    The advent of social media and microblogging platforms has radically changed the way we consume information and form opinions. In this paper, we explore the anatomy of the information space on Facebook by characterizing on a global scale the news consumption patterns of 376 million users over a time span of 6 y (January 2010 to December 2015). We find that users tend to focus on a limited set of pages, producing a sharp community structure among news outlets. We also find that the preferences of users and news providers differ. By tracking how Facebook pages "like" each other and examining their geolocation, we find that news providers are more geographically confined than users. We devise a simple model of selective exposure that reproduces the observed connectivity patterns.

  2. News & Announcements

    Science.gov (United States)

    2000-02-01

    News from Journal House Journal Ambassadors, 1999 What do the people listed below have in common? A search of our records indicates that each has been a participant in our Journal Ambassador program during 1999. Guy Anderson Jim Becvar Jerry Bell Jim Birk Diane Bunce Ann Cartwright Thomas Clark Jane Crosby Maria Dean Art Ellis Donald Elswick Tommy Franklin Babu George Paul Heath Angela Hoffman Lynn Hogue J. J. Lagowski Frank Lambert Dorothy Lehmkuhl George Lelevre Scott Luaders Jane McMullen Marci Merritt Carl Minnier Richard Narske Ron Perkins Gabriel Pinto Dick Potts Herb Retcofsky Jerry Sarquis Elke Schoffers Sara Selfe Uni Susskind J. Mark Tolman John Varine Dawn Wakeley Marla White Those who are a part of this program take materials about the Journal to workshops, outreach programs, seminars, regional meetings, award nights, short courses, and other events at home and abroad, places where people who are interested in chemical education gather. Given about three weeks notice, we can outfit you with a variety of materials that will help others get tuned in to the good things that are happening in chemical education. We can send you an assortment of Journal issues, subscription forms, our Publications/Software Catalog, reprints from the Viewpoints series, copies of Classroom Activities, or JCE Gift Award Certificates, assuming that supplies are available. Of course we can arrange for the group to have temporary access to JCE Online. We can send you a brochure about the Ambassador program or answer any questions - just ask: email to jce@chem.wisc.edu; phone 1-800-991-5534 (U.S.) or 608-262-5153 (non-U.S.); fax 608-265-8094. If by chance you were a Journal Ambassador in 1999 but your name was not included, just let us know so that you can be recognized in a future column. Gift Subscription Awards As spring, the season of awards, approaches, we remind you of our handy Gift Certificates (a replica is shown on page 142). A gift of the Journal is not only affordable

  3. Naturally Occurring Deletional Mutation in the C-Terminal Cytoplasmic Tail of CCR5 Affects Surface Trafficking of CCR5

    OpenAIRE

    Shioda, Tatsuo; Nakayama, Emi E.; Tanaka, Yuetsu; Xin, Xiaomi; Liu, Huanliang; Kawana-Tachikawa, Ai; Kato, Atsushi; Sakai, Yuko; Nagai, Yoshiyuki; Iwamoto, Aikichi

    2001-01-01

    CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(−) is a single-nucleotide deletion mutation which is observed exclusively in Asians (M. A. Ansari-Lari, et al., Nat. Genet. 16:221–222, 1997). This mutant gene produces a CCR5 which lacks the entire C-terminal cytoplasmic tail. To assess the effect of CCR5-893(−) on HIV-1 infection, we generated a recombinant Sendai virus expressing the mutant CCR5 and compared its HIV...

  4. Institute news

    Science.gov (United States)

    1999-11-01

    celebrate the Group's 50th anniversary by examining what has been done, focusing on why and how it was done, with lessons and ambitions for the future. The meeting will be held at Institute Headquarters and the programme is as follows: 10.45 - 11.00 Welcome and introduction (Philip Britton: Chair of the Education Group) 11.00 - 11.45 Examinations and assessment through the ages (Tim Akrill, Chief Examiner for A-level Physics with Edexcel) 11.45 - 12.30 Curriculum reform in physics, past, present and future (Professor Jon Ogborn, Director of the Post-16 Physics Initiative) 14.00 - 14.15 Physics education and the Institute of Physics, some personal reflections (speaker to be announced) 14.15 - 15.00 Connecting with Advancing Physics: the first year in HE physics (Professor Mick Brown, University of Cambridge) 15.15 - 15.35 Physics education, the next 50 years! (Ken Dobson, Honorary Editor of Physics Education) The day should hold something for everyone, so reserve your place if you can. Schools and Colleges lecture Dr Zbig Sobiesierski of the University of the West of England is the 1999 - 2000 Institute of Physics Schools and Colleges lecturer, touring the country with his talk `Seeing is believing?'. He will demonstrate the different physical ways in which we can both make and mix colour and will then proceed to discuss why our eyes respond to light in the way they do. The lecture will be aimed primarily at students aged 14 and above, but it will also be suitable for older audiences. The intention, as with previous series, will be to show the relevance of the physics concepts to the members of the audience and the world in which they live. To find out more about the lecture in your area and to make a booking, contact should be made with the local organizer (full details of the list can be obtained from Catherine Wilson at Institute Headquarters). The dates and venues planned so far are as follows: 1 Nov: Northern College, Aberdeen 2 Nov: University of St Andrews 3 Nov

  5. The Abrogation of Phosphorylation Plays a Relevant Role in the CCR5 Signalosome Formation with Natural Antibodies to CCR5

    Directory of Open Access Journals (Sweden)

    Assunta Venuti

    2017-12-01

    Full Text Available The exposure to CCR5 (CC chemokine receptor 5 specific natural antibodies in vitro produces a Class B β-arrestin2-dependent CCR5 retention with the aid of ERK1, due to the formation of a CCR5 signalosome, which remains stable for at least 48 h. Considering that β-arrestins and MAPKs are receptive to environmental signals, their signal complexes could be one of the key junction for GPCRs internalization related signal transduction. Here, we demonstrate that, in T cells, the phosphorylation status of either CCR5 receptor or ERK1 protein is necessary to drive the internalized receptor into the early endosomes, forming the CCR5 signalosome. In particular, our data show that β-arrestin2/ERK1 complex is a relevant transducer in the CCR5 signaling pathway. Understanding the mechanism of CCR5 regulation is essential for many inflammatory disorders, tumorigenesis and viral infection such as HIV.

  6. Routinizing Breaking News

    DEFF Research Database (Denmark)

    Hartley, Jannie Møller

    2011-01-01

    This chapter revisits seminal theoretical categorizations of news proposed three decades earlier by US sociologist Gaye Tuchman. By exploring the definition of ”breaking news” in the contemporary online newsrooms of three Danish news organisations, the author offers us a long overdue re......-theorization of journalistic practice in the online context and helpfully explores well-evidenced limitations to online news production, such as the relationship between original reporting and the use of ”shovelware.”...

  7. Multilingual News Article Classification

    OpenAIRE

    Skjennum, Patrick L

    2016-01-01

    News is an ever-growing and global resource, reliant on robust distribution networks to spread information. This thesis investigates how exploiting semantic, contextual and ontological information may form a basis for a language independent news article classification system. In light of the above, a scalable multi-label news article classification system, based exclusively on extracted DBpedia entities, and a predetermined standardized set of fixed-size IPTC Media Topic categories, is p...

  8. The news Engine

    DEFF Research Database (Denmark)

    Andersson, Ralf

    platforms. It discusses challengesof new practices of news production, cross-media reporting and mediaconvergence, resulting from DR’s new experiment, the news engine – with differentaspects: Product: The main news program 6:30 has fewer stories, but each one has moreelements. It’s not just one single pre...... is producedby many reporters. -      Technological change/new technicalskills: in relation to recording and editing with the latest equipment andhaving the ability to integrate and understand new and fast-changing technicalworkflows.   Changes in DR News are already an inspiration for many other TV newsstations...

  9. Owl monkey CCR5 reveals synergism between CD4 and CCR5 in HIV-1 entry.

    Science.gov (United States)

    Nahabedian, John; Sharma, Amit; Kaczmarek, Maryska E; Wilkerson, Greg K; Sawyer, Sara L; Overbaugh, Julie

    2017-12-01

    Studying HIV-1 replication in the presence of functionally related proteins from different species has helped define host determinants of HIV-1 infection. Humans and owl monkeys, but not macaques, encode a CD4 receptor that permits entry of transmissible HIV-1 variants due to a single residue difference. However, little is known about whether divergent CCR5 receptor proteins act as determinants of host-range. Here we show that both owl monkey (Aotus vociferans) CD4 and CCR5 receptors are functional for the entry of transmitted HIV-1 when paired with human versions of the other receptor. By contrast, the owl monkey CD4/CCR5 pair is generally a suboptimal receptor combination, although there is virus-specific variation in infection with owl monkey receptors. Introduction of the human residues 15Y and 16T within a sulfation motif into owl monkey CCR5 resulted in a gain of function. These findings suggest there is cross-talk between CD4 and CCR5 involving the sulfation motif. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The News Delivery Sequence: Bad News and Good News in Conversational Interaction.

    Science.gov (United States)

    Maynard, Douglas W.

    1997-01-01

    Explores the conditional nature of good and bad news while focusing on three topics: (1) the status of information as news according the participants in a conversation; (2) the valence of this information with regard to its perception as good or bad; and (3) the effect of news on individuals. Notes that good news is privileged over bad news in…

  11. CCR5 inhibitors in HIV-1 therapy.

    Science.gov (United States)

    Dorr, Patrick; Perros, Manos

    2008-11-01

    The human immunodeficiency virus 1 (HIV-1) is the causative pathogen of AIDS, the world's biggest infectious disease killer. About 33 million people are infected worldwide, with 2.1 million deaths a year as a direct consequence. The devastating nature of AIDS has prompted widespread research, which has led to an extensive array of therapies to suppress viral replication and enable recovery of the immune system to prolong and improve patient life substantially. However, the genetic plasticity and replication rate of HIV-1 are considerable, which has lead to rapid drug resistance. This, together with the need for reducing drug side effects and increasing regimen compliance, has led researchers to identify antiretroviral drugs with new modes of action. This review describes the discovery and clinical development of CCR5 antagonists and the recent approval of maraviroc as a breakthrough in anti-HIV-1 therapy. CCR5 inhibitors target a human cofactor to disable HIV-1 entry into the cells, and thereby provide a new hurdle for the virus to overcome. The status and expert opinion of CCR5 antagonists for the treatment of HIV-1 infection are detailed.

  12. Brazilian news portals characteristics

    Directory of Open Access Journals (Sweden)

    Heloiza G. Herckovitz

    2009-06-01

    Full Text Available A content analysis of four Brazilian news media portals found that economic news dominated the top headlines with little attention paid to education, the environment and welfare. Other trends included a focus on local events and national news sources, reliance on few sources, mostly official ones, and a low percentage of news that fitted the concept of newsworthiness (a combination of both social significance and deviance concepts. Other findings of a study of 432 top news stories published by UOL, Estadão, iG and Terra during a 15-day period between February and March 2008 indicate that the top portions of the portals’ front pages carry news that lacks story depth, editorial branding, and multimedia applications. The results suggest that online news portals are in their infancy although Brazil has the largest online population of Latin America. This study hopes to shed light on the gatekeeping process in Brazilian news portals. Brazilian media portals have yet to become a significant editorial force able to provide knowledge about social issues and public affairs in a socially responsible fashione.

  13. BRAZILIAN NEWS PORTALS CHARACTERISTICS

    Directory of Open Access Journals (Sweden)

    Heloiza G. Herckovitz

    2011-02-01

    Full Text Available A content analysis of four Brazilian news media portals found that economic news dominated the top headlines with little attention paid to education, the environment and welfare. Other trends included a focus on local events and national news sources, reliance on few sources, mostly official ones, and a low percentage of news that fitted the concept of newsworthiness (a combination of both social significance and deviance concepts. Other findings of a study of 432 top news stories published by UOL, Estadão, iG and Terra during a 15-day period between February and March 2008 indicate that the top portions of the portals’ front pages carry news that lacks story depth, editorial branding, and multimedia applications. The results suggest that online news portals are in their infancy although Brazil has the largest online population of Latin America. This study hopes to shed light on the gatekeeping process in Brazilian news portals. Brazilian media portals have yet to become a significant editorial force able to provide knowledge about social issues and public affairs in a socially responsible fashione.

  14. The news Engine

    DEFF Research Database (Denmark)

    Andersson, Ralf

    The News Engine How a new experiment in newsrooms can change process, product and people.   By Ralf Andersson   In fall 2012, the news department of the Danish Broadcasting Corporation,decided to implement a new workflow called ”The News Engine” - in order to workfaster, more freely, flexible and...... in Europe, who are implementing the news engine as workflow.   This challenges us to rethink and reconsider new practices of newproduction, potentialities and experimentations.  ......The News Engine How a new experiment in newsrooms can change process, product and people.   By Ralf Andersson   In fall 2012, the news department of the Danish Broadcasting Corporation,decided to implement a new workflow called ”The News Engine” - in order to workfaster, more freely, flexible...... and with fewer resources. This was done to raisethe productivity. The fundamental principle was that all stories should fit all platforms(content sharing) - and that no one did their own story anymore. DR News introduced 8-10 mobile live teams who are responsible for doinginterviews, record pictures and sound...

  15. News Story Quotes: Verbatim?

    Science.gov (United States)

    Davenport, Lucinda

    A study determined what beginning journalists and news reporting students have learned is acceptable to quote, verbatim, in a news story, and where they learned about these guidelines. Results of a questionnaire given to journalism students indicated that most would change direct quotes by adjusting blasphemies, correcting faulty grammar, cleaning…

  16. Analysis of Staphylococcal cassette chromosome mec in Staphylococcus haemolyticus and Staphylococcus sciuri: identification of a novel ccr gene complex with a newly identified ccrA allotype (ccrA7).

    Science.gov (United States)

    Urushibara, Noriko; Paul, Shyamal Kumar; Hossain, Mohammad Akram; Kawaguchiya, Mitsuyo; Kobayashi, Nobumichi

    2011-06-01

    Methicillin resistance in staphylococci is conferred by the acquisition in its chromosome of the mecA gene, which is located on a mobile genetic element called staphylococcal cassette chromosome mec (SCCmec). Genetic type of SCCmec is defined by combination of mec gene complex class and cassette chromosome recombinase gene (ccr) allotype. In this study, we analyzed genetic diversity of the SCCmec in 11 Staphylococcus haemolyticus strains and a Staphylococcus sciuri strain, which were recently isolated from clinical specimens in Bangladesh. Among these strains, only two S. haemolyticus strains were proved to have the known types of SCCmec, that is, SCCmec V (class C2 mec-ccrC) and VII (class C1 mec-ccrC). Five S. haemolyticus strains were assigned two unique mec-ccr gene complexes combination; that is, class C1 mec-ccrA4B4 (four isolates) and class A mec-ccrC (one isolate). In the remaining four S. haemolyticus strains with class C1 mec, no known ccr allotypes could be detected. A single S. sciuri strain with class A mec complex carried a ccrA gene belonging to a novel allotype designated ccrA7, together with ccrB3. The ccrA7 gene in the S. sciuri strain showed 61.7%-82.7% sequence identity to the ccrA gene sequences published so far, and 75.3% identity to ccrA3, which is a component of the type 3 ccr complex (ccrA3-ccrB3) in methicillin-resistant Staphylococcus aureus. The results of the present study indicated that mec gene complex and ccr genes in coagulase-negative staphylococci are highly divergent, and distinct from those of common methicillin-resistant S. aureus. Identification of the novel ccrA7 allotype combined with ccrB3 suggested an occurrence of recombination between different ccr complexes in nature.

  17. Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE

    Directory of Open Access Journals (Sweden)

    Ericsson-Dahlstrand Anders

    2007-05-01

    Full Text Available Abstract Background The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS in multiple sclerosis (MS and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE. While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions. Methods The expression of CCR1, CCR2 and CCR5 mRNA was studied with in situ hybridization using radio labelled cRNA probes in combination with immunohistochemical staining for phenotypic cell markers. Spinal cord sections from healthy rats and rats with MOG-EAE (acute phase, remission phase, relapse phase were analysed. In defined lesion stages, the number of cells expressing CCR1, CCR2 and CCR5 mRNA was determined. Data were statistically analysed by the nonparametric Mann-Whitney U test. Results In MOG-EAE rats, extensive up-regulation of CCR1 and CCR5 mRNA, and moderate up-regulation of CCR2 mRNA, was found in the spinal cord during episodes of active inflammation and demyelination. Double staining with phenotypic cell markers identified the chemokine receptor mRNA-expressing cells as macrophages/microglia. Expression of all three receptors was substantially reduced during clinical remission, coinciding with diminished inflammation and demyelination in the spinal cord. Healthy control rats did not show any detectable expression of CCR1, CCR2 or CCR5 mRNA in the spinal cord. Conclusion Our results demonstrate that the acute and chronic-relapsing phases of MOG

  18. Sharing good NEWS across the world: developing comparable scores across 12 countries for the neighborhood environment walkability scale (NEWS)

    Science.gov (United States)

    2013-01-01

    subscale was highly, while the Australian and Belgian versions were marginally, comparable to the standard version. Single-item versions of the Street connectivity subscale used in Australia and Belgium showed marginally acceptable correspondence to the standard version. Conclusions We have proposed country-specific modifications to the original scoring protocol of the NEWS/NEWS-A that enhance inter-country comparability. These modifications have yielded sufficiently equivalent measurement models of the NEWS/NEWS-A. Some inter-country discrepancies remain. These need to be considered when interpreting findings from different countries. PMID:23566032

  19. Tweeting News Articles

    Directory of Open Access Journals (Sweden)

    Marco Toledo Bastos

    2013-09-01

    Full Text Available In this article we investigate the impact of social media readership to the editorial profile of newspapers. We analyze tweets containing links to news articles from eight of the largest national newspapers in the United States, United Kingdom, Spain, Brazil, and Germany. The data collection follows the first two weeks of October 2012 and includes 2,842,699 tweets with links to news articles. Twitter-shortened links were resolved using a three-pass routine and assigned to 1 of the 21 newspaper sections. We found the concentration of links to news articles posted by top users to be lower than reported in the literature and the strategy of relaying headlines on Twitter via automatic news aggregators (feeds to be inefficient. The results of this investigation show which sections of a newspaper are the most and least read by readers in different parts of the world, with German readers placing greater emphasis on Politics and Economy; Brazilians on Sports and Arts; Spaniards on Local and National news; Britons and Americans on Opinion and World news. We also found that German and Spanish readers are more likely to read multiple national newspapers, while British readers more often resort to foreign sources of news. The results confirm that feedback to news items from a large user base is pivotal for the replication of content and that newspapers and news items can be clustered according to the editorial profile and principles of newsworthiness inherited from legacy media. The results of this investigation shed light onto the networked architecture of journalism that increasingly depends on readership agency.

  20. Cascading Corruption News

    DEFF Research Database (Denmark)

    Damgaard, Mads

    2018-01-01

    Through a content analysis of 8,800 news items and six months of front pages in three Brazilian newspapers, all dealing with corruption and political transgression, this article documents the remarkable skew of media attention to corruption scandals. The bias is examined as an information...... phenomenon, arising from systemic and commercial factors of Brazil’s news media: An information cascade of news on corruption formed, destabilizing the governing coalition and legitimizing the impeachment process of Dilma Rousseff. As this process gained momentum, questions of accountability were disregarded...... by the media, with harmful effects on democracy....

  1. Cascading Corruption News

    DEFF Research Database (Denmark)

    Damgaard, Mads

    2018-01-01

    Through a content analysis of 8,800 news items and six months of front pages in three Brazilian newspapers, all dealing with corruption and political transgression, this article documents the remarkable skew of media attention to corruption scandals. The bias is examined as an information...... phenomenon, arising from systemic and commercial factors of Brazil’s news media: An information cascade of news on corruption formed, destabilizing the governing coalition and legitimizing the impeachment process of Dilma Rousseff. As this process gained momentum, questions of accountability were disregarded...

  2. Grape seed extract proanthocyanidins downregulate HIV- 1 entry coreceptors, CCR2b, CCR3 and CCR5 gene expression by normal peripheral blood mononuclear cells

    Directory of Open Access Journals (Sweden)

    MADHAVAN P NAIR

    2002-01-01

    Full Text Available Flavonoids and related polyphenols, in addition to their cardioprotective, anti-tumor, anti-inflammatory, anti-carcinogenic and anti-allergic activities, also possess promising anti-HIV effects. Recent studies documented that the ß-chemokine receptors, CCR2b, CCR3 and CCR5, and the alpha-chemokine receptors, CXCR1, CXCR2 and CXCR4 serve as entry coreceptors for HIV-1. Although flavonoids and polyphenolic compounds elicit anti-HIV effects such as inhibition of HIV-1 expression and virus replication, the molecular mechanisms underlying these effects remain to be clearly elucidated. We hypothesize that flavonoids exert their anti-HIV effects, possibly by interfering at the HIV co-receptor level. We investigated the effect of flavonoid constituents of a proprietary grape seed extract (GSE on the expression of HIV-1 coentry receptors by immunocompetent mononuclear leukocytes. Our results showed that GSE significantly downregulated the expression of the HIV-1 entry co-receptors, CCR2b , CCR3 and CCR5 in normal PBMC in a dose dependent manner. Further , GSE treated cultures showed significantly lower number of CCR3 positive cells as quantitated by flow cytometry analysis which supports RT-PCR gene expression data.Investigations of the mechanisms underlying the anti-HIV-1 effects of grape seed extracts may help to identify promising natural products useful in the prevention and /or amelioration of HIV-1 infection

  3. Compact containment boiling water reactor (CCR)

    International Nuclear Information System (INIS)

    2006-01-01

    The compact containment boiling water reactor (CCR) is a modular boiling water reactor (BWR) designed by the Toshiba Corporation with the support of the Japan Atomic Power Company (JAPC). The current CCR design falls into the category of innovative small and medium size reactors, featuring 300MW electrical output per module. In Japan, increases in nuclear plant unit capacity have been promoted to take advantage of the economies of scale while further enhancing safety and reliability. As a result, more than 50 nuclear units are playing an important role in the domestic electric power generation. The next generation reactor with a 1700 MW(e) capacity is currently under development [IX-1, IX-2]. However, the future of nuclear power generation looks uncertain because of increasing competition with other power sources [IX-3] in the deregulated market, in spite of the general recognition that nuclear power is attractive from the viewpoint of energy security and environmental protection. Furthermore, factors such as stagnant growth in recent electricity demand, limitations in grid capacity and limited initial investment to avoid risk, will not favour large plant outputs. Nuclear plants are required that can easily be adopted in any country to globalize nuclear power generation for the mitigation of greenhouse effects. In the 1980s, the Toshiba Corporation has carried out R and D for BWRs with natural circulation and passive safety features. These R and D included tests and analysis of passive containment cooling systems (PCCS), isolation condensers (IC) and gravity driven cooling systems (GDCS). The results obtained through these tests have been used in the design of a simplified boiling water reactor (SBWR). Based on these activities, the design of a simplified BWR with a long operating cycle (LSBWR) design has been under development since the mid 1990s. The concept of the LSBWR is to provide flexibility to meet site conditions and electricity demands, to mitigate

  4. Is Crime News Coverage Excessive?

    Science.gov (United States)

    Graber, Doris A.

    1979-01-01

    Reports on the frequency and manner in which various crime and noncrime news topics were presented in selected newspapers and television newscasts in 1976. Examines news flow data to determine whether news output was inflexible, and whether crime news coverage distorted the amount of real-life crime. (PD)

  5. On relativistic irreducible quantum fields fulfilling CCR

    International Nuclear Information System (INIS)

    Baumann, K.

    1987-01-01

    Let phi be a relativistic scalar field fulfilling canonical commutation relations (CCR). Furthermore it is assumed that the time zero fields and momenta form an irreducible set. Based on estimates given by Herbst [I. W. Herbst, J. Math. Phys. 17, 1210 (1976)], and by methods developed by Powers [R. T. Powers, Commun. Math. Phys. 4, 145 (1967)], it is shown that phi has to be a free field in n>3 space dimensions. For n = 3 (resp. n = 2) restrictions that look similar to the restriction in a formal :phi 4 : 3 /sub +/ 1 (resp. :phi 6 : 2 /sub +/ 1 ) theory are obtained

  6. Zimbabwe Science News

    African Journals Online (AJOL)

    -disciplinary and semi-popular. The Zimbabwe Science News has ceased publication. ... An overview of solar and solar-related technologies in Zimbabwe · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL ...

  7. Breaking News as Radicalisation

    DEFF Research Database (Denmark)

    Hartley, Jannie Møller

    provides us with the following two research questions: How does the category of breaking news fit into Tuchmans typology related to time, planning and technology? What types of stories are providing journalistic capital and how are online news stories categorised relatively within the journalistic field?......The aim of the paper is to make explicit how the different categories are applied in the online newsroom and thus how new categories can be seen as positioning strategies in the form of radicalisations of already existing categories. Thus field theory provides us with tools to analyse how online...... journalists are using the categorisations to create hierarchies within the journalistic field in order to position themselves as specialists in what Tuchman has called developing news, aiming and striving for what today is know as breaking news and the “exclusive scoop,” as the trademark of online journalism...

  8. Prostate Cancer Foundation News

    Science.gov (United States)

    ... and getting big traps, six-pack abs and “gun show” biceps, your prostate would like to disagree. ... Guides Receive PCF news in your inbox Spam Control Text: Please leave this field empty EIN #95- ...

  9. Television News as Rhetoric

    Science.gov (United States)

    Smith, Craig R.

    1977-01-01

    Contends that television is a pre-eminent source of persuasion in American today and examines the television news reporting strategies that have succeeded in contributing to televisions persuasive impact. (MH)

  10. The News Media Industry

    National Research Council Canada - National Science Library

    Bartlett, Charlie

    2003-01-01

    American news media has two fundamental roles in our democracy: that of eyewitness, giving citizens critical information, and also as the watchdog, providing another arm of "checks and balances" within our governmental system...

  11. CCG - News & Events

    Science.gov (United States)

    NCI's Center for Cancer Genomics (CCG) has been widely recognized for its research efforts to facilitiate advances in cancer genomic research and improve patient outcomes. Find the latest news about and events featuring CCG.

  12. The News Media Industry

    Science.gov (United States)

    2003-06-05

    international news, consolidation, government deregulation, coverage of national security issues, “ infotainment ,” and the “digital revolution.” In...interest in international news, consolidation, government deregulation, coverage of national security issues, “ infotainment ,” and the “digital...tool in pursuing US national security interests into the 21st century. Growing Impact of “ Infotainment ” “ Infotainment ” is the

  13. CCR presentations at AACR - 2018 | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Chicago, IL, between April 14-18, 2018. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  14. CCR presentations at AACR | Center for Cancer Research

    Science.gov (United States)

    CCR presentations at AACR Several CCR scientists will present their research at the AACR Annual Meeting in Washington, D.C., between April 1-5, 2017. Selected oral presentations are listed below. A full list of abstracts can be found on the AACR website.

  15. A Simplified Technique for Evaluating Human "CCR5" Genetic Polymorphism

    Science.gov (United States)

    Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda

    2013-01-01

    To involve students in thinking about the problem of AIDS (which is important in the view of nondecreasing infection rates), we established a practical lab using a simplified adaptation of Thomas's (2004) method to determine the polymorphism of HIV co-receptor CCR5 from students' own epithelial cells. CCR5 is a receptor involved in inflammatory…

  16. Chemokine receptor CCR5 in interferon-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Kristiansen, T B; Wittenhagen, P

    2007-01-01

    To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta).......To study the relationship between CC chemokine receptor CCR5 expression and disease activity in multiple sclerosis (MS) patients treated with beta-interferon (IFN-beta)....

  17. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

  18. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  19. The ins and outs of ligand binding to CCR2

    NARCIS (Netherlands)

    Zweemer, Annelien Jacomina Maria

    2014-01-01

    This thesis provides novel insights in the molecular mechanism of action of antagonists for the chemokine receptor CCR2. CCR2 belongs to the protein family of G protein-coupled receptors (GPCRs). It is involved in several inflammatory diseases and therefore many small molecule antagonists targeting

  20. Metal dusting in CCR platforming unit

    Energy Technology Data Exchange (ETDEWEB)

    Dampc, J. [Lotos Group SA, Gdansk (Poland); Grzesik, Z. [AGH University of Science and Technology, Krakow (Poland); Hucinska, J. [Gdansk University of Technology, Gdansk (Poland)

    2009-03-15

    The mechanism of metal dusting of 9Cr-1Mo steel in CCR platforming unit, based on examinations of a charge heater tube, is presented. The tube operated for 10 years, and the metal skin temperature was about 600 C. The feed was composed of hydrotreated naphtha and hydrogen gas. The mechanism of the corrosion was elucidated using scanning electron microscopy, electron probe microanalysis and X-ray diffraction technique. It has been found that the carbon deposition on the steel surface and its inward diffusion into the steel is accompanied by the outward diffusion of carbide forming elements, i.e. chromium and molybdenum. At an advanced stage of the metal dusting process a thin layer of fine chromium-rich carbides beneath the steel surface exists. The layer is followed by a porous zone composed of big degraded primary carbides and fine carbides instead of alloy ferrite, with chromium and molybdenum content higher than the ferrite inside the tube wall. On the steel surface, a layer of coke composed of graphite, iron and M{sub 7}C{sub 3} carbides is formed and the uniform wastage of the steel takes place. Possible influence of some sulphur additions to the CCR platformer feed during the future service on degradation of the subsurface material has been considered. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  1. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C

    2011-01-01

    molecules often act more deeply in an allosteric mode. However, opposed to the well described molecular interaction of allosteric modulators in class C 7-transmembrane helix (7TM) receptors, the interaction in class A, to which the chemokine receptors belong, is more sparsely described. Using the CCR5...... chemokine receptor as a model system, we studied the molecular interaction and conformational interchange required for proper action of various orthosteric chemokines and allosteric small molecules, including the well known CCR5 antagonists TAK-779, SCH-C, and aplaviroc, and four novel CCR5 ago......-allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...

  2. CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites of infection

    DEFF Research Database (Denmark)

    Nansen, A; Marker, O; Bartholdy, C

    2000-01-01

    Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic choriomeningi......Chemokines and their receptors play a critical role in the selective recruitment of various leukocyte subsets. In this study, we correlated the expression of multiple chemokine and CC chemokine receptor (CCR) genes during the course of intracerebral (i.c.) infection with lymphocytic...... a rapidly lethal, T cell-independent encephalitis, and infection resulted in a dramatic early up-regulation of chemokine gene expression. Similar marked up-regulation of chemokine expression was not seen until late after LCMV infection and required the presence of activated T cells. Cerebral CCR gene...... expression was dominated by CCR1, CCR2 and CCR5. However, despite a stronger initial chemokine signal in VSV-infected mice, only LCMV-induced T cell-dependent inflammation was found to be associated with substantially increased expression of CCR genes. Virus-activated CD8+ T cells were found to express CCR2...

  3. Systemic MCP1/CCR2 blockade and leukocyte specific MCP1/CCR2 inhibition affect aortic aneurysm formation differently

    NARCIS (Netherlands)

    de Waard, Vivian; Bot, Ilze; de Jager, Saskia C. A.; Talib, Sara; Egashira, Kensuke; de Vries, Margreet R.; Quax, Paul H. A.; Biessen, Erik A. L.; van Berkel, Theo J. C.

    2010-01-01

    Objective: CCR2, the receptor for monocyte chemoattractant protein 1 (MCP1), is involved in atherosclerosis and abdominal aortic aneurysms (AAAs). Here, we explored the potential beneficial blockade of the MCP1/CCR2 pathway. Methods: We applied an AAA model in aging apolipoprotein E deficient mice

  4. Role of the chemokine receptors CCR1, CCR2 and CCR4 in the pathogenesis of experimental dengue infection in mice.

    Directory of Open Access Journals (Sweden)

    Rodrigo Guabiraba

    Full Text Available Dengue virus (DENV, a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1⁻/⁻ mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2⁻/⁻ mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4⁻/⁻ mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection.

  5. News values on social media: News organizations' Facebook use.

    Science.gov (United States)

    Al-Rawi, Ahmed

    2017-08-01

    This study examines the news selection practices followed by news organizations through investigating the news posted on social networking sites and, in particular, the Facebook pages of four foreign Arabic language TV stations: The Iranian Al-Alam TV, Russia Today, Deutsche Welle, and BBC. A total of 15,589 news stories are analyzed in order to examine the prominence of references to countries and political actors. The study reveals that social significance and proximity as well as the news organizations' ideological agenda are the most important elements that dictate the news selection process.

  6. News values on social media: News organizations’ Facebook use

    Science.gov (United States)

    Al-Rawi, Ahmed

    2016-01-01

    This study examines the news selection practices followed by news organizations through investigating the news posted on social networking sites and, in particular, the Facebook pages of four foreign Arabic language TV stations: The Iranian Al-Alam TV, Russia Today, Deutsche Welle, and BBC. A total of 15,589 news stories are analyzed in order to examine the prominence of references to countries and political actors. The study reveals that social significance and proximity as well as the news organizations’ ideological agenda are the most important elements that dictate the news selection process. PMID:29278253

  7. Chemokine CCL28 induces apoptosis of decidual stromal cells via binding CCR3/CCR10 in human spontaneous abortion.

    Science.gov (United States)

    Sun, Chan; Zhang, Yuan-Yuan; Tang, Chuan-Ling; Wang, Song-Cun; Piao, Hai-Lan; Tao, Yu; Zhu, Rui; Du, Mei-Rong; Li, Da-Jin

    2013-10-01

    Spontaneous abortion is the most common complication of pregnancy. Immune activation and the subsequent inflammation-induced tissue injury are often observed at the maternal-fetal interface as the final pathological assault in recurrent spontaneous abortion. However, the precise mechanisms responsible for spontaneous abortion involving inflammation are not fully understood. Chemokine CCL28 and its receptors CCR3 and CCR10 are important regulators in inflammatory process. Here, we examined the expression of CCL28 and its receptors in decidual stromal cells (DSCs) by immunochemistry and flow cytometry (FCM), and compared their expression level in DSCs from normal pregnancy versus spontaneous abortion, and their relationship to inflammatory cytokines production by DSCs. We further analyzed regulation of the pro-inflammatory cytokines on CCL28 expression in DSCs by real-time polymerase chain reaction, In-cell Western and FCM. The effects of CCL28-CCR3/CCR10 interaction on DSC apoptosis was investigated by Annexin V staining and FCM analysis or DAPI staining and nuclear morphology. Higher levels of the inflammatory cytokines interleukin (IL)-1β, IL-17A and tumor necrosis factor-α, and increased CCR3/CCR10 expression were observed in DSCs from spontaneous abortion compared with normal pregnancy. Treatment with inflammatory cytokines differently affected CCL28 and CCR3/CCR10 expression in DSCs. Human recombinant CCL28 promoted DSC apoptosis, which was eliminated by pretreatment with neutralizing antibodies against CCR3/CCR10 and CCL28. However, CCL28 did not affect DSC growth. These results suggest that the inflammation-promoted up-regulation of CCL28 and its receptors interaction in DSCs is involved in human spontaneous abortion via inducing DSC apoptosis.

  8. Editing CCR5: a novel approach to HIV gene therapy.

    Science.gov (United States)

    Cornu, Tatjana I; Mussolino, Claudio; Bloom, Kristie; Cathomen, Toni

    2015-01-01

    Acquired immunodeficiency syndrome (AIDS) is a life-threatening disorder caused by infection of individuals with the human immunodeficiency virus (HIV). Entry of HIV-1 into target cells depends on the presence of two surface proteins on the cell membrane: CD4, which serves as the main receptor, and either CCR5 or CXCR4 as a co-receptor. A limited number of people harbor a genomic 32-bp deletion in the CCR5 gene (CCR5∆32), leading to expression of a truncated gene product that provides resistance to HIV-1 infection in individuals homozygous for this mutation. Moreover, allogeneic hematopoietic stem cell (HSC) transplantation with CCR5∆32 donor cells seems to confer HIV-1 resistance to the recipient as well. However, since Δ32 donors are scarce and allogeneic HSC transplantation is not exempt from risks, the development of gene editing tools to knockout CCR5 in the genome of autologous cells is highly warranted. Targeted gene editing can be accomplished with designer nucleases, which essentially are engineered restriction enzymes that can be designed to cleave DNA at specific sites. During repair of these breaks, the cellular repair pathway often introduces small mutations at the break site, which makes it possible to disrupt the ability of the targeted locus to express a functional protein, in this case CCR5. Here, we review the current promise and limitations of CCR5 gene editing with engineered nucleases, including factors affecting the efficiency of gene disruption and potential off-target effects.

  9. Roles of CcrA and CcrB in Excision and Integration of Staphylococcal Cassette Chromosome mec, a Staphylococcus aureus Genomic Island▿

    OpenAIRE

    Wang, Lei; Archer, Gordon L.

    2010-01-01

    The gene encoding resistance to methicillin and other β-lactam antibiotics in staphylococci, mecA, is carried on a genomic island, SCCmec (for staphylococcal cassette chromosome mec). The chromosomal excision and integration of types I to IV SCCmec are catalyzed by the site-specific recombinases CcrA and CcrB, the genes for which are encoded on each element. We sought to identify the relative contributions of CcrA and CcrB in the excision and integration of SCCmec. Purified CcrB but not CcrA ...

  10. Inefficient entry of vicriviroc-resistant HIV-1 via the inhibitor-CCR5 complex at low cell surface CCR5 densities

    OpenAIRE

    Pugach, Pavel; Ray, Neelanjana; Klasse, Per Johan; Ketas, Thomas J.; Michael, Elizabeth; Doms, Robert W.; Lee, Benhur; Moore, John P.

    2009-01-01

    HIV-1 variants resistant to small molecule CCR5 inhibitors such as vicriviroc (VVC) have modified Env complexes that can use both the inhibitor-bound and -free forms of the CCR5 co-receptor to enter target cells. However, entry via the inhibitor-CCR5 complex is inefficient in some, but not all, cell types, particularly cell lines engineered to express CCR5. We investigated the effect of increasing CCR5 expression, and hence the density of the inhibitor-CCR5 complex when a saturating inhibitor...

  11. The CCR5 receptor acts as an alloantigen in CCR5Δ32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies

    OpenAIRE

    Ditzel, Henrik J.; Rosenkilde, Mette M.; Garred, Peter; Wang, Meng; Koefoed, Klaus; Pedersen, Court; Burton, Dennis R.; Schwartz, Thue W.

    1998-01-01

    The chemokine receptor CCR5 is the major coreceptor for infection by macrophage-tropic R5 HIV-1. A 32-bp deletion in the gene coding for CCR5 (CCR5Δ32) occurs with a frequency of 10% in the Caucasian population and results in a receptor protein that is truncated and not expressed at the cell surface. CCR5Δ32 homozygous individuals are apparently normal but resistant to infection with R5 HIV-1. In two individuals homozygous for CCR5Δ32, who had been repeatedly exposed to CCR5-expressing blood ...

  12. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  13. Clinical use of CCR5 inhibitors in HIV and beyond

    Directory of Open Access Journals (Sweden)

    Gilliam Bruce

    2010-01-01

    Full Text Available Abstract Since the discovery of CCR5 as a coreceptor for HIV entry, there has been interest in blockade of the receptor for treatment and prevention of HIV infection. Although several CCR5 antagonists have been evaluated in clinical trials, only maraviroc has been approved for clinical use in the treatment of HIV-infected patients. The efficacy, safety and resistance profile of CCR5 antagonists with a focus on maraviroc are reviewed here along with their usage in special and emerging clinical situations. Despite being approved for use since 2007, the optimal use of maraviroc has yet to be well-defined in HIV and potentially in other diseases. Maraviroc and other CCR5 antagonists have the potential for use in a variety of other clinical situations such as the prevention of HIV transmission, intensification of HIV treatment and prevention of rejection in organ transplantation. The use of CCR5 antagonists may be potentiated by other agents such as rapamycin which downregulate CCR5 receptors thus decreasing CCR5 density. There may even be a role for their use in combination with other entry inhibitors. However, clinical use of CCR5 antagonists may have negative consequences in diseases such as West Nile and Tick-borne encephalitis virus infections. In summary, CCR5 antagonists have great therapeutic potential in the treatment and prevention of HIV as well as future use in novel situations such as organ transplantation. Their optimal use either alone or in combination with other agents will be defined by further investigation.

  14. Metilação e CCR

    OpenAIRE

    Soares, Mónica Sofia Barroso

    2016-01-01

    Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz O Cancro Cólon Retal (CCR) é um dos cancros mais comuns no mundo, sendo o terceiro mais frequente e mortal a nível mundial, com uma incidência de cerca de 9% e provocando a morte de aproximadamente 394000 pessoas/ano. O desenvolvimento desta neoplasia surge maioritariamente associado a uma sequência e acumulação de mutações genéticas, designada sequência adenoma-carcinoma. Esta doença pode tam...

  15. Misinformation with fake news

    Directory of Open Access Journals (Sweden)

    M. BOTEI

    2017-12-01

    Full Text Available The last presidential elections in the United States of America (2016 have brought to the international public opinion’ s attention the phenomenon of “fake news”. Though it isn’t a new phenomenon, the spread of fake information for manipulating and misinforming the masses has existed in all historical periods. This time the phenomenon was noticed because of the number of fake news and, especially because of their impact, starting the discussion whether the victory of Donald Trump happened because of fake news and raising the question whether this phenomenon is a danger to democracy. An important reaction came also from the part of technology companies, of tech giants, Google and Facebook especially, which want the implementation of the phenomenon. Misinformation with public speech under the form of fake news brings to discussion the responsibility in the online space, but also the protection of people against this phenomenon.

  16. Is the Internet Bad News? The Online News Era and the Market for High-Quality News

    OpenAIRE

    Frijters, Paul; Velamuri, Malathi

    2009-01-01

    We review and model the impact of the internet on the production and uptake of high- quality news. Our review of trends in the market for news suggests 3 stylized facts: i) particular quality news markets are dominated by merely a few providers, ii) demand for quality news appears stable, but provision of news has become specialized; mainstream news is decoupled from quality news, and iii) the dominant business model of internet news mirrors that of radio, television, and newsp...

  17. Global news production

    DEFF Research Database (Denmark)

    Clausen, Lisbeth

    Events around the world are broadcast by giant media players such as CNN, BBC and NHK amongst others. Consumers of news media receive the final message without knowing the processes that the images, the text and the sound have gone through. The media players can be considered as professional...... generators of national news, who manipulate presentations according to professional standards as well as local needs that are culturally based. This book explores how powerful political and economic agendas in the national media environment influence the production processes. It shows how the outcome...

  18. Googling the news

    DEFF Research Database (Denmark)

    Ørmen, Jacob

    2016-01-01

    Search engines provide a window into the changing association between websites and keywords across cultures and countries and over time. As such, they offer journalism and news researchers an opportunity to study how search engines, in this case Google, mediate news events and stories online....... However, search results are not straightforward to study. Since search results are made in the act of searching and will have to be retrieved from Google Search in real-time, there is a range of different ontological and methodological issues related to this data source. This paper addresses these issues...

  19. Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Knudsen, T B; Kristiansen, T B; Katzenstein, T L

    2001-01-01

    HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5 encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell surface and a slower progression towards AIDS and death. Other human polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A....... Genotypes were determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When including the concurrent effects of the CCR5 Delta32 and CCR2 64I mutations, homozygous carriers of the CCR5 promoter -2459A allele had a significantly faster progression towards death than heterozygous A/G individuals...... (P = 0.03), whereas this adverse effect was not significant when comparing A/A and G/G individuals. However, independent analysis revealed a significant adverse effect of the CCR5 promoter -2459A allele. Homozygous carriers of the -2459A allele that lack the protective effects of the CCR5 Delta32...

  20. Genotyping of CCR5 gene, CCR2b and SDF1 variants related to HIV-1 infection in Gabonese subjects.

    Science.gov (United States)

    Mombo, Landry Erik; Bisseye, Cyrille; Mickala, Patrick; Ossari, Simon; Makuwa, Maria

    2015-01-01

    Given the magnitude of the HIV epidemic infection, many viral and human factors were analyzed, and the most decisive was the variant CCR5-Δ32. The presence of a low HIV prevalence (1.8%) in Gabon in the 1990s, compared to neighboring countries, represents a paradox that led us to search for viral and human genetic variants in this country. In this study, only variants of coreceptors and chemokines were investigated. Variants of the coding region of the CCR5 gene were analyzed by denaturing gradient gel electrophoresis, and then variants of SDF1 and CCR2b were determined by polymerase chain reaction-restriction fragment length polymorphism. Four rare variants of the CCR5 coreceptor were found, while CCR5-Δ32 and CCR5m303 variants were not found. No association with CCR2b-V64I (17%) and SDF1-3'A (2%) variants was determined in relation to HIV-1 infection in Gabonese patients. The paradox of HIV seroprevalence in Gabon, which ended in the 2000s, was not caused by human genetic variants but rather by environmental factors. © 2015 S. Karger AG, Basel.

  1. Cloning and expression analysis of cinnamoyl-CoA reductase (CCR) genes in sorghum.

    Science.gov (United States)

    Li, Jieqin; Fan, Feifei; Wang, Lihua; Zhan, Qiuwen; Wu, Peijin; Du, Junli; Yang, Xiaocui; Liu, Yanlong

    2016-01-01

    Cinnamoyl-CoA reductase (CCR) is the first enzyme in the monolignol-specific branch of the lignin biosynthetic pathway. In this research, three sorghum CCR genes including SbCCR1, SbCCR2-1 and SbCCR2-2 were cloned and characterized. Analyses of the structure and phylogeny of the three CCR genes showed evolutionary conservation of the functional domains and divergence of function. Transient expression assays in Nicotiana benthamiana leaves demonstrated that the three CCR proteins were localized in the cytoplasm. The expression analysis showed that the three CCR genes were induced by drought. But in 48 h, the expression levels of SbCCR1 and SbCCR2-2 did not differ between CK and the drought treatment; while the expression level of SbCCR2-1 in the drought treatment was higher than in CK. The expression of the SbCCR1 and SbCCR2-1 genes was not induced by sorghum aphid [Melanaphis sacchari (Zehntner)] attack, but SbCCR2-2 was significantly induced by sorghum aphid attack. It is suggested that SbCCR2-2 is involved in the process of pest defense. Absolute quantitative real-time PCR revealed that the three CCR genes were mainly expressed in lignin deposition organs. The gene copy number of SbCCR1 was significantly higher than those of SbCCR2-1 and SbCCR2-2 in the tested tissues, especially in stem. The results provide new insight into the functions of the three CCR genes in sorghum.

  2. Automatic Detection of Fake News

    OpenAIRE

    Pérez-Rosas, Verónica; Kleinberg, Bennett; Lefevre, Alexandra; Mihalcea, Rada

    2017-01-01

    The proliferation of misleading information in everyday access media outlets such as social media feeds, news blogs, and online newspapers have made it challenging to identify trustworthy news sources, thus increasing the need for computational tools able to provide insights into the reliability of online content. In this paper, we focus on the automatic identification of fake content in online news. Our contribution is twofold. First, we introduce two novel datasets for the task of fake news...

  3. Breaking Bad News to Parents.

    Science.gov (United States)

    Miller, Susan A.

    1996-01-01

    Discusses the difficulty of breaking bad news to parents, whether the news pertains to center policy or a child's behavior. Provides strategies for presenting news and for helping parents to overcome difficult situations, including gathering facts in advance, arranging an appropriate time, and having resource materials available for parents. (MOK)

  4. The Trouble with Bad News.

    Science.gov (United States)

    Haskins, Jack B.

    1981-01-01

    Subjective comments from veteran news reporters, media critics, and the public give the impression that bad or negative news is becoming a major problem in this country. This impression raises major questions concerning how much is really known about bad news, including whether the media present an accurate or distorted picture of reality in…

  5. Crime News Coverage in Perspective.

    Science.gov (United States)

    Graber, Doris A.

    According to one sociological model, news is a product of socially determined notions of who and what is important and the organizational structures that result for routinizing news collection; events that deviate from these notions are ignored. This report describes a study of crime news coverage in the media that used this model to examine the…

  6. Figuring Out Health News

    Science.gov (United States)

    ... was gathering information for a research project on teens and suicide. She came across a news article about how ... the study results didn't mean all the teens in the study committed suicide while on the medication. In fact, in this ...

  7. Parent News Offline, 2003.

    Science.gov (United States)

    Robertson, Anne S., Ed.

    2003-01-01

    This document is comprised of the two issues in volume 5 of "Parent News Offline," a publication of the National Parent Information Network (NPIN) designed to introduced those without Internet Access to the activities and information available through NPIN. The Spring 2003 issue contains the following articles: (1) "Summer Academic…

  8. Television News Without Pictures?

    Science.gov (United States)

    Graber, Doris A.

    1987-01-01

    Describes "gestalt" coding procedures that concentrate on the meanings conveyed by audio-visual messages rather than on coding individual pictorial elements shown in a news story. Discusses the totality of meaning that results from the interaction of verbal and visual story elements, external settings, and the decoding proclivities of…

  9. News from Afar

    DEFF Research Database (Denmark)

    Harmsen, Peter

    . This paper describes the way a number of Danish news outlets reported on three key battles in the Pacific: the attack on Pearl Harbor in December 1941, the battle of Midway in June 1942, and the battle of Iwo Jima in the spring of 1945, held against examples of the importance attributed to the Pacific...

  10. News and Trading Rules

    Science.gov (United States)

    2003-01-01

    of employee options. (“ TIBCO Software Announces Stock Option Exchange Program for Employees”, TIBX, 3/8/2001) • Product/Sales Activity: This category...NAND “reverse” 2. “split(s)?” AND “stock” NAND “reverse” • Options: News of a company’s treatment of employee options. (“ TIBCO Soft- ware Announces

  11. Good Friends, Bad News

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Arvidsson, Adam; Nielsen, Finn Årup

    the NY Times finds a strong link between positive affect and virality, and, based on psychological theories it is concluded that this relation is universally valid. The conclusion appears to be in contrast with classic theory of diffusion in news media emphasizing negative affect as promoting propagation...

  12. Multimodal news framing effects

    NARCIS (Netherlands)

    Powell, T.E.

    2017-01-01

    Visuals in news media play a vital role in framing citizens’ political preferences. Yet, compared to the written word, visual images are undervalued in political communication research. Using framing theory, this thesis redresses the balance by studying the combined, or multimodal, effects of visual

  13. Making news about medicines

    NARCIS (Netherlands)

    Trigt, Anna Maria van

    1995-01-01

    People are very interested in information about health and illness. Studies show that they are more interested in new medical discoveries than in sport in the news. Mass media channels (e.g. newspapers, television) do pay attention to information about health and illness. Both patients, health

  14. VULTURE NEWS 55.indd

    African Journals Online (AJOL)

    2006-06-18

    Jun 18, 2006 ... near San Lucas, but the marksmen didn't use non-lead ammunition. Condors eat only carrion – dead carcasses – and are highly susceptible to lead poisoning if they ingest lead bullet ... came in and started eating everything,”. Petersen said. News of the ... And yet the state refuses to act.” Earlier this.

  15. CERN television news

    CERN Multimedia

    2002-01-01

    CERN events brought right to your desktop by the new video bulletin.   CERN now has its very own news broadcast , or rather 'webcast', with a host of special reports and even a star presenter. From today onwards, just go to the Bulletin's web page, click on the 'video news' link and sit back and enjoy the latest news about CERN, presented in images by Wendy Korda. The ten-minute newscast in both French and English, the Organization's two official languages, presents interviews, pictures of experiments and computer-generated graphics, bringing you right up to date with some of the Laboratory's latest stories. The show concludes with a selection of the best snapshots taken by the CERN Photo Lab. So every one or two months CERN's Audio-Video Service (ETT/DH) will be putting together a video news report that you can watch on your own desktop computer. Daniel Boileau, Patrick Gilbert de Vautibault and Jacques Fichet, the Service's three technicians, came up with the idea of producing this regular feat...

  16. Global news production

    DEFF Research Database (Denmark)

    Clausen, Lisbeth

    Events around the world are broadcast by giant media players such as CNN, BBC and NHK amongst others. Consumers of news media receive the final message without knowing the processes that the images, the text and the sound have gone through. The media players can be considered as professional...

  17. The chemokine receptor CCR5 in the central nervous system.

    Science.gov (United States)

    Sorce, Silvia; Myburgh, Renier; Krause, Karl-Heinz

    2011-02-01

    The expression and the role of the chemokine receptor CCR5 have been mainly studied in the context of HIV infection. However, this protein is also expressed in the brain, where it can be crucial in determining the outcome in response to different insults. CCR5 expression can be deleterious or protective in controlling the progression of certain infections in the CNS, but it is also emerging that it could play a role in non-infectious diseases. In particular, it appears that, in addition to modulating immune responses, CCR5 can influence neuronal survival. Here, we summarize the present knowledge about the expression of CCR5 in the brain and highlight recent findings suggesting its possible involvement in neuroprotective mechanisms. Copyright © 2011. Published by Elsevier Ltd.

  18. Blended news delivery in healthcare: a framework for injecting good news into bad news conversations.

    Science.gov (United States)

    Legg, Angela M; Sweeny, Kate

    2015-01-01

    Clinicians often inject good news into bad news delivery, and they do so for a variety of reasons. We present a framework that draws from research in the fields of health and social psychology to shed light on situations in which clinicians add superfluous good news into bad news conversations in an effort to ease the conversation or mitigate patients' distress, a broad strategy we refer to as blended news delivery. Our framework includes predictors of clinicians' use of blended news delivery, characteristics of blended news and outcomes of this strategy for both patients and clinicians. This framework addresses a common aspect of health communication and can direct future research on ideal strategies for and likely consequences of blended news delivery and communication more broadly.

  19. BBC VERSUS EURO NEWS: DISCOURSE AND IDEOLOGY IN NEWS TRANSLATION

    Directory of Open Access Journals (Sweden)

    Hosseini, F.

    2016-09-01

    Full Text Available The present study aimed to compare discursive strategies employed by two international news agencies including Euro News and BBC. Van Dijk’s (2004 model of CDA was adopted. Thirty pieces of news about internal affairs of Iran together with their Persian translations were downloaded from the corresponding website, i.e. 30 pieces of English news and their corresponding Persian translations from the Euro News website and 30 pieces of English news with their corresponding translations from the BBC website. The frequency of lexical items was observed to not differ significantly. Two sets of translations were compared to their source texts based on four discursive strategies of hyperbole, polarization, vagueness and euphemism. An independent-samples t-test was conducted to compare the frequency of strategies applied by the two news agencies. Results revealed no significant difference between the two agencies except for the discursive strategy of vagueness.

  20. Relevance of CCL3/CCR5 axis in oral carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Moreira Dos Santos, Tálita Pollyanna; Sobral, Lays Martin; Queiroz-Junior, Celso Martins; Rachid, Milene Alvarenga; Proudfoot, Amanda E I; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; Teixeira, Mauro Martins; Leopoldino, Andréia Machado; Russo, Remo Castro; Silva, Tarcília Aparecida

    2017-08-01

    The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro . The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3 -/- and CCR5 -/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1 -/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3 -/- and CCR5 -/- mice. OSCC from CCL3 -/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro , CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.

  1. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen atCCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  2. The case for selection at CCR5-Delta32.

    Directory of Open Access Journals (Sweden)

    Pardis C Sabeti

    2005-11-01

    Full Text Available The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32 allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14% in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5, they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

  3. Delivering bad news to patients

    Science.gov (United States)

    Gentry, Lonnie; Cox, Thomas R.

    2016-01-01

    When physicians lack proper training, breaking bad news can lead to negative consequences for patients, families, and physicians. A questionnaire was used to determine whether a didactic program on delivering bad news was needed at our institution. Results revealed that 91% of respondents perceived delivering bad news as a very important skill, but only 40% felt they had the training to effectively deliver such news. We provide a brief review of different approaches to delivering bad news and advocate for training physicians in a comprehensive, structured model. PMID:26722188

  4. Short Communication: HIV-1 Variants That Use Mouse CCR5 Reveal Critical Interactions of gp120's V3 Crown with CCR5 Extracellular Loop 1.

    Science.gov (United States)

    Platt, Emily J; Durnin, James P; Kabat, David

    2015-10-01

    The CCR5 coreceptor amino terminus and extracellular (ECL) loops 1 and 2 have been implicated in HIV-1 infections, with species differences in these regions inhibiting zoonoses. Interactions of gp120 with CD4 and CCR5 reduce constraints on metastable envelope subunit gp41, enabling gp41 conformational changes needed for infection. We previously selected HIV-1JRCSF variants that efficiently use CCR5(Δ18) with a deleted amino terminus or CCR5(HHMH) with ECL2 from an NIH/Swiss mouse. Unexpectedly, the adaptive gp120 mutations were nearly identical, suggesting that they function by weakening gp120's grip on gp41 and/or by increasing interactions with ECL1. To analyze this and further wean HIV-1 from human CCR5, we selected variants using CCR5(HMMH) with murine ECL1 and 2 sequences. HIV-1JRCSF mutations adaptive for CCR5(Δ18) and CCR5(HHMH) were generally maladaptive for CCR5(HMMH), whereas the converse was true for CCR5(HMMH) adaptations. The HIV-1JRCSF variant adapted to CCR5(HMMH) also weakly used intact NIH/Swiss mouse CCR5. Our results strongly suggest that HIV-1JRCSF makes functionally critical contacts with human ECL1 and that adaptation to murine ECL1 requires multiple mutations in the crown of gp120's V3 loop.

  5. Vulture News: Site Map

    African Journals Online (AJOL)

    Journal Home · Journals · Vulture News · About · Log In · Register · Advanced Search · By Author · By Title. Issues. Current Issue · Archives · Open Journal Systems · Help. ISSN: 1606-7479. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's ...

  6. NetWorking News

    DEFF Research Database (Denmark)

    Fritsch, Jonas; Iversen, Ole Sejer; Dindler, Christian

    with adults or children. However there is a need for new methods to support communication and collaboration between designers and children. This article proposes a new method for understandings children’s appropriation of new technology in an interactive workshop setting. The method, which we call...... the Networking News workshop, offers an opportunity to make first hand studies of children’s IT supported social activities in an informal classroom setting....

  7. NetWorking News

    DEFF Research Database (Denmark)

    Fritsch, Jonas; Iversen, Ole Sejer; Dindler, Christian

    For many years cooperative design was primarily concerned with the development of IT supported systems for professional users. However, the cooperative design approach can embrace other social practices such as children’s everyday life. At a methodological level there is no difference in designin...... the Networking News workshop, offers an opportunity to make first hand studies of children’s IT supported social activities in an informal classroom setting....

  8. Haberin Geleceği: Gazetelerle İlgili Bilgi Hizmetlerinin Yapılanması ve Kullanımı / The Future of News: Building and Using Information Services in Connection with Newspapers

    Directory of Open Access Journals (Sweden)

    H. İnci Önal

    2007-04-01

    Full Text Available The purpose of the present research is to specify the current stand and future of information services in providing news. Libraries and archives that collect newspapers, and supply services to let the readers to have quick and easy access to their contents, increase their activities and in conjunction to this, their experience. As an initial step of the present research, by methods of interviewing and administering questionnaires, Ankara branch office responsible of six nationwide distributed daily newspapers were investigated. Data were compiled about the present situation, provided services, problems to be confronted, and work plans. According to the evaluations, it seems that the developments in information technologies would also impose important tasks to librariesin case of disseminating newspaper information.

  9. Contact: Releasing the news

    Science.gov (United States)

    Pinotti, Roberto

    The problem of mass behavior after man's future contacts with other intelligences in the universe is not only a challenge for social scientists and political leaders all over the world, but also a cultural time bomb as well. In fact, since the impact of CETI (Contact with Extraterrestrial Intelligence) on human civilization, with its different cultures, might cause a serious socio-anthropological shock, a common and predetermined worldwide strategy is necessary in releasing the news after the contact, in order to keep possible manifestations of fear, panic and hysteria under control. An analysis of past studies in this field and of parallel historical situations as analogs suggests a definite "authority crisis" in the public as a direct consequence of an unexpected release of the news, involving a devastating "chain reaction" process (from both the psychological and sociological viewpoints) of anomie and maybe the collapse of today's society. The only way to prevent all this is to prepare the world's public opinion concerning contact before releasing the news, and to develop a long-term strategy through the combined efforts of scientists, political leaders, intelligence agencies and the mass media, in order to create the cultural conditions in which a confrontation with ETI won't affect mankind in a traumatic way. Definite roles and tasks in this multi-level model are suggested.

  10. 20 CFR 404.1030 - Delivery and distribution or sale of newspapers, shopping news, and magazines.

    Science.gov (United States)

    2010-04-01

    ... newspapers, shopping news, and magazines. 404.1030 Section 404.1030 Employees' Benefits SOCIAL SECURITY... of newspapers, shopping news, and magazines. (a) If you are under age 18. Work you do before you... are, work you do in connection with and at the time of the sale of newspapers or magazines to...

  11. Epitope Switching as a Novel Escape Mechanism of HIV to CCR5 Monoclonal Antibodies▿

    OpenAIRE

    Jekle, Andreas; Chhabra, Milloni; Lochner, Adriane; Meier, Sonja; Chow, Eugene; Brandt, Michael; Sankuratri, Surya; Cammack, Nick; Heilek, Gabrielle

    2009-01-01

    In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that...

  12. News media old and new

    DEFF Research Database (Denmark)

    Schrøder, Kim Christian

    2014-01-01

    This article presents and discusses three different approaches to the exploration of the cross-media challenges facing news audiences, as they seek access to, navigate in and make sense of the multitude of news sources across print, broadcasting, online and mobile media platforms. From a modernized...... uses and gratifications perspective, based on the notion of “worthwhileness” as the determinant of people's everyday selections from the “supermarket of news”, the article first reports from a longitudinal survey study in Denmark in which the author's foundational mapping of cross-media news...... consumption in pre-mobile 2008 is compared with replicating mappings carried out in 2011 and 2012, in a collaborative project between academics and news publishers. The analytical interest here focuses on the fluctuations between traditional news media and the surging digital news outlets of the internet...

  13. Depletion of Gut-Resident CCR5+Cells for HIV Cure Strategies.

    Science.gov (United States)

    Merriam, David; Chen, Connie; Méndez-Lagares, Gema; Rogers, Kenneth A; Michaels, Anthony J; Yan, Jiangli; Casaz, Paul; Reimann, Keith A; Villinger, François; Hartigan-O'Connor, Dennis J

    2017-11-01

    The HIV reservoir forming at the earliest stages of infection is likely composed of CCR5 + cells, because these cells are the targets of transmissible virus. Restriction of the CCR5 + reservoir, particularly in the gut, may be needed for subsequent cure attempts. Strategies for killing or depleting CCR5 + cells have been described, but none have been tested in vivo in nonhuman primates, and the extent of achievable depletion from tissues is not known. In this study we investigate the efficacy of two novel cytotoxic treatments for targeting and eliminating CCR5 + cells in young rhesus macaques. The first, an immunotoxin consisting of the endogenous CCR5 ligand RANTES fused with Pseudomonas exotoxin (RANTES-PE38), killed CCR5 + lamina propria lymphocytes (LPLs) ex vivo, but had no detectable effect on CCR5 + LPLs in vivo. The second, a primatized bispecific antibody for CCR5 and CD3, depleted all CCR5 + cells from blood and the vast majority of such cells from the colonic mucosa (up to 96% of CD4 + CCR5 + ). Absence of CCR5-expressing cells from blood endured for at least 1 week, while CCR5 + cells in colon were substantially replenished over the same time span. These data open an avenue to investigation of combined early ART treatment and CCR5 + reservoir depletion for cure of HIV-infected infants.

  14. The Effects of Bad News and Good News on a Newspaper's Image.

    Science.gov (United States)

    Haskins, Jack B.; Miller, M. Mark

    1984-01-01

    Concludes that whether a newspaper carries mostly good news or mostly bad news affects the image of the paper, with bad news having negative effects and good news having positive effects on readers' perceptions of the newspaper. (FL)

  15. CCR5 Expression Levels Influence NFAT Translocation, IL-2 Production, and Subsequent Signaling Events during T Lymphocyte Activation1

    OpenAIRE

    Camargo, Jose F.; Quinones, Marlon P.; Mummidi, Srinivas; Srinivas, Sowmya; Gaitan, Alvaro A.; Begum, Kazi; Jimenez, Fabio; VanCompernolle, Scott; Unutmaz, Derya; Ahuja, Seema S.; Ahuja, Sunil K.

    2009-01-01

    Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5+/+, T cells from CCR5−/− mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-Δ32/Δ32 homozygotes) as well as after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5 expression. Conversely, overexpression of C...

  16. Epitope Switching as a Novel Escape Mechanism of HIV to CCR5 Monoclonal Antibodies▿

    Science.gov (United States)

    Jekle, Andreas; Chhabra, Milloni; Lochner, Adriane; Meier, Sonja; Chow, Eugene; Brandt, Michael; Sankuratri, Surya; Cammack, Nick; Heilek, Gabrielle

    2010-01-01

    In passaging experiments, we isolated HIV strains resistant to MAb3952, a chemokine (C-C motif) receptor 5 (CCR5) monoclonal antibody (MAb) that binds to the second extracellular domain (extracellular loop 2 [ECL-2]) of CCR5. MAb3952-resistant viruses remain CCR5-tropic and are cross-resistant to a second ECL-2-specific antibody. Surprisingly, MAb3952-resistant viruses were more susceptible to RoAb13, a CCR5 antibody binding to the N terminus of CCR5. Using CCR5 receptor mutants, we show that MAb3952-resistant virus strains preferentially use the N terminus of CCR5, while the wild-type viruses preferentially use ECL-2. We propose this switch in the CCR5 binding site as a novel mechanism of HIV resistance. PMID:19995923

  17. CCR Certification Form for Wyoming or EPA R8 Tribal Community Water Systems

    Science.gov (United States)

    The CCR Certification Form can be used to certify that community water systems in Wyoming or on Tribal Lands in EPA Region 8 have completed and distributed their annual Consumer Confidence Report (CCR) or water quality report.

  18. In-silico guided discovery of novel CCR9 antagonists

    Science.gov (United States)

    Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

    2018-03-01

    Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

  19. The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

    DEFF Research Database (Denmark)

    Cédile, Oriane; Østerby Jørgensen, Line; Frank, Ida

    2017-01-01

    Thymic dendritic cells (DC) play a role in central tolerance. Three thymic DC subtypes have been described: plasmacytoid DC (pDC) and two conventional DC (cDC), CD8α+ Sirpα- DC and Sirpα+ CD8α- cDC. Both pDC and Sirpα+ cDC can take up antigen in periphery and migrate into the thymus in response t...... by CCL2 or CCR2 deficiency. Although some thymic progenitors expressed CCR2, this did not include those that give rise to pDC. Based on these results, we propose that CCR2 is involved in pDC homeostasis but its ligand CCL2 does not play a major role....

  20. News: Synthetic biology leading to specialty chemicals ...

    Science.gov (United States)

    Synthetic biology can combine the disciplines of biology, engineering, and chemistry productively to form molecules of great scientific and commercial value. Recent advances in the new field are explored for their connection to new tools that have been used to elucidate production pathways to a wide variety of chemicals generated by microorganisms. The selection and enhancement of microbiological strains through the practice of strain engineering enables targets of design, construction, and optimization. This news column aspires to cover recent literature relating to the development and understanding of clean technology.

  1. News from the world

    International Nuclear Information System (INIS)

    Anon.

    2006-01-01

    News from the world in relation with nuclear power and fuel cycle are given: Dismantling of the research reactor of the Pasteur Institute, Areva gets the contract to replace the vessel caps for the nuclear power plant of Diablo Canyon, the United Kingdom chooses the renewal of the nuclear park and an increase in the use of renewable energy sources, The united states launches a call to projects for the building of new generation nuclear power plants, in Argentina the government develops its nuclear industry, the Russian federation proposes the creation of an international center for the fuel cycle are the principal points that are developed in this issue. (N.C.)

  2. CERN Video News

    CERN Multimedia

    2003-01-01

    From Monday you can see on the web the new edition of CERN's Video News. Thanks to a collaboration between the audiovisual teams at CERN and Fermilab, you can see a report made by the American laboratory. The clip concerns the LHC magnets that are being constructed at Fermilab. Also in the programme: the spectacular rotation of one of the ATLAS coils, the arrival at CERN of the first American magnet made at Brookhaven, the story of the discovery 20 years ago of the W and Z bosons at CERN. http://www.cern.ch/video or Bulletin web page.

  3. News from the future

    DEFF Research Database (Denmark)

    Reinecke Hansen, Kenneth

    2016-01-01

    This article presents a corpus linguistic analysis of the development in future-oriented political journalism in four Danish newspapers in the period 1997–2013 (N = 2954 full articles = 1,553,038 word tokens). Keyword analysis and concordance analysis are applied within a framework of grammatical......-semantic theory of tense and modal verbs and semantic-pragmatic theory of time meaning, modality and speech acts. The results suggest, unexpectedly, that the newspapers – and news reports in particular – seem to have become less future-oriented in the period. At the same time, however, the articles...

  4. Nuclear waste: good news

    International Nuclear Information System (INIS)

    Gay, Michel

    2014-01-01

    The author states that the problem of nuclear wastes is solved. He states that 90 per cent of radioactive wastes are now permanently managed and that technical solutions for deep geological storage and for transmutation will soon solve the problem for the remaining 10 pc. He states that geological storage will be funded (it is included in electricity price). He denounces why these facts which he consider as good news, do not prevail. He proposes several documents in appendix: a text explaining the nuclear fuel cycle in France, and an extract of a report made by the national inventory of radioactive materials and wastes

  5. HIV-1 exploits CCR5 conformational heterogeneity to escape inhibition by chemokines.

    Science.gov (United States)

    Colin, Philippe; Bénureau, Yann; Staropoli, Isabelle; Wang, Yongjin; Gonzalez, Nuria; Alcami, Jose; Hartley, Oliver; Brelot, Anne; Arenzana-Seisdedos, Fernando; Lagane, Bernard

    2013-06-04

    CC chemokine receptor 5 (CCR5) is a receptor for chemokines and the coreceptor for R5 HIV-1 entry into CD4(+) T lymphocytes. Chemokines exert anti-HIV-1 activity in vitro, both by displacing the viral envelope glycoprotein gp120 from binding to CCR5 and by promoting CCR5 endocytosis, suggesting that they play a protective role in HIV infection. However, we showed here that different CCR5 conformations at the cell surface are differentially engaged by chemokines and gp120, making chemokines weaker inhibitors of HIV infection than would be expected from their binding affinity constants for CCR5. These distinct CCR5 conformations rely on CCR5 coupling to nucleotide-free G proteins ((NF)G proteins). Whereas native CCR5 chemokines bind with subnanomolar affinity to (NF)G protein-coupled CCR5, gp120/HIV-1 does not discriminate between (NF)G protein-coupled and uncoupled CCR5. Interestingly, the antiviral activity of chemokines is G protein independent, suggesting that "low-chemokine affinity" (NF)G protein-uncoupled conformations of CCR5 represent a portal for viral entry. Furthermore, chemokines are weak inducers of CCR5 endocytosis, as is revealed by EC50 values for chemokine-mediated endocytosis reflecting their low-affinity constant value for (NF)G protein-uncoupled CCR5. Abolishing CCR5 interaction with (NF)G proteins eliminates high-affinity binding of CCR5 chemokines but preserves receptor endocytosis, indicating that chemokines preferentially endocytose low-affinity receptors. Finally, we evidenced that chemokine analogs achieve highly potent HIV-1 inhibition due to high-affinity interactions with internalizing and/or gp120-binding receptors. These data are consistent with HIV-1 evading chemokine inhibition by exploiting CCR5 conformational heterogeneity, shed light into the inhibitory mechanisms of anti-HIV-1 chemokine analogs, and provide insights for the development of unique anti-HIV molecules.

  6. Use of G-Protein-Coupled and -Uncoupled CCR5 Receptors by CCR5 Inhibitor-Resistant and -Sensitive Human Immunodeficiency Virus Type 1 Variants

    Science.gov (United States)

    Berro, Reem; Yasmeen, Anila; Abrol, Ravinder; Trzaskowski, Bartosz; Abi-Habib, Sarya; Grunbeck, Amy; Lascano, Danny; Goddard, William A.; Klasse, Per Johan; Sakmar, Thomas P.

    2013-01-01

    Small-molecule CCR5 inhibitors such as vicriviroc (VVC) and maraviroc (MVC) are allosteric modulators that impair HIV-1 entry by stabilizing a CCR5 conformation that the virus recognizes inefficiently. Viruses resistant to these compounds are able to bind the inhibitor-CCR5 complex while also interacting with the free coreceptor. CCR5 also interacts intracellularly with G proteins, as part of its signal transduction functions, and this process alters its conformation. Here we investigated whether the action of VVC against inhibitor-sensitive and -resistant viruses is affected by whether or not CCR5 is coupled to G proteins such as Gαi. Treating CD4+ T cells with pertussis toxin to uncouple the Gαi subunit from CCR5 increased the potency of VVC against the sensitive viruses and revealed that VVC-resistant viruses use the inhibitor-bound form of Gαi-coupled CCR5 more efficiently than they use uncoupled CCR5. Supportive evidence was obtained by expressing a signaling-deficient CCR5 mutant with an impaired ability to bind to G proteins, as well as two constitutively active mutants that activate G proteins in the absence of external stimuli. The implication of these various studies is that the association of intracellular domains of CCR5 with the signaling machinery affects the conformation of the external and transmembrane domains and how they interact with small-molecule inhibitors of HIV-1 entry. PMID:23468486

  7. Enriquecimento com calda do CCR para face de barragens

    OpenAIRE

    Wendler,A. P.; Marques Filho,J.; Franco Filho,J. M. M.; Bianchini,M.

    2014-01-01

    A construção de barragens de CCR prioriza a minimização de interferências, como a execução da face de montante, para garantia da produtividade. O estudo procurou avaliar as propriedades físicas do CCR enriquecido com calda, em substituição ao concreto convencional usualmente empregado na face, utilizando os mesmos materiais, central de concreto, mão de obra e equipamentos, empregados na construção da Usina Hidrelétrica Mauá. Para tanto foram feitos prismas experimentais de campo (com diferent...

  8. Solution Structure of LC4 Transmembrane Segment of CCR5

    OpenAIRE

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescdence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 ...

  9. Molecular characterization and expression analysis of four fish-specific CC chemokine receptors CCR4La, CCR4Lc1, CCR4Lc2 and CCR11 in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Qi, Zhitao; Holland, Jason W; Jiang, Yousheng; Secombes, Christopher J; Nie, Pin; Wang, Tiehui

    2017-09-01

    The chemokine and chemokine receptor networks regulate leukocyte trafficking, inflammation, immune cell differentiation, cancer and other biological processes. Comparative immunological studies have revealed that both chemokines and their receptors have expanded greatly in a species/lineage specific way. Of the 10 human CC chemokine receptors (CCR1-10) that bind CC chemokines, orthologues only to CCR6, 7, 9 and 10 are present in teleost fish. In this study, four fish-specific CCRs, termed as CCR4La, CCR4Lc1, CCR4Lc2 and CCR11, with a close link to human CCR1-5 and 8, in terms of amino acid homology and syntenic conservation, have been identified and characterized in rainbow trout (Oncorhynchus mykiss). These CCRs were found to possess the conserved features of the G protein-linked receptor family, including an extracellular N-terminal, seven TM domains, three extracellular loops and three intracellular loops, and a cytoplasmic carboxyl tail with multiple potential serine/threonine phosphorylation sites. Four cysteine residues known to be involved in forming two disulfide bonds are present in the extracellular domains and a DRY motif is present in the second intracellular loop. Signaling mediated by these receptors might be regulated by N-glycosylation, tyrosine sulfation, S-palmitoylation, a PDZ ligand motif and di-leucine motifs. Studies of intron/exon structure revealed distinct fish-specific CCR gene organization in different fish species/lineages that might contribute to the diversification of the chemokine ligand-receptor networks in different fish lineages. Fish-specific trout CCRs are highly expressed in immune tissues/organs, such as thymus, spleen, head kidney and gills. Their expression can be induced by the pro-inflammatory cytokines, IL-1β, IL-6 and IFNγ, by the pathogen associated molecular patterns, PolyIC and peptidoglycan, and by bacterial infection. These data suggest that fish-specific CCRs are likely to have an important role in immune

  10. Arctic Warming as News - Perils and Possibilities

    Science.gov (United States)

    Revkin, A. C.

    2015-12-01

    A science journalist in his 30th year covering human-driven climate change, including on three Arctic reporting trips, reflects on successes and setbacks as news media, environmentalists and Arctic communities have tried to convey the significance of polar change to a public for which the ends of the Earth will always largely be a place of the imagination.Novel challenges are arising in the 24/7 online media environment, as when a paper by a veteran climate scientist proposing a mechanism for abrupt sea-level rise became a big news story before it was accepted by the open-review journal to which it had been submitted. New science is digging in on possible connections between changing Arctic sea ice and snow conditions and disruptive winter weather in more temperate northern latitudes, offering a potential link between this distant region and the lives of ordinary citizens. As cutting-edge research, such work gets substantial media attention. But, as with all new areas of inquiry, uncertainty dominates - creating the potential for distracting the public and policymakers from the many aspects of anthropogenic climate change that are firmly established - but, in a way, boring because of that.With the challenges, there are unprecedented opportunities for conveying Arctic science. In some cases, researchers on expeditions are partnering with media, offering both scientists and news outlets fresh ways to convey the story of Arctic change in an era of resource constraints.Innovative uses of crittercams, webcams, and satellite observations offer educators and interested citizens a way to track and appreciate Arctic change. But more can be done to engage the public directly without the news media as an intermediary, particularly if polar scientists or their institutions test some of the established practices honed by more experienced communicators at NASA.

  11. Neuropathic pain inhibitor, RAP-103, is a potent inhibitor of microglial CCL1/CCR8.

    Science.gov (United States)

    Noda, Mami; Tomonaga, Daichi; Kitazono, Kota; Yoshioka, Yusaku; Liu, Jiadai; Rousseau, Jean-Philippe; Kinkead, Richard; Ruff, Michael R; Pert, Candace B

    2017-12-14

    Chemokine signaling is important in neuropathic pain, with microglial cells expressing chemokine (C-C motif) receptor CCR2, CCR5 and CCR8, all playing key roles. In the previous report (Padi et al., 2012), oral administration of a short peptide, RAP-103, for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rodents. As for the mechanism of the inhibiting effect of RAP-103, it was speculated to be due to dual blockade of CCR2 and CCR5. We report here that RAP-103 exhibits stronger antagonism for CCR8 (half maximal inhibitory concentration [IC 50 ] 7.7 fM) compared to CCR5 (IC 50  < 100 pM) in chemotaxis using primary cultured mouse microglia. In addition, RAP-103 at a concentration of 0.1 pM completely inhibits membrane ruffling and phagocytosis induced by chemokine (C-C motif) ligand 1 (CCL1), an agonist for CCR8. It has been shown that CCL1/CCR8 signaling is important in tactile allodynia induced by nerve ligation. Therefore, CCR8, among other chemokine receptors such as CCR2/CCR5, could be the most potent target for RAP-103. Inhibitory effects of RAP-103 on plural chemokine receptors may play important roles for broad clinical use in neuropathic pain treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. 77 FR 5471 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review

    Science.gov (United States)

    2012-02-03

    ... Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review AGENCY... stakeholder input on the Consumer Confidence Report (CCR) Rule as part of the agency's Retrospective Review of... implementing CCR delivery certification, use of CCRs to meet Tier 3 Public Notification requirements, and how...

  13. 77 FR 55833 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-11

    ... on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on Potential Approaches to Electronic Delivery of the CCR AGENCY: Environmental Protection Agency (EPA). ACTION... potential approaches for providing Consumer Confidence Reports (CCR) via electronic delivery. EPA plans to...

  14. Molecular requirements for inhibition of the chemokine receptor CCR8--probe-dependent allosteric interactions

    DEFF Research Database (Denmark)

    Rummel, Pia Cwarzko; Arfelt, K N; Baumann, L

    2012-01-01

    Here we present a novel series of CCR8 antagonists based on a naphthalene-sulfonamide structure. This structure differs from the predominant pharmacophore for most small-molecule CC-chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative...

  15. CERN Video News on line

    CERN Multimedia

    2003-01-01

    The latest CERN video news is on line. In this issue : an interview with the Director General and reports on the new home for the DELPHI barrel and the CERN firemen's spectacular training programme. There's also a vintage video news clip from 1954. See: www.cern.ch/video or Bulletin web page

  16. news interview talk: Organisational properties

    African Journals Online (AJOL)

    informational and debate news interviews in the political sphere manifested themselves in the. South African data. ... the fact that Clayman's (1991) analysis focuses solely on a corpus of political-news interview talk. Given that an ..... through the dry seasons, a gene from an arctic fish could protect tomatoes from frost.

  17. School Violence and the News

    Science.gov (United States)

    ... and teens have many sources of information about school shootings or other tragic events. They might see or hear news stories or graphic images on TV, radio, or online, over and over. ... of a news story about school violence can make some kids feel that might ...

  18. What Turns Events into News?

    Science.gov (United States)

    Tukachinsky, Riva

    2013-01-01

    "The New York Times" is known for its slogan ''All the News That's Fit to Print.'' But how do gatekeepers decide which events meet this criterion? Although some individuals might believe that the news constitutes an undistorted reflection of the social reality, students in communication courses have the…

  19. Science News of the Year.

    Science.gov (United States)

    Science News, 1981

    1981-01-01

    Reviews important science news stories of 1981 as reported in "Science News." Gives a one-sentence summary and volume and page references for each story. Groups items by topic including space and astronomy, archaeology and anthropology, technology, behavior, science and society, energy, environment, and specific science disciplines. (DC)

  20. Getting Out the Good News.

    Science.gov (United States)

    Paciancia, David

    1995-01-01

    A majority of American schools are meeting the challenge of educating children. A New York State district gets out the good news by producing school newsletters and videos, by constant and close contact with the local news media, and by forming ties with local real estate agents. (MLF)

  1. Cultural Knowledge in News Comprehension

    DEFF Research Database (Denmark)

    Mathieu, David

    2009-01-01

    This paper presents the main lines of the design and the findings of a reception study on news comprehension. This empirical study is a comparison of the comprehension processes of Danes and French Canadians over a set of news texts from both countries. Comprehension is explored from a cultural...

  2. A CENTURY OF NEWS DISCOURSE

    Directory of Open Access Journals (Sweden)

    Allan Bell

    2003-05-01

    Full Text Available This paper traces the development of news discourse across the 20th century ihrough a case study ofthe coverage of three expeditions to the South Pole: Captain Scott in 1912, Sir Edmund Hillary in 1958, and Peter Hillary in 1999. The way the news about the three expeditions reached New Zealand media serves as a framework and an illustration to examine three related issues: how technology has changed the time and place dimensions of news delivery; the consequent and concomitant shifts in news presentation; and associated changes in how humans have understood time and place. News values remain the same at a broad level across the century, but different in detail. Nationalism is obtrusive, but its focus shifts. In news practice, the deadline and the scoop drive the news in al1 three periods, but the scooping medium shifts from press to radio to television. The lapse between an event and its reporting shrinks exponentially from months to hours to minutes. The design of newspaper front pages changes radically, and news language compresses. There are social impacts, with newsworthy figures receiving closer exposure and the audience being cast in a more voyeuristic role.

  3. Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization.

    Science.gov (United States)

    Tejchman, Anna; Lamerant-Fayel, Nathalie; Jacquinet, Jean-Claude; Bielawska-Pohl, Aleksandra; Mleczko-Sanecka, Katarzyna; Grillon, Catherine; Chouaib, Salem; Ugorski, Maciej; Kieda, Claudine

    2017-05-09

    Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL21/CCR7 chemokine/receptor axis in a hypoxia-dependent manner. In the present model, breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3 cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor environment. In addition to its known effect on migration, CCL21/CCR7 interaction was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression undergoes a reduction of adhesion, making it an anti-adhesion molecule in the absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231 cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia-dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which influence PDPN expression.

  4. Assessing News Contagion in Finance

    Directory of Open Access Journals (Sweden)

    Paola Cerchiello

    2018-02-01

    Full Text Available The analysis of news in the financial context has gained a prominent interest in the last years. This is because of the possible predictive power of such content especially in terms of associated sentiment/mood. In this paper, we focus on a specific aspect of financial news analysis: how the covered topics modify according to space and time dimensions. To this purpose, we employ a modified version of topic model LDA, the so-called Structural Topic Model (STM, that takes into account covariates as well. Our aim is to study the possible evolution of topics extracted from two well known news archive—Reuters and Bloomberg—and to investigate a causal effect in the diffusion of the news by means of a Granger causality test. Our results show that both the temporal dynamics and the spatial differentiation matter in the news contagion.

  5. Climate News Across Media Platforms

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2015-01-01

    In a changing media landscape marked by technological, institutional and cultural convergence, comparative and cross-media content analysis represents a valuable analytical tool in mapping the diverse channels of climate change communication. This paper presents a comparative study of climate...... change news on five different media platforms: newspapers, television, radio, web-news and mobile news. It investigates the themes and actors represented in public climate change communication as well as the diverse possibilities of participating in public debates and information sharing. By combining...... quantitative and qualitative content analysis the paper documents and explores the extent and character of climate change news across different media platforms. The study aims at contributing to the on-going assessment of how news media are addressing climate change at a time when old and new media...

  6. Gene polymorphisms in CCR5, CCR2, SDF1 and RANTES among Chinese Han population with HIV-1 infection.

    Science.gov (United States)

    Li, Hui; Liu, Ting-Jun; Hong, Ze-Hui

    2014-06-01

    Chemokines and chemokine receptors are crucial for immune response in HIV-1 infection. Although many studies have been done to investigate the relationship between chemokines and chemokine receptor gene polymorphisms and host's susceptibility to HIV-1 infection, the conclusions are under debate. In the present study, a cohort of 287 HIV-1 seropositive patients, 388 ethnically age-matched healthy controls and 49 intravenous drug users (IDUs) HIV-1 exposed seronegative individuals (HESN) from Chinese Han population were enrolled in order to determine the influence of host genetic factors on HIV-1 infection. Seven polymorphisms on four known chemokines/chemokine receptor genes (CCR5Δ32, CCR5 m303, CCR5 59029A/G, CCR2 64I, RANTES -403A/G, RANTES -28C/G and SDF1 3'-A) were screened. CCR5Δ32 and CCR5 m303 were absent or infrequent in Chinese Han population, which may not be hosts' genetic protective factors for HIV-1 infection. Our results showed the CCR5 59029A/G, CCR2 64I and SDF1 3'-A were not associated with host's resistance to HIV-1 infection. The frequency of RANTES -403A allele was significantly lower in HIV-1 patients than in healthy blood donors (p=0.0005) and HESN group (p=0.035), which implied the association between A allele and reduced HIV-1 infection risk. Different genetic models were assessed to investigate this association (AA vs. GG+AG, OR=0.38 95% CI, 0.22-0.65 p=0.0004; A vs. G, OR=0.66 95% CI, 0.52-0.84 p=0.0006), which supported this association, either. The genotype and allele distribution of RANTES -28 between HIV-1 patients and healthy controls (genotype profile: p=0.072; allele profile: p=0.027) or HIV-1 seronegative group (genotype profile: p=0.036; allele profile: p=0.383) were both at the marginal level of significance, which were not observed after Bonferroni correction. All these results suggest the RANTES -403A may be associated with reduced susceptibility to HIV-1 infection, while the RANTES -28 locus not. By lack of the patients

  7. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression

    DEFF Research Database (Denmark)

    Ioannidis, J P; Rosenberg, P S; Goedert, J J

    2001-01-01

    seroconversion. Data were combined with fixed-effects and random-effects models. RESULTS: Both the CCR5-Delta32 and CCR2-64I alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively; P = 0.01 for both), a decreased risk for death...... (relative hazard among seroconverters, 0.64 and 0.74; P CCR5-Delta32 or CCR2-64I allele had no clear protective effect on the risk for death.......00), or death after development of AIDS (relative hazard, 0.81 and 0.97; P > 0.5 for all). CONCLUSIONS: The CCR5-Delta32 and CCR2-64I alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 3'A homozygosity carried no such protection....

  8. Approach for Developing Scientific News Aggregators Using ATOM Feeds

    OpenAIRE

    Farha Shaikh; Anand Rajawa

    2012-01-01

    Scientists want to stay connected with everything that is new and innovative in the world, so they constantly read and analyze several online scientific resources such as magazines and journals. A user needs to do a lot of searching through on the web to locate the articles which are important to their interest. The idea of a news aggregator is not new to scientific world. A news aggregator is a software application, which periodically reads several sources and displays them on a separate pag...

  9. Investigating people’s news diets: how online news users use offline news

    NARCIS (Netherlands)

    Trilling, D.; Schoenbach, K.

    2015-01-01

    The question how offline media use is related to online media use has been heavily debated in the last decades. If they are functionally equivalent, then advantages like low costs, rapid publication cycles, and easy access to online news could lead to them displacing offline news. Data from a

  10. Central extensions for the Weyl CCR in Curved space

    International Nuclear Information System (INIS)

    Emch, G.G.

    1993-01-01

    For non-necessarily flat homogeneous configuration spaces, we illustrate how the cohomological choices made in the definition a Weyl group of the CCR are reflected in the momentum map for the action of this group on its co-adjoint orbit of maximal dimension. (Author) 8 refs

  11. Gene editing using a zinc-finger nuclease mimicking the CCR5Δ32 mutation induces resistance to CCR5-using HIV-1.

    Science.gov (United States)

    Badia, Roger; Riveira-Muñoz, Eva; Clotet, Bonaventura; Esté, José A; Ballana, Ester

    2014-07-01

    To characterize a new zinc-finger nuclease (ZFN) that targets close to the sequence of the 32 bp deletion polymorphism in the CCR5 gene, and to generate cells resistant to HIV-1 strains that use CCR5. CCR5Δ32 is a naturally occurring deletion that provides genetic resistance to R5-tropic HIV-1. The specificity and efficacy of a newly identified target for CCR5 gene editing, near the CCR5Δ32 sequence (ZFNCCR5Δ32), was assessed as well as its ability to generate cells resistant to HIV infection with reduced off-target effects. ZFNCCR5Δ32 activity was evaluated by heteroduplex formation in human K562 cells. Assessment of ZFNCCR5Δ32 specificity was analysed in silico. The yield of ZFNCCR5Δ32 in cell culture was improved by fluorescence-activated cell sorting, and the anti-HIV potency of ZFNCCR5Δ32 was measured in vitro in TZM-bl cells against HIV-1 strains. ZFNCCR5Δ32 effectively recognized the CCR5Δ32 region, inducing a frameshift of the CCR5 coding region that resulted in the complete absence of CCR5 expression of mRNA and of protein at the cell surface. CCR5 knockout cells were refractory to HIV-1 infection by the R5-using strain BaL. Unlike previous CCR5 ZFN studies, the new ZFN has no detectable off-target activity. ZFNCCR5Δ32 is a specific and efficient tool for the generation of CCR5 knockouts. Its ability to mimic the natural CCR5Δ32 phenotype in the absence of relevant off-site cutting events suggests that ZFNCCR5Δ32 might be safe in clinical research. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. An anti-CCR5 monoclonal antibody and small molecule CCR5 antagonists synergize by inhibiting different stages of human immunodeficiency virus type 1 entry

    International Nuclear Information System (INIS)

    Safarian, Diana; Carnec, Xavier; Tsamis, Fotini; Kajumo, Francis; Dragic, Tatjana

    2006-01-01

    HIV-1 coreceptors are attractive targets for novel antivirals. Here, inhibition of entry by two classes of CCR5 antagonists was investigated. We confirmed previous findings that HIV-1 isolates vary greatly in their sensitivity to small molecule inhibitors of CCR5-mediated entry, SCH-C and TAK-779. In contrast, an anti-CCR5 monoclonal antibody (PA14) similarly inhibited entry of diverse viral isolates. Sensitivity to small molecules was V3 loop-dependent and inversely proportional to the level of gp120 binding to CCR5. Moreover, combinations of the MAb and small molecules were highly synergistic in blocking HIV-1 entry, suggesting different mechanisms of action. This was confirmed by time course of inhibition experiments wherein the PA14 MAb and small molecules were shown to inhibit temporally distinct stages of CCR5 usage. We propose that small molecules inhibit V3 binding to the second extracellular loop of CCR5, whereas PA14 preferentially inhibits subsequent events such as CCR5 recruitment into the fusion complex or conformational changes in the gp120-CCR5 complex that trigger fusion. Importantly, our findings suggest that combinations of CCR5 inhibitors with different mechanisms of action will be central to controlling HIV-1 infection and slowing the emergence of resistant strains

  13. Development of experimental autoimmune uveitis: efficient recruitment of monocytes is independent of CCR2.

    Science.gov (United States)

    Dagkalis, Athanasios; Wallace, Carol; Xu, Heping; Liebau, Sebastian; Manivannan, Ayyakkannu; Stone, Michael A; Mack, Matthias; Liversidge, Janet; Crane, Isabel J

    2009-09-01

    Macrophages are major contributors to the damage occurring in the retina in experimental autoimmune uveitis (EAU). CCR2 may be needed for efficient recruitment of monocytes to an inflammatory site, and the aim of this study was to determine whether this was the case in EAU. EAU was induced and graded in C57BL/6J and CCR2(-/-) mice. Macrophage infiltration and CCR2 expression were assessed using immunohistochemistry. Retinas were examined for MCP-1 expression using RT-PCR. Rolling and infiltration of labeled bone marrow monocytes at the inflamed retinal vasculature were examined by scanning laser ophthalmoscopy and confocal microscopy, respectively. Effect of CCR2 deletion or blockade by antibody and antagonist was determined. Expression of mRNA for MCP-1 increased as EAU developed and was localized to the retina. CCR2 was associated with infiltrating macrophages. However, EAU induced in CCR2(-/-) mice was not reduced in severity, and neither was the percentage of macrophages in the retina. CCR2(-/-) monocytes, 48 hours after adoptive transfer to mice with EAU, showed no significant difference in percentage rolling or infiltration into the retina compared to WT. CCR2-independent rolling of monocytes was confirmed by CCR2 neutralizing antibody and antagonist treatment. CCR2 does not have a primary role in the recruitment of monocytes to the inflammatory site across the blood-retina barrier in well-developed EAU. Therapeutics targeting CCR2 are unlikely to be of value in treating human posterior uveitis.

  14. Marked differences in CCR5 expression and activation levels in two South African populations

    Science.gov (United States)

    Picton, Anabela C P; Shalekoff, Sharon; Paximadis, Maria; Tiemessen, Caroline T

    2012-01-01

    The chemokine receptor CCR5 is pivotal in determining an individual’s susceptibility to HIV-1 infection and rate of disease progression. To establish whether population-based differences exist in cell surface expression of CCR5 we evaluated the extent of CCR5 expression across all peripheral blood cell types in individuals from two populations, South African Africans (SAA) and South African Caucasians (SAC). Significant differences in CCR5 expression, both in number of CCR5 molecules per cell (density) and the percentage of CCR5-expressing cells, were observed between the two study groups, within all cell subsets. Most notably, the percentage of all CCR5+ cell subsets was significantly lower in SAC compared with SAA individuals (P CCR5 density was significantly higher in SAC compared with SAA individuals in CCR5+ CD8+ T-cell subsets and CCR5+ NK-cell subsets (CD56+, CD16+ CD56+ and CD56dim) (all P CCR5 expression, which are likely to impact on both susceptibility to HIV-1 infection and the rate of HIV-1 disease progression. PMID:22509959

  15. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...... time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral...... phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors....

  16. The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Møller, M; Søndergaard, H B; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We...... therefore analysed whether natalizumab-treated MS patients carrying the CCR5 Δ32 deletion allele, which results in reduced expression of CCR5 on the cell surface, had lower disease activity. METHODS: CCR5 Δ32 was analysed in 212 natalizumab-treated MS patients. RESULTS: CCR5 Δ32 status had no significant...... impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031). CONCLUSIONS: CCR5 Δ32 is not associated with lower disease...

  17. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization.

    Directory of Open Access Journals (Sweden)

    Haibo Wang

    Full Text Available Inhibition of chemokine C-C motif receptor 3 (CCR3 signaling has been considered as treatment for neovascular age-related macular degeneration (AMD. However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs that develop into choroidal neovascularization (CNV. In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF. In cultured human Műller cells exposed to eotaxin (CCL11 and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2 in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3

  18. 7 CFR 28.904 - Market news.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Market news. 28.904 Section 28.904 Agriculture..., TESTING, AND STANDARDS Cotton Classification and Market News Service for Producers Classification and Market News Services § 28.904 Market news. The Director shall cause to be distributed to producers of...

  19. Young Adolescents' Intentional Use of Science News

    Science.gov (United States)

    Tsai, Pei-Ying; Chang, Wen-Hua; Chen, Sufen; Chang, Huey-Por

    2014-01-01

    Profiling adolescent students' intentional use of science news reports can inform science news-infused instruction. This study reports on the development and validation of a Views of Science News Instruction Questionnaire (VSNIQ) designed to explore Grade 7 (12-13 years old) students' views of reasoning with respect to science news. Forty items…

  20. Diverse artikelen in Gay Amsterdam News

    NARCIS (Netherlands)

    Hekma, G.

    2002-01-01

    Vernedering, in: Gay Amsterdam News 125 (jan 2002), pp. 20-21; Webseks, zaad, zweetseks, in: Gay Amsterdam News 126 (feb 2002), pp. 30-31; Wurgseks, in: Gay Amsterdam News 127 (mrt 2002), pp. 30-31; Wijnandus Johannes Sengers (1927-2002), in: Gay Amsterdam News 133 (sept 2002), pp. 49.

  1. News and Announcements

    Science.gov (United States)

    1999-05-01

    1998 ACS Meeting in Boston he suffered a serious fall following a stroke, from which he never recovered. One of his last photographs, taken the previous day at a Journal luncheon, appears on page 1360 of the November 1998 issue. His commentary on his long career in chemistry and education appears on page 1520 of the December 1998 issue. Seaborg was a Nobel laureate, discoverer of elements, scientific advisor to presidents, former chancellor of the University of California, former chairman of the Atomic Energy Commission, chairman of the steering committee of the CHEM Study project, founder of Lawrence Hall of Science, , the list goes on and on. He was at the same time a passionate supporter of education. Seaborg published fourteen articles in the Journal between 1951 and 1998. He was interviewed in 1975 by David Ridgway as part of the Impact series (JCE 1975, 52, 70), and that interview is highly recommended reading (see supplement to this article). He received the 1994 ACS George C. Pimentel Award in Chemical Education; his award address was published in the ACS Division of Chemical Education's CHED Newsletter, Fall 1995. Memorial articles with details of his life and his scientific contributions have appeared in The New York Times (Saturday, February 27, 1999, page 1) and Chemical & Engineering News (March 8, 1999, page 29). But there is also the spirit of the man, what he believed in, what he tried to do, what he hoped he had accomplished. A sense of that can be gained from the excerpts that are reprinted below, taken first from the Impact interview and then from the award address. Ridgway: On reflection, now, out of your many contributions to chemistry, is there one that you feel has had more of an impact than others? Seaborg: The discovery of plutonium would answer that question. The impact there is probably nearly as great as any single chemical discovery. Ridgway: What was the state of the "art" in your field when you first decided to bend your energies in this

  2. News and Announcements

    Science.gov (United States)

    1999-02-01

    News from Journal House Conceptual Questions and Challenge Problems Many readers are trying to modify the way they teach and in so doing are trying to write new types of questions and problems. The Journal has a new online resource, the JCE Internet Conceptual Questions and Challenge Problems Web site, http://jchemed.chem.wisc.edu/JCEWWW/Resources/CQandChP/index.html . The site is a source of questions and problems that can be used in teaching and assessing conceptual understanding and problem solving in chemistry. Here you can find a library of free-response and multiple-choice conceptual questions and challenge problems, tips for writing these questions and problems, and a discussion of types of concept questions. This site is intended to be a means of sharing conceptual questions and challenge problems among chemical educators. It will be as inclusive as possible, and to achieve this readers need to share their questions and alert the authors to references or Web sites. The screen captures shown below should provide a feeling for what you will find when you visit the site. The authors, William R. Robinson and Susan C. Nurrenbern, welcome additions to the library of conceptual questions or other comments or suggestions. Contact them by email, fax, or regular mail. William R. Robinson and Susan C. Nurrenbern, Department of Chemistry, Purdue University, West Lafayette, IN 47907-1393. Bill: phone: 765/494-5453; fax: 765/494-0239; email: wrrobin@purdue.edu. Sue: phone: 765/494-0823; fax: 765/494-0239; email: nurrenbe@purdue.edu. fax: 765/494-0239. 1998 Ford Foundation Fellowships The National Research Council has announced the recipients of the 1998 fellowships for minority scholars. Three categories of fellowships were awarded: 50 to beginning graduate students, 33 to students writing their dissertations, and 28 to recent Ph.D. recipients. There were about 1,000 applicants. For information about the next competition contact the Fellowship Office of the National

  3. Epigenetic mechanisms, T-cell activation, and CCR5 genetics interact to regulate T-cell expression of CCR5, the major HIV-1 coreceptor.

    Science.gov (United States)

    Gornalusse, German G; Mummidi, Srinivas; Gaitan, Alvaro A; Jimenez, Fabio; Ramsuran, Veron; Picton, Anabela; Rogers, Kristen; Manoharan, Muthu Saravanan; Avadhanam, Nymisha; Murthy, Krishna K; Martinez, Hernan; Molano Murillo, Angela; Chykarenko, Zoya A; Hutt, Richard; Daskalakis, Demetre; Shostakovich-Koretskaya, Ludmila; Abdool Karim, Salim; Martin, Jeffrey N; Deeks, Steven G; Hecht, Frederick; Sinclair, Elizabeth; Clark, Robert A; Okulicz, Jason; Valentine, Fred T; Martinson, Neil; Tiemessen, Caroline Tanya; Ndung'u, Thumbi; Hunt, Peter W; He, Weijing; Ahuja, Sunil K

    2015-08-25

    T-cell expression levels of CC chemokine receptor 5 (CCR5) are a critical determinant of HIV/AIDS susceptibility, and manifest wide variations (i) between T-cell subsets and among individuals and (ii) in T-cell activation-induced increases in expression levels. We demonstrate that a unifying mechanism for this variation is differences in constitutive and T-cell activation-induced DNA methylation status of CCR5 cis-regulatory regions (cis-regions). Commencing at an evolutionarily conserved CpG (CpG -41), CCR5 cis-regions manifest lower vs. higher methylation in T cells with higher vs. lower CCR5 levels (memory vs. naïve T cells) and in memory T cells with higher vs. lower CCR5 levels. HIV-related and in vitro induced T-cell activation is associated with demethylation of these cis-regions. CCR5 haplotypes associated with increased vs. decreased gene/surface expression levels and HIV/AIDS susceptibility magnify vs. dampen T-cell activation-associated demethylation. Methylation status of CCR5 intron 2 explains a larger proportion of the variation in CCR5 levels than genotype or T-cell activation. The ancestral, protective CCR5-HHA haplotype bears a polymorphism at CpG -41 that is (i) specific to southern Africa, (ii) abrogates binding of the transcription factor CREB1 to this cis-region, and (iii) exhibits a trend for overrepresentation in persons with reduced susceptibility to HIV and disease progression. Genotypes lacking the CCR5-Δ32 mutation but with hypermethylated cis-regions have CCR5 levels similar to genotypes heterozygous for CCR5-Δ32. In HIV-infected individuals, CCR5 cis-regions remain demethylated, despite restoration of CD4+ counts (≥800 cells per mm(3)) with antiretroviral therapy. Thus, methylation content of CCR5 cis-regions is a central epigenetic determinant of T-cell CCR5 levels, and possibly HIV-related outcomes.

  4. Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.

    Science.gov (United States)

    Frossard, Jean Louis; Lenglet, Sébastien; Montecucco, Fabrizio; Steffens, Sabine; Galan, Katia; Pelli, Graziano; Spahr, Laurent; Mach, Francois; Hadengue, Antoine

    2011-05-01

    Acute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4. The severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining. The authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates. These results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.

  5. HIV-1 Escape from the CCR5 Antagonist Maraviroc Associated with an Altered and Less-Efficient Mechanism of gp120-CCR5 Engagement That Attenuates Macrophage Tropism▿

    Science.gov (United States)

    Roche, Michael; Jakobsen, Martin R.; Sterjovski, Jasminka; Ellett, Anne; Posta, Filippo; Lee, Benhur; Jubb, Becky; Westby, Mike; Lewin, Sharon R.; Ramsland, Paul A.; Churchill, Melissa J.; Gorry, Paul R.

    2011-01-01

    Maraviroc (MVC) inhibits the entry of human immunodeficiency virus type 1 (HIV-1) by binding to and modifying the conformation of the CCR5 extracellular loops (ECLs). Resistance to MVC results from alterations in the HIV-1 gp120 envelope glycoproteins (Env) enabling recognition of the drug-bound conformation of CCR5. To better understand the mechanisms underlying MVC resistance, we characterized the virus-cell interactions of gp120 from in vitro-generated MVC-resistant HIV-1 (MVC-Res Env), comparing them with those of gp120 from the sensitive parental virus (MVC-Sens Env). In the absence of the drug, MVC-Res Env maintains a highly efficient interaction with CCR5, similar to that of MVC-Sens Env, and displays a relatively modest increase in dependence on the CCR5 N terminus. However, in the presence of the drug, MVC-Res Env interacts much less efficiently with CCR5 and becomes critically dependent on the CCR5 N terminus and on positively charged elements of the drug-modified CCR5 ECL1 and ECL2 regions (His88 and His181, respectively). Structural analysis suggests that the Val323 resistance mutation in the gp120 V3 loop alters the secondary structure of the V3 loop and the buried surface area of the V3 loop–CCR5 N terminus interface. This altered mechanism of gp120-CCR5 engagement dramatically attenuates the entry of HIV-1 into monocyte-derived macrophages (MDM), cell-cell fusion activity in MDM, and viral replication capacity in MDM. In addition to confirming that HIV-1 escapes MVC by becoming heavily dependent on the CCR5 N terminus, our results reveal novel interactions with the drug-modified ECLs that are critical for the utilization of CCR5 by MVC-Res Env and provide additional insights into virus-cell interactions that modulate macrophage tropism. PMID:21345957

  6. "I Have Good News and Bad News:" The Effects of Power Imbalances and Physical Distance on News-givers' Use of Blended News Delivery

    OpenAIRE

    Legg, Angela M.

    2013-01-01

    People dislike giving bad news, and one strategy they use to ease the process is to pair bad news with some good news, a phenomenon called blended news delivery. Often, blended news arrives from people in power positions such as physicians, managers, or teachers. But followers also find themselves needing to give bad news to those in higher power positions. Similarly, people can choose how they deliver bad news, such as in person or over email. The current study brings much needed empirical a...

  7. TV Producer Juggles Daily News.

    Science.gov (United States)

    Brennan, Bill

    1989-01-01

    Brennan discusses the daily activities required in the production of a television news show. In "The Not-So-Glamorous Life of a TV Reporter," Linda Yu describes the time and effort required to become a television reporter. (LS)

  8. Creative Cycling of News Professionals

    Directory of Open Access Journals (Sweden)

    Astrid Gynnild, PhD.

    2007-03-01

    Full Text Available The theory of creative cycling emerged from my PhD study of news professionals in Norway. The study was carried out according to classic grounded theory principles (Glaser and Strauss 1967, Glaser 1978, 1998, 2001, 2005, and the area of interest was the performance of news journalism in the multimedia age. The theory runs counter to widespread tendencies of industrial age thinking in news media. It emphasizes news professionals’ search for meaning in their daily work, and suggests that their main concern is self-fulfillment through original contribution. The dilemma and resolution, creative cycling, is a basic social process continuously going within inner and outer framings. It consists of three interrelated dimensions: productive processing, breaks and shifts and inspirational looping.

  9. RHYTHM STRUCTURE IN NEWS READING

    Directory of Open Access Journals (Sweden)

    Lluís Mas Manchón

    2013-06-01

    Full Text Available Rhythm is central to news reading in radio and television programs. This paper proposes a three level structure for rhythm in news discourse. It gives a comprehensive definition of rhythm and types of rhythm. Firstly, the Base Rhythm Structure consists of semantic and pragmatic rhythmic accents, coincident with very specific words. Secondly, these accents are grouped together according to type, frequency and order, thereby configuring three types of “rhythmic units” (the Internal Rhythm Structure: starting, main and end units. A last structure level presents four discursive factors that are very important in integrating the overall time structure of news announcing (the Melodic Rhythm Structure. This integral structure for news announcing rhythm should be further tested in acoustic-experimental studies under the criterion of information transmission efficacy.

  10. Subprime Loans and Fake News

    DEFF Research Database (Denmark)

    Hendricks, Vincent Fella

    2017-01-01

    Could the market fundamentalism that ruled the pre-crisis financial markets of the 2000s hold lessons for how we should approach the unregulated information and news market in the digital age?......Could the market fundamentalism that ruled the pre-crisis financial markets of the 2000s hold lessons for how we should approach the unregulated information and news market in the digital age?...

  11. News, Documentary and Advocacy Journalism

    OpenAIRE

    Charles, Mathew

    2013-01-01

    This chapter examines how alternative models of journalism are emerging to counter the news values associated with the so-called mainstream media - news values, which are increasingly criticised for serving only the interests of the political and economic elite. In particular, this chapter looks at advocacy journalism, which focuses on a shift away from objectivity towards the arguably more ethical practice of attachment. The neutral and detached reporter, who remains outside of events and re...

  12. News from Council

    CERN Multimedia

    2016-01-01

    With this message I would like to share with you some highlights of this week’s Council meetings.   A major topic was the approval of CERN’s Medium Term Plan (MTP) 2017-2021, along with the budget for 2017. In approving the document, Council expressed its very strong support for the research programme the MTP outlines for the coming years.  Another important topic this week was the formal approval of the High Luminosity LHC project, HL-LHC. This comes as extremely good news not only for CERN, but also for particle physics globally. HL-LHC is the top priority of the European Strategy for Particle Physics in its 2013 update, and is part of the 2016 roadmap of the European Strategy Forum on Research Infrastructures, ESFRI. It was also identified as a priority in the US P5 strategy process, and in Japan’s strategic vision for the field. It secures CERN’s future until 2035, and ensures that we will achieve the maximum scientific return on the investment...

  13. News from the world

    International Nuclear Information System (INIS)

    Anon.

    2011-01-01

    This document gathers pieces of information from around the world concerning the nuclear sector. Among which were the following. Saudi-Arabia projects to build 16 nuclear reactors till 2020. In Pakistan the third reactor has entered into service, this reactor (Chashma-2, 330 MW) is a PWR-type reactor designed by CNNC (China National Nuclear Corporation). Areva Newport News LLC has postponed to a later date the construction of a plant dedicated to manufacturing big components like reactor vessels or vessel heads. Areva and Rhodia have signed an agreement for a better valorization of deposits involving uranium and rare earth elements. Bulgaria has inaugurated a new storage center for nuclear wastes. Areva has launched the construction of a plant dedicated to the production of Pb-212, an isotope used in the treatment of some cancers. A worker died of a fall on the building site of Flamanville-3. According to COMARE (Committee on Medical Aspects of Radiation in the Environment) there is no relationship between the child leukemia and the presence of nuclear power plants in U.K. Siemens has been condemned to pay 0.648 billion euros to Areva as a compensation for the breach of the shareholder pact. Rosatom has created Rosatom Overseas that will be in charge of financing, building, operating and even owning nuclear power plants on foreign soil. 'Electricite de France' has presented its trends for the next decade. (A.C.)

  14. New Bulletin: Latest News

    CERN Document Server

    2005-01-01

    The paper version of the CERN Bulletin will be published twice a month with effect from 18 April 2005. The electronic version will be updated weekly. This year will see many changes in the Bulletin, designed to make it more economical, more compact and more attractive. From 18 April the paper version of the Bulletin will be published twice monthly, so we shall have to stop calling it the "Weekly". The purpose of this change in publication frequency is to redistribute the resources of the Publications Section of the Communications Group so that it can produce new brochures for the general public. However, so as not to compromise on topicality and communication of information, the Official News and General Information sections, the Pension Fund and training announcements and the seminar schedule will continue to be updated weekly. If you have signed up to be informed of the updates, you will continue to receive a weekly e-mail reminding you that the electronic version of the Bulletin has been updated. Offici...

  15. News from EUPHA

    Directory of Open Access Journals (Sweden)

    EUPHA 17th European Conference on Public Health

    2009-06-01

    Full Text Available It is very good news for Italian participation at this year’s EUPHA meeting, which will be held in Lodz (Poland. From 25 to 28 November the joint annual conference EUPHA-ASPHER will see a peaceful “invasion” from Italy. Out of the 63 Italian abstracts submitted to the conference organisers, only 5 (7.9% were rejected. Overall, 11.6% of all of the accepted abstracts are Italian, 9.8% of the oral presentations and 13% of the poster presentations. These results pay testimony to the high quality of European public health research and practice reached in several fields and settings (academic, public health regional agencies, and local health units. Highlights from Italy include the ongoing work in the field of infectious disease control, Stefania Bruno (Catholic University will present the Roman experience of Tubercolosis surveillance in the homeless. Maria De Giusti (Sapienza University presents “Knowledge, attitudes and behaviour towards Methicillin-resistant Staphylococcus aureus skin infections and S. aureus nasal colonisation”; while Chiara de Waure (Catholic University will present “Rapid screening tests for MRSA carriage at hospital admission: a systematic review”.

  16. The molecular cloning and functional expression of the dog CCR5.

    Science.gov (United States)

    Mosley, Michael; Pullen, Sarah; Botham, Andrew; Gray, Andrew; Napier, Carolyn; Mansfield, Roy; Holbrook, Mark

    2006-10-15

    Activation of CCR5 by specific chemokines is involved in the regulation of the immunological response of leukocytes at sites of inflammation. In addition, CCR5 serves as a fusion co-factor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1). Consequently, several CCR5 antagonists are currently in development for the treatment of HIV-1 infection. The dog CCR5 gene was cloned in order to characterise the chemokine binding site of the dog receptor for comparison across species. The deduced amino acid sequence of the dog CCR5 has close homology to the human receptor (80% identity). A HEK-293 cell line expressing the dog recombinant receptor was generated and immunoblot analysis with an anti-human CCR5 antibody revealed a 58kDa band in the cell lysate. In functional calcium signalling assays, the CCR5 endogenous ligands MIP-1alpha, MIP-1beta and RANTES evoked a robust response in the dog recombinant CCR5 cells. In a CRE-Luc (cAMP response element-luciferase) reporter gene assay, MIP-1beta (0.01-30nM) produced concentration-dependent inhibition of forskolin induced elevation in cAMP levels, and was equipotent in dog, human and macaque recombinant CCR5 cells (EC(50) 0.4, 0.21 and 0.47nM, respectively). These data suggest that chemokine signalling is conserved in the dog CCR5.

  17. Suppression of CCR impacts metabolite profile and cell wall composition in Pinus radiata tracheary elements.

    Science.gov (United States)

    Wagner, Armin; Tobimatsu, Yuki; Goeminne, Geert; Phillips, Lorelle; Flint, Heather; Steward, Diane; Torr, Kirk; Donaldson, Lloyd; Boerjan, Wout; Ralph, John

    2013-01-01

    Suppression of the lignin-related gene cinnamoyl-CoA reductase (CCR) in the Pinus radiata tracheary element (TE) system impacted both the metabolite profile and the cell wall matrix in CCR-RNAi lines. UPLC-MS/MS-based metabolite profiling identified elevated levels of p-coumaroyl hexose, caffeic acid hexoside and ferulic acid hexoside in CCR-RNAi lines, indicating a redirection of metabolite flow within phenylpropanoid metabolism. Dilignols derived from coniferyl alcohol such as G(8-5)G, G(8-O-4)G and isodihydrodehydrodiconiferyl alcohol (IDDDC) were substantially depleted, providing evidence for CCR's involvement in coniferyl alcohol biosynthesis. Severe CCR suppression almost halved lignin content in TEs based on a depletion of both H-type and G-type lignin, providing evidence for CCR's involvement in the biosynthesis of both lignin types. 2D-NMR studies revealed minor changes in the H:G-ratio and consequently a largely unchanged interunit linkage distribution in the lignin polymer. However, unusual cell wall components including ferulate and unsaturated fatty acids were identified in TEs by thioacidolysis, pyrolysis-GC/MS and/or 2D-NMR in CCR-RNAi lines, providing new insights into the consequences of CCR suppression in pine. Interestingly, CCR suppression substantially promoted pyrolytic breakdown of cell wall polysaccharides, a phenotype most likely caused by the incorporation of acidic compounds into the cell wall matrix in CCR-RNAi lines.

  18. CCR5 Conformations Are Dynamic and Modulated by Localization, Trafficking and G Protein Association

    Science.gov (United States)

    Flegler, Ayanna J.; Cianci, Gianguido C.; Hope, Thomas J.

    2014-01-01

    CCR5 acts as the principal coreceptor during HIV-1 transmission and early stages of infection. Efficient HIV-1 entry requires a series of processes, many dependent on the conformational state of both viral envelope protein and cellular receptor. Monoclonal antibodies (MAbs) are able to identify different CCR5 conformations, allowing for their use as probes to distinguish CCR5 populations. Not all CCR5 MAbs are able to reduce HIV-1 infection, suggesting the use of select CCR5 populations for entry. In the U87.CD4.CCR5-GFP cell line, we used such HIV-1-restricting MAbs to probe the relation between localization, trafficking and G protein association for individual CCR5 conformations. We find that CCR5 conformations not only exhibit different localization and abundance patterns throughout the cell, but that they also display distinct sensitivities to endocytosis inhibition. Using chemokine analogs that vary in their HIV-1 inhibitory mechanisms, we also illustrate that responses to ligand engagement are conformation-specific. Additionally, we provide supporting evidence for the select sensitivity of conformations to G protein association. Characterizing the link between the function and dynamics of CCR5 populations has implications for understanding their selective targeting by HIV-1 and for the development of inhibitors that will block CCR5 utilization by the virus. PMID:24586501

  19. Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes.

    Science.gov (United States)

    Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function.

  20. Effects of CCR5-Delta32 and CCR2-64I alleles on HIV-1 disease progression: the protection varies with duration of infection

    NARCIS (Netherlands)

    Mulherin, Stephanie A.; O'Brien, Thomas R.; Ioannidis, John P.; Goedert, James J.; Buchbinder, Susan P.; Coutinho, Roel A.; Jamieson, Beth D.; Meyer, Laurence; Michael, Nelson L.; Pantaleo, Giuseppe; Rizzardi, G. Paolo; Schuitemaker, Hanneke; Sheppard, Haynes W.; Theodorou, Ioannis D.; Vlahov, David; Rosenberg, Philip S.

    2003-01-01

    OBJECTIVE: To examine temporal variation in the effects of CCR5-Delta32 and CCR2-64I chemokine receptor gene polymorphisms on HIV-1 disease progression. DESIGN: Pooled analysis of individual patient data from 10 cohorts of HIV-1 seroconverters from the United States, Europe, and Australia. METHODS:

  1. Causal pathways of the effects of age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on AIDS development

    NARCIS (Netherlands)

    Geskus, Ronald B.; Meyer, Laurence; Hubert, Jean-Baptiste; Schuitemaker, Hanneke; Berkhout, Ben; Rouzioux, Christine; Theodorou, Ioannis D.; Delfraissy, Jean-François; Prins, Maria; Coutinho, Roel A.

    2005-01-01

    OBJECTIVE: To investigate the causal pathways by which age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles influence progression to AIDS. DESIGN: Analysis of follow-up data from 2 cohort studies among homosexual men (n=400), having >10 years of follow-up. METHODS: The effects of the 4

  2. Distribution of CCR5-Delta32, CCR5 promoter 59029 A/G, CCR2-64I and SDF1-3'A genetic polymorphisms in HIV-1 infected and uninfected patients in the west region of Cameroon.

    Science.gov (United States)

    Nkenfou, Céline Nguefeu; Mekue, Linda Chapdeleine Mouafo; Nana, Christelle Tafou; Kuiate, Jules Roger

    2013-07-23

    Genetic variants of the genes encoding human immunodeficiency virus-1 (HIV-1) co-receptors and their ligands, like CC-chemokine receptor 5 delta 32 mutation (CCR5-Delta32), CCR5 promoter A/G (Adenine/Guanine), CC-chemokine receptor 2 mutation 64 isoleucine (CCR2-64I) and the stromal cell-derived factor 3'A mutation (SDF1-3'A), are involved in the susceptibility to HIV-1 infection and progression. The prevalence of these mutations varies by region. However, little is known about their distribution in the population of Dschang, located in the west region of Cameroon. The prevalence of HIV in the west region of Cameroon is lower than elsewhere in Cameroon. The objectives of this study were to determine the distribution of four AIDS Related Gene (ARG) variants in HIV-infected and non-infected population of Cameroon especially in the west region and to estimate the contribution of these variants to the susceptibility or resistance to HIV infection. We also aimed to evaluate the effectiveness of genotyping using dried blood spot (DBS) samples. A total of 179 participants were recruited from two hospitals in Dschang in the west region of Cameroon. Their genotypes for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3'A were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphisms. A total of 179 participants were enrolled in the study. Among them, 32 (17.9%) were HIV positive and 147 (82.1%) were HIV negative. The allelic frequencies of these genes were: 0%, 49.72%, 17.6% and 100% respectively for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3'A. No individual was found to carry the CCR5-Delta 32 mutation. All participants recruited were heterozygous for the SDF1-3'A allele. Our data suggest that the CCR5-Delta32 cannot account for the protection as it was completely absent in our population. SDF1-3'A variants, may be in association with other polymorphisms, may account for the overall protection from HIV-1 infection

  3. Solution structure of LC4 transmembrane segment of CCR5.

    Directory of Open Access Journals (Sweden)

    Kazuhide Miyamoto

    Full Text Available CC-chemokine receptor 5 (CCR5 is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1. The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  4. Solution structure of LC4 transmembrane segment of CCR5.

    Science.gov (United States)

    Miyamoto, Kazuhide; Togiya, Kayo

    2011-01-01

    CC-chemokine receptor 5 (CCR5) is a specific co-receptor allowing the entry of human immunodeficiency virus type 1 (HIV-1). The LC4 region in CCR5 is required for HIV-1 entry into the cells. In this study, the solution structure of LC4 in SDS micelles was elucidated by using standard 1H two-dimensional NMR spectroscopy, circular dichroism, and fluorescence quenching. The LC4 structure adopts two helical structures, whereas the C-terminal part remains unstructured. The positions in which LC4 binds to the HIV-1 inhibitory peptide LC5 were determined by docking calculations in addition to NMR data. The poses showed the importance of the hydrophobic interface of the assembled structures. The solution structure of LC4 elucidated in the present work provides a structural basis for further studies on the HIV-1 inhibitory function of the LC4 region.

  5. CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis

    DEFF Research Database (Denmark)

    Holst, P J; Orskov, C; Qvortrup, K

    2007-01-01

    CCR5 and CXCR3 are important molecules in regulating the migration of activated lymphocytes. Thus, the majority of tissue-infiltrating T cells found in the context of autoimmune conditions and viral infections express CCR5 and CXCR3, and the principal chemokine ligands are expressed within inflamed...... tissues. Accordingly, intervention studies have pointed to nonredundant roles of these receptors in models of allograft rejection, viral infection, and autoimmunity. In spite of this, considerable controversy exists, with many studies failing to support a role for CCR5 or CXCR3 in disease pathogenesis....... One possible explanation is that different chemokine receptors may take over in the absence of any individual receptor, thus rendering individual receptors redundant. We have attempted to address this issue by analyzing CCR5(-/-), CXCR3(-/-), and CCR5/CXCR3(-/-) mice with regard to virus-induced liver...

  6. The architecture of the Schizosaccharomyces pombe CCR4-NOT complex

    Science.gov (United States)

    Ukleja, Marta; Cuellar, Jorge; Siwaszek, Aleksandra; Kasprzak, Joanna M.; Czarnocki-Cieciura, Mariusz; Bujnicki, Janusz M.; Dziembowski, Andrzej; M. Valpuesta, Jose

    2016-01-01

    CCR4-NOT is a large protein complex present both in cytoplasm and the nucleus of eukaryotic cells. Although it is involved in a variety of distinct processes related to expression of genetic information such as poly(A) tail shortening, transcription regulation, nuclear export and protein degradation, there is only fragmentary information available on some of its nine subunits. Here we show a comprehensive structural characterization of the native CCR4-NOT complex from Schizosaccharomyces pombe. Our cryo-EM 3D reconstruction of the complex, combined with techniques such as immunomicroscopy, RNA-nanogold labelling, docking of the available high-resolution structures and models of different subunits and domains, allow us to propose its full molecular architecture. We locate all functionally defined domains endowed with deadenylating and ubiquitinating activities, the nucleus-specific RNA-interacting subunit Mmi1, as well as surfaces responsible for protein–protein interactions. This information provides insight into cooperation of the different CCR4-NOT complex functions. PMID:26804377

  7. CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus.

    Science.gov (United States)

    Kang, HyunJun; Minder, Petra; Park, Mi Ae; Mesquitta, Walatta-Tseyon; Torbett, Bruce E; Slukvin, Igor I

    2015-12-15

    The chemokine (C-C motif) receptor 5 (CCR5) serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs) using CRISPR/Cas9 with single and dual guide RNAs (gRNAs). Following CRISPER/Cas9-mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications.

  8. CCR5 Disruption in Induced Pluripotent Stem Cells Using CRISPR/Cas9 Provides Selective Resistance of Immune Cells to CCR5-tropic HIV-1 Virus

    Directory of Open Access Journals (Sweden)

    HyunJun Kang

    2015-01-01

    Full Text Available The chemokine (C-C motif receptor 5 (CCR5 serves as an HIV-1 co-receptor and is essential for cell infection with CCR5-tropic viruses. Loss of functional receptor protects against HIV infection. Here, we report the successful targeting of CCR5 in GFP-marked human induced pluripotent stem cells (iPSCs using CRISPR/Cas9 with single and dual guide RNAs (gRNAs. Following CRISPER/Cas9-mediated gene editing using a single gRNA, 12.5% of cell colonies demonstrated CCR5 editing, of which 22.2% showed biallelic editing as determined by a Surveyor nuclease assay and direct sequencing. The use of dual gRNAs significantly increased the efficacy of CCR5 editing to 27% with a biallelic gene alteration frequency of 41%. To ensure the homogeneity of gene editing within cells, we used single cell sorting to establish clonal iPSC lines. Single cell-derived iPSC lines with homozygous CCR5 mutations displayed the typical characteristics of pluripotent stem cells and differentiated efficiently into hematopoietic cells, including macrophages. Although macrophages from both wild-type and CCR5-edited iPSCs supported CXCR4-tropic virus replication, macrophages from CCR5-edited iPSCs were uniquely resistant to CCR5-tropic virus challenge. This study demonstrates the feasibility of applying iPSC technology for the study of the role of CCR5 in HIV infection in vitro, and generation of HIV-resistant cells for potential therapeutic applications.

  9. News of the world

    International Nuclear Information System (INIS)

    Anon.

    2011-01-01

    This document gathers a series of news from the nuclear industry and throughout the world. The most relevant are the following. The temperature of the Fukushima damaged reactors is below 100 Celsius degrees but it is suspected that the corium of the reactor 1 has gone through the reactor vessel and has reacted with the concrete of the reactor containment over a 65 cm depth. The EPR (European pressurized reactor) has received a temporal certification from the British Nuclear Safety Authority. 3 sites have been pre-selected for the construction of the first nuclear power station in Poland. ANDRA (French National Agency for the Management of Radioactive Wastes) has been allowed to use the Bure underground laboratory till 2030. 6 sites for the disposal in deep geological layers of radioactive wastes have been preselected in Switzerland. The very weak air contamination by I 131 that was detected in France in november had no sanitary impact, this contamination was due to releases in the atmosphere at the Institute of Isotopes in Budapest. The European Commission has proposed to give an extra support of 500 million euros to the dismantling of reactors in Bulgaria, Lithuania and Slovakia. Westinghouse Electric Company has signed an agreement with the engineering company DBD for the development of the AP1000 reactor in the United-Kingdom. The IRSN (French Institute for Radiation Protection and Nuclear Safety) and the Vuez firm have inaugurated in Slovakia the Viktoria Rig that will simulate the consequences in the reactor containment of a break of the primary cooling system. (A.C.)

  10. News of the world

    International Nuclear Information System (INIS)

    Anon.

    2012-01-01

    This document gathers pieces of news from the nuclear industry around the world. The most relevant are the following. EDF has inaugurated a logistic hub for the supply of spare parts for its 58 operating reactors. Russia has opened a new site to store spent fuels from RBMK reactors. This site is located at Zheleznogorsk near Krasnoiarsk in Siberia. The capacity of the La Hague fuel reprocessing plant is 1700 tonnes a year but the plant processes only between 800 and 1000 tones because most of its foreign contracts have come to an end and have not been renewed. In 2012 the plant is expected to process 1003 tonnes for EDF and 12 tonnes for The Netherlands. AREVA has delivered to the CNNC Chinese company 700 fuel assemblies and 800 control rod clusters. The French Institute for Radioprotection and Nuclear Safety (IRSN) said that there was neither health nor environmental hazards on French soil due to the Fukushima accident. The French Academy of Sciences has highlighted the least sanitary impact of nuclear power compared to other energies. The American Nuclear Safety Association has stated that the American nuclear power plants are safe and that the probability of a severe accident is very low. A new study shows an excess of cases of leukemia near nuclear power stations in France. This study rests on very few statistical cases. An opinion survey in the United Kingdom shows that the construction of nuclear power stations is considered as the best investment in infrastructures. EDF has planned to recruit in 2012 about 6000 people essentially in the nuclear sector. The Netherlands government has given its consent for the construction of the high flux reactor Pallas on the Petten site, this reactor will replace the HFR whose lifetime is over 50 years. (A.C.)

  11. Exploring Digital News Publishing Business Models

    DEFF Research Database (Denmark)

    Lindskow, Kasper

    in digital news publishing ecologies and of the production networks that are associated with the co-production of digital news offerings. The theoretical model and methodology developed in the dissertation are used to explore the American digital news publishing ecology and the strategies that 41 different...... of the traditional business models poses an existential threat to news publishing and has given rise to a continuing struggle among news publishers to design digital business models that will be sustainable in the future. This dissertation argues that a central and underresearched aspect of digital news publishing...... business models concerns the production networks that support the co-production of digital news offerings. To fill this knowledge gap, this dissertation explores the strategic design of the digital news publishing production networks that are associated with HTML-based news offerings on the open Web...

  12. Biased signaling of G protein-coupled receptors - From a chemokine receptor CCR7 perspective

    DEFF Research Database (Denmark)

    Jørgensen, Astrid Sissel; Rosenkilde, Mette M; Hjortø, Gertrud M

    2018-01-01

    findings related to ligand- and tissue-biased signaling of CCR7 and summarize what is known about bias at other chemokine receptors. CCR7 is expressed by a subset of T-cells and by mature dendritic cells (DCs). Together with its two endogenous ligands CCL19 and CCL21, of which the carboxy terminal tail...... of CCL21 displays an extraordinarily strong glycosaminoglycan (GAG) binding, CCR7 plays a central role in coordinating the meeting between mature antigen presenting DCs and naïve T-cells which normally takes place in the lymph nodes (LNs). This process is a prerequisite for the initiation of an antigen......-specific T-cell mediated immune response. Thus CCR7 and its ligands are key players in initiating cell-based immune responses. CCL19 and CCL21 display differential interaction- and docking-modes for CCR7 leading to stabilization of different CCR7 conformations and hereby preferential activation of distinct...

  13. A highly selective CCR2 chemokine agonist encoded by human herpesvirus 6

    DEFF Research Database (Denmark)

    Lüttichau, Hans R; Clark-Lewis, Ian; Jensen, Peter Østrup

    2003-01-01

    calcium mobilization as efficiently as the endogenous chemokine ligand CCL2 through the CCR2 receptor, whereas the virally encoded chemokine did not affect any of the other 17 human chemokine receptors tested. Mutual cross-desensitization between CCL2 and vCCL4 was demonstrated in the CCR2-transfected...... cells. The affinity of vCCL4 for the CCR2 receptor was 79 nm as determined in competition binding against radioactively labeled CCL2. In the murine pre-B lymphocyte cell line L1.2 stably transfected with the CCR2 receptor, vCCL4 acted as a relatively low potency but highly efficacious chemoattractant...... being equally or more efficacious in causing cell migration than CCL2 and CCL7 and considerably more efficacious than CCL8 and CCL13. It is concluded that human herpesvirus 6 encodes a highly selective and efficacious CCR2 agonist, which will attract CCR2 expressing cells, for example macrophages...

  14. Discovery and mapping of an intracellular antagonist binding site at the chemokine receptor CCR2

    DEFF Research Database (Denmark)

    Zweemer, Annelien J M; Bunnik, Julia; Veenhuizen, Margo

    2014-01-01

    The chemokine receptor CCR2 is a G protein-coupled receptor that is involved in many diseases characterized by chronic inflammation, and therefore a large variety of CCR2 small molecule antagonists has been developed. On the basis of their chemical structures these antagonists can roughly...... be divided into two groups with most likely two topographically distinct binding sites. The aim of the current study was to identify the binding site of one such group of ligands, exemplified by three allosteric antagonists, CCR2-RA-[R], JNJ-27141491, and SD-24. We first used a chimeric CCR2/CCR5 receptor...... approach to obtain insight into the binding site of the allosteric antagonists and additionally introduced eight single point mutations in CCR2 to further characterize the putative binding pocket. All constructs were studied in radioligand binding and/or functional IP turnover assays, providing evidence...

  15. Structural refinement and prediction of potential CCR2 antagonists through validated multi-QSAR modeling studies.

    Science.gov (United States)

    Amin, Sk Abdul; Adhikari, Nilanjan; Baidya, Sandip Kumar; Gayen, Shovanlal; Jha, Tarun

    2018-01-03

    Chemokines trigger numerous inflammatory responses and modulate the immune system. The interaction between monocyte chemoattractant protein-1 and chemokine receptor 2 (CCR2) may be the cause of atherosclerosis, obesity, and insulin resistance. However, CCR2 is also implicated in other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, asthma, and neuropathic pain. Therefore, there is a paramount importance of designing potent and selective CCR2 antagonists despite a number of drug candidates failed in clinical trials. In this article, 83 CCR2 antagonists by Jhonson and Jhonson Pharmaceuticals have been considered for robust validated multi-QSAR modeling studies to get an idea about the structural and pharmacophoric requirements for designing more potent CCR2 antagonists. All these QSAR models were validated and statistically reliable. Observations resulted from different modeling studies correlated and validated results of other ones. Finally, depending on these QSAR observations, some new molecules were proposed that may exhibit higher activity against CCR2.

  16. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

    Directory of Open Access Journals (Sweden)

    Eric Lefebvre

    Full Text Available Interactions between C-C chemokine receptor types 2 (CCR2 and 5 (CCR5 and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05. At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05, and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls. CVC treatment had no notable effect on body or liver/kidney weight.CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475.

  17. Relationship between the chemokine receptor CCR5 and microglia in neurological disorders: consequences of targeting CCR5 on neuroinflammation, neuronal death and regeneration in a model of epilepsy.

    Science.gov (United States)

    Louboutin, Jean-Pierre; Strayer, David S

    2013-09-01

    Chemokines may play a role in leukocyte migration across the blood-brain barrier (BBB) during neuroinflammation and other neuropathological processes, such as epilepsy. The CC chemokine receptor 5 (CCR5) is a member of CC-chemokine receptor family that binds several chemokines, including CCL3 (macrophage inflammatory protein-1alpha, MIP-1alpha), CCL4 (macrophage inflammatory protein-1beta, MIP-1beta) and CCL5 (RANTES). The current review examines the relationship between CCR5 and the microglia in different neurological disorders and models of CNS injury. CCR5 expression is upregulated in different neurological diseases, where it is often immunolocalized in microglial cells. A multistep cascade couples CCR5 activation by chemokines to Ca(2+) increases in human microglia. Because changes in [Ca(2+)] (i) affect chemotaxis, secretion, and gene expression, pharmacologic modulation of this pathway may alter inflammatory and degenerative processes in the CNS. Consequently, targeting CCR5 by using CCR5 antagonists may attenuate critical aspects of neuroinflammation in different models of neurological disorders. To illustrate the interaction between CCR5 and microglia in the CNS, we used a model of excitotoxicity, and demonstrate the intimate involvement of CCR5 in neuron injury and inflammation attendant to kainic acid (KA)-induced neurotoxicity. CCR5 participates in neuronal injury caused by the excitotoxin, KA, brings inflammatory cells to the sites of KA-induced CNS injury, defines the extent of tissue loss after KA exposure and limits reparative responses. We used a SV40-derived vector carrying an interfering RNA (RNAi) that targets CCR5. Delivered directly to the bone marrow, this vector decreased CCR5 expression in circulating cells. Animals so treated showed greatly reduced expression of CCR5 and its ligands (MIP-1alpha and RANTES) in the CNS, including in the brain vasculature, decreased BBB leakage, demonstrated greater KA-stimulated neurogenesis and increased

  18. CCR2 mediates Helicobacter pylori-induced immune tolerance and contributes to mucosal homeostasis.

    Science.gov (United States)

    Sun, Xia; Zhang, Min; El-Zaatari, Mohamad; Huffnagle, Gray B; Kao, John Y

    2017-04-01

    We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H. pylori were examined to determine the impact of CCR2 signaling on dendritic cells function by qPCR, ELISA, and FACS analyses. Acute H. pylori infection was associated with a threefold increase in CCR2 mRNA expression in the gastric mucosa. H. pylori-infected CCR2KO mice exhibited a higher degree of mucosal inflammation, that is, increased gastritis scores and pro-inflammatory cytokine mRNA levels, but lower degree of H. pylori gastric colonization compared to infected Wt mice. Peripheral H. pylori-specific immune response measured in the CCR2KO spleen was characterized by a higher Th17 response and a lower Treg response. In vitro, CCR2KO bone marrow-derived DC was less mature and shown a lower Treg/Th17 ratio. Moreover, blockade of CCR2 signaling by MCP-1 neutralizing antibody inhibited H. pylori-stimulated bone marrow-derived DC maturation. Our results indicate that CCR2 plays an essential role in H. pylori-induced immune tolerance and shed light on a novel mechanism of CCR2-dependent DC Treg induction, which appears to be important in maintaining mucosal homeostasis during H. pylori infection. © 2016 John Wiley & Sons Ltd.

  19. CCL2 recruits T cells into the brain in a CCR2-independent manner

    DEFF Research Database (Denmark)

    Cédile, Oriane; Wlodarczyk, Agnieszka; Owens, Trevor

    2017-01-01

    CCR2, a receptor for CCL2. Expression of another receptor for CCL2, CCR4, and CXCR3, a receptor for CXCL10, which was also induced, were both increased in CCL2-treated CNS. CCR4 was expressed by neurons and astrocytes as well as CD4 T cells, and CXCR3 was expressed by CD4 and CD8 T cells. Chemokine...

  20. Pulmonary CCR2+CD4+T cells are immune regulatory and attenuate lung fibrosis development.

    Science.gov (United States)

    Milger, Katrin; Yu, Yingyan; Brudy, Eva; Irmler, Martin; Skapenko, Alla; Mayinger, Michael; Lehmann, Mareike; Beckers, Johannes; Reichenberger, Frank; Behr, Jürgen; Eickelberg, Oliver; Königshoff, Melanie; Krauss-Etschmann, Susanne

    2017-11-01

    Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2 + CD4 + T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2 + cell populations might either increase or decrease disease pathogenesis depending on their subtype. To investigate the role of CCR2 + CD4 + T cells in experimental lung fibrosis and in patients with idiopathic pulmonary fibrosis and other fibrosis. Pulmonary CCR2 + CD4 + T cells were analysed using flow cytometry and mRNA profiling, followed by in silico pathway analysis, in vitro assays and adoptive transfer experiments. Frequencies of CCR2 + CD4 + T cells were increased in experimental fibrosis-specifically the CD62L - CD44 + effector memory T cell phenotype, displaying a distinct chemokine receptor profile. mRNA profiling of isolated CCR2 + CD4 + T cells from fibrotic lungs suggested immune regulatory functions, a finding that was confirmed in vitro using suppressor assays. Importantly, adoptive transfer of CCR2 + CD4 + T cells attenuated fibrosis development. The results were partly corroborated in patients with lung fibrosis, by showing higher percentages of Foxp3 + CD25 + cells within bronchoalveolar lavage fluid CCR2 + CD4 + T cells as compared with CCR2 - CD4 + T cells. Pulmonary CCR2 + CD4 + T cells are immunosuppressive, and could attenuate lung inflammation and fibrosis. Therapeutic strategies completely abrogating CCR2-dependent signalling will therefore also eliminate cell populations with protective roles in fibrotic lung disease. This emphasises the need for a detailed understanding of the functions of immune cell subsets in fibrotic lung disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

  1. Experimental Measures of News Personalization in Google News

    DEFF Research Database (Denmark)

    Cozza, Vittoria; Hoang, Van Tien; Petrocchi, Marinella

    2016-01-01

    Search engines and social media keep trace of profile- and behavioral-based distinct signals of their users, to provide them personalized and recommended content. Here, we focus on the level of web search personalization, to estimate the risk of trapping the user into so called Filter Bubbles. Ou...... experimentation has been carried out on news, specifically investigating the Google News platform. Our results are in line with existing literature and call for further analyses on which kind of users are the target of specific recommendations by Google....

  2. News on pediatric urology

    Directory of Open Access Journals (Sweden)

    Giuseppe Masnata

    2015-10-01

    Full Text Available Pediatric urology is a pediatric speciality dedicated to the diagnosis and treatment of congenital and acquired genitourinary tract diseases. It is a speciality that is rapidly changing, thanks to the technological development that has been emerging in recent years. There have been important diagnostic and therapeutic news.Congenital anomalies of the kidneys and urinary tract (CAKUT include various entities of structural malformations that result from defects in their morphogenesis. Clinical research and genetic studies on the origins of CAKUT are quickly evolving, with significant growth of high-quality research.Management goals of CAKUT include prevention of febrile urinary tract infections (UTIs in newborns and toddles and renal injury, while minimizing the morbidity of treatment and follow-up. Treatment options include observation with or without continuous antibiotic prophylaxis (CAP and surgical correction. Now, randomized controlled studies show that children with normal urinary tracts or low-grade vesicoureteral reflux (VUR do not benefit from prophylaxis.All children with known mechanical or functional obstructions of the urinary tract are considered to have UTI. Functional obstruction often results from lower urinary tract dysfunction (LUTD of either neurogenic or non-neurogenic origin and dilating VUR.The role of bladder and bowel dysfunction (BBD in children with UTI and the long-term risk of renal scarring have shed new light on treatment strategies. Often it is BBD, rather than reflux, that causes UTI in children older than 2 years.Pediatric urology has evolved in recent years, with a greater focus on bladder and renal function, minimally invasive treatment, evidence-based interventions, and guideline adherence. Other topics in pediatric urology include urinary incontinence in children with special needs and the use of robot-assisted laparoscopic surgery (RALS in children, with advantages over conventional laparoscopic surgery

  3. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Science.gov (United States)

    Lionakis, Michail S; Fischer, Brett G; Lim, Jean K; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M

    2012-01-01

    Invasive candidiasis is the 4(th) leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo) to Ccr1(high) at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+) and Ccr1(-/-) donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+) recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+) cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

  4. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  5. Inhibition of human immunodeficiency virus replication by a dual CCR5/CXCR4 antagonist

    DEFF Research Database (Denmark)

    Princen, Katrien; Hatse, Sigrid; Vermeire, Kurt

    2004-01-01

    Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC(50)] ranging from 1.2 to 26.5 microM) in various T-cell lines, CCR5...... at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca(2+) signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca(2+) flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did...... not interfere with chemokine-induced Ca(2+) signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca(2+) signaling by itself at concentrations up to 400 microM. In freshly isolated monocytes, AMD3451 inhibited the Ca(2+) flux induced by CXCL12 and CCL4...

  6. A role for MCP-1/CCR2 in interstitial lung disease in children

    Directory of Open Access Journals (Sweden)

    Reinhardt Dietrich

    2005-08-01

    Full Text Available Abstract Background Interstitial lung diseases (ILD are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1 promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies.

  7. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

    Science.gov (United States)

    Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

    2016-01-01

    Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV. DOI: http://dx.doi.org/10.7554/eLife.20985.001 PMID:27996938

  8. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.

    Science.gov (United States)

    Zhou, Miou; Greenhill, Stuart; Huang, Shan; Silva, Tawnie K; Sano, Yoshitake; Wu, Shumin; Cai, Ying; Nagaoka, Yoshiko; Sehgal, Megha; Cai, Denise J; Lee, Yong-Seok; Fox, Kevin; Silva, Alcino J

    2016-12-20

    Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.

  9. CCR5 internalisation and signalling have different dependence on membrane lipid raft integrity.

    Science.gov (United States)

    Cardaba, Clara Moyano; Kerr, Jason S; Mueller, Anja

    2008-09-01

    The chemokine receptor, CCR5, acts as a co-receptor for human immunodeficiency virus entry into cells. CCR5 has been shown to be targeted to cholesterol- and sphingolipid-rich membrane microdomains termed lipid rafts or caveolae. Cholesterol is essential for CCL4 binding to CCR5 and for keeping the conformational integrity of the receptor. Filipin treatment leads to loss of caveolin-1 from the membrane and therefore to a collapse of the caveolae. We have found here that sequestration of membrane cholesterol with filipin did not affect receptor signalling, however a loss of ligand-induced internalisation of CCR5 was observed. Cholesterol extraction with methyl-beta-cyclodextrin (MCD) reduced signalling through CCR5 as measured by release of intracellular Ca(2+) and completely abolished the inhibition of forskolin-stimulated cAMP accumulation with no effect on internalisation. Pertussis toxin (PTX) treatment inhibited the intracellular release of calcium that is transduced via Galphai G-proteins. Depletion of cholesterol destroyed microdomains in the membrane and switched CCR5/G-protein coupling to a PTX-independent G-protein. We conclude that cholesterol in the membrane is essential for CCR5 signalling via the Galphai G-protein subunit, and that integrity of lipid rafts is not essential for effective CCR5 internalisation however it is crucial for proper CCR5 signal transduction via Galphai G-proteins.

  10. Dengue virus requires the CC-chemokine receptor CCR5 for replication and infection development.

    Science.gov (United States)

    Marques, Rafael E; Guabiraba, Rodrigo; Del Sarto, Juliana L; Rocha, Rebeca F; Queiroz, Ana Luiza; Cisalpino, Daniel; Marques, Pedro E; Pacca, Carolina C; Fagundes, Caio T; Menezes, Gustavo B; Nogueira, Maurício L; Souza, Danielle G; Teixeira, Mauro M

    2015-08-01

    Dengue is a mosquito-borne disease that affects millions of people worldwide yearly. Currently, there is no vaccine or specific treatment available. Further investigation on dengue pathogenesis is required to better understand the disease and to identify potential therapeutic targets. The chemokine system has been implicated in dengue pathogenesis, although the specific role of chemokines and their receptors remains elusive. Here we describe the role of the CC-chemokine receptor CCR5 in Dengue virus (DENV-2) infection. In vitro experiments showed that CCR5 is a host factor required for DENV-2 replication in human and mouse macrophages. DENV-2 infection induces the expression of CCR5 ligands. Incubation with an antagonist prevents CCR5 activation and reduces DENV-2 positive-stranded (+) RNA inside macrophages. Using an immunocompetent mouse model of DENV-2 infection we found that CCR5(-/-) mice were resistant to lethal infection, presenting at least 100-fold reduction of viral load in target organs and significant reduction in disease severity. This phenotype was reproduced in wild-type mice treated with CCR5-blocking compounds. Therefore, CCR5 is a host factor required for DENV-2 replication and disease development. Targeting CCR5 might represent a therapeutic strategy for dengue fever. These data bring new insights on the association between viral infections and the chemokine receptor CCR5. © 2015 John Wiley & Sons Ltd.

  11. Effect of CCR5-Δ32 heterozygosity on HIV-1 susceptibility: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Sijie Liu

    Full Text Available BACKGROUND: So far, many studies have investigated the distribution of CCR5 genotype between HIV-1 infected patients and uninfected people. However, no definite results have been put forward about whether heterozygosity for a 32-basepair deletion in CCR5 gene (CCR5-Δ32 can affect HIV-1 susceptibility. METHODS: We performed a meta-analysis of 18 studies including more than 12000 subjects for whom the CCR5-Δ32 polymorphism was genotyped. Odds ratio (OR with 95% confidence interval (CI were employed to assess the association of CCR5-Δ32 polymorphism with HIV-1 susceptibility. RESULTS: Compared with the wild-type CCR5 homozygotes, the pooled OR for CCR5-Δ32 heterozygotes was 1.02 (95%CI, 0.88-1.19 for healthy controls (HC and 0.95 (95%CI, 0.71-1.26 for exposed uninfected (EU controls. Similar results were found in stratified analysis by ethnicity, sample size and method of CCR5-Δ32 genotyping. CONCLUSIONS: The meta-analysis indicated that HIV-1 susceptibility is not significantly affected by heterozygosity for CCR5-Δ32.

  12. Targeting spare CC chemokine receptor 5 (CCR5) as a principle to inhibit HIV-1 entry.

    Science.gov (United States)

    Jin, Jun; Colin, Philippe; Staropoli, Isabelle; Lima-Fernandes, Evelyne; Ferret, Cécile; Demir, Arzu; Rogée, Sophie; Hartley, Oliver; Randriamampita, Clotilde; Scott, Mark G H; Marullo, Stefano; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando; Lagane, Bernard; Brelot, Anne

    2014-07-04

    CCR5 binds the chemokines CCL3, CCL4, and CCL5 and is the major coreceptor for HIV-1 entry into target cells. Chemokines are supposed to form a natural barrier against human immunodeficiency virus, type 1 (HIV-1) infection. However, we showed that their antiviral activity is limited by CCR5 adopting low-chemokine affinity conformations at the cell surface. Here, we investigated whether a pool of CCR5 that is not stabilized by chemokines could represent a target for inhibiting HIV infection. We exploited the characteristics of the chemokine analog PSC-RANTES (N-α-(n-nonanoyl)-des-Ser(1)-[l-thioprolyl(2), l-cyclohexylglycyl(3)]-RANTES(4-68)), which displays potent anti-HIV-1 activity. We show that native chemokines fail to prevent high-affinity binding of PSC-RANTES, analog-mediated calcium release (in desensitization assays), and analog-mediated CCR5 internalization. These results indicate that a pool of spare CCR5 may bind PSC-RANTES but not native chemokines. Improved recognition of CCR5 by PSC-RANTES may explain why the analog promotes higher amounts of β-arrestin 2·CCR5 complexes, thereby increasing CCR5 down-regulation and HIV-1 inhibition. Together, these results highlight that spare CCR5, which might permit HIV-1 to escape from chemokines, should be targeted for efficient viral blockade. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Adaptation of HIV-1 to cells with low expression of the CCR5 coreceptor.

    Science.gov (United States)

    Espy, Nicole; Pacheco, Beatriz; Sodroski, Joseph

    2017-08-01

    The binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer ((gp120/gp41) 3 ) to the receptors CD4 and CCR5 triggers virus entry into host cells. To identify Env regions that respond to CCR5 binding, HIV-1 was serially passaged on a CD4-positive canine cell line expressing progressively lower levels of CCR5. HIV-1 replication was observed in cells expressing ~1300 CCR5 molecules/cell. Env changes that conferred this low-CCR5 replication phenotype were located outside of the known CCR5-binding region of the gp120 Env subunit and did not apparently increase CCR5 binding affinity. The adaptation-associated changes, located in the gp120 α1 helix and in the gp41 HR1 heptad repeat and membrane-proximal external region (MPER), enhanced HIV-1 replication in cells at all levels of CCR5 expression. The adapted Envs exhibited a greater propensity to undergo conformational changes, as evidenced by increased exposure of conserved regions near the CD4- and CCR5-binding sites. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Rumour News and its Features

    Directory of Open Access Journals (Sweden)

    Valdas Pruskus

    2011-12-01

    Full Text Available The magic of rumours and their background are discussed in the paper. The features of rumour news, which make them interesting to an individual who can fulfil his creativity here as a creator of information and potential of a transmitter, are revealed here. It is shown that joining information “enlargers” turns an individual into the hostage of the news interchange net because of two main reasons: firstly, because of difficulties to uphold moral discretion while conveying the news, and, secondly, because of the rumour’s incompletion due to absence of a complete mechanism that makes it insatiable, requiring a new and ever “fresher” information. Factors impeding the individual’s withdrawal from the rumour’s space are analysed.

  15. Frequency of polymorphisms of genes coding for HIV-1 co-receptors CCR5 and CCR2 in a Brazilian population

    Directory of Open Access Journals (Sweden)

    Munerato Patrícia

    2003-01-01

    Full Text Available Entry of human immunodeficiency type 1 virus (HIV-1 into target cells requires both CD4and one of the chemokine receptors. Viruses predominantly use one, or occasionally both, of the major co-receptors CCR5 and CXCR4, although other receptors, including CCR2B and CCR3, function as minor co-receptors. A 32-nucleotide deletion (delta32 within the beta-chemokine receptor 5 gene (CCR5 has been described in subjects who remain uninfected despite extensive exposition to HIV-1. The heterozygous genotype delays disease progression. This allele is common among Caucasians, but has not been found in people of African or Asian ancestry. A more common transition involving a valine to isoleucine switch in transmembrane domain I of CCR2B (64I, with unknown functional consequences, was found to delay disease progression but not to reduce infection risk. As the Brazilian population consists of a mixture of several ethnic groups, we decided to examine the genotype frequency of these polymorphisms in this country. There were 11.5% CCR5 heterozygotes among the HIV-1 infected population and 12.5% among uninfected individuals, similar to data from North America and Western Europe. The prevalence of CCR2-64I homozygotes and heterozygotes was 0.06 and 15.2%, respectively, also similar to what is known for North America and Western Europe.

  16. TV 2 NEWS og nyheder

    DEFF Research Database (Denmark)

    Kartveit, Kate

    2018-01-01

    Hvordan udvikler dækningen af en nyhedsbegivenheden sig på TV2 News over 3 dage? Dette kapitel vil gennem tekstanalyse af centrale journalistiske parametre i et casestudie, undersøges hvordan den journalistiske formidling af tsunamien i Grønland udvikler sig over tid.......Hvordan udvikler dækningen af en nyhedsbegivenheden sig på TV2 News over 3 dage? Dette kapitel vil gennem tekstanalyse af centrale journalistiske parametre i et casestudie, undersøges hvordan den journalistiske formidling af tsunamien i Grønland udvikler sig over tid....

  17. How to Spot Fake News?

    Directory of Open Access Journals (Sweden)

    Çev.: Fatih Canata

    2017-03-01

    Full Text Available Critical thinking is a key skill in media and information literacy, and the mission of libraries is to educate and advocate its importance. Discussions about fake news has led to a new focus on media literacy more broadly, and the role of libraries and other education institutions in providing this. When Oxford Dictionaries announce post-truth is Word of the Year 2016, as librarians realise action is needed to educate and advocate for critical thinking – a crucial skill when navigating the information society, an infographic with eight simple steps have been prepared by IFLA to discover the verifiability of a given news-piece in front of you.

  18. News Consumption and Media Bias

    OpenAIRE

    Yi Xiang; Miklos Sarvary

    2007-01-01

    Bias in the market for news is well-documented. Recent research in economics explains the phenomenon by assuming that consumers want to read (watch) news that is consistent with their tastes or prior beliefs rather than the truth. The present paper builds on this idea but recognizes that (i) besides “biased” consumers, there are also “conscientious” consumers whose sole interest is in discovering the truth, and (ii) consistent with reality, media bias is constrained by the truth. These two fa...

  19. Preferential HIV infection of CCR6+ Th17 cells is associated with higher levels of virus receptor expression and lack of CCR5 ligands.

    Science.gov (United States)

    Alvarez, Yelina; Tuen, Michael; Shen, Guomiao; Nawaz, Fatima; Arthos, James; Wolff, Martin J; Poles, Michael A; Hioe, Catarina E

    2013-10-01

    Th17 cells are enriched in the gut mucosa and play a critical role in maintenance of the mucosal barrier and host defense against extracellular bacteria and fungal infections. During chronic human immunodeficiency virus (HIV) infection, Th17 cells were more depleted compared to Th1 cells, even when the patients had low or undetectable viremia. To investigate the differential effects of HIV infection on Th17 and Th1 cells, a culture system was used in which CCR6(+) CD4(+) T cells were sorted from healthy human peripheral blood and activated in the presence of interleukin 1β (IL-1β) and IL-23 to drive expansion of Th17 cells while maintaining Th1 cells. HIV infection of these cultures had minimal effects on Th1 cells but caused depletion of Th17 cells. Th17 loss correlated with greater levels of virus-infected cells and cell death. In identifying cellular factors contributing to higher susceptibility of Th17 cells to HIV, we compared Th17-enriched CCR6(+) and Th17-depleted CCR6(-) CD4 T cell cultures and noted that Th17-enriched CCR6(+) cells expressed higher levels of α4β7 and bound HIV envelope in an α4β7-dependent manner. The cells also had greater expression of CD4 and CXCR4, but not CCR5, than CCR6(-) cells. Moreover, unlike Th1 cells, Th17 cells produced little CCR5 ligand, and transfection with one of the CCR5 ligands, MIP-1β (CCL4), increased their resistance against HIV. These results indicate that features unique to Th17 cells, including higher expression of HIV receptors and lack of autocrine CCR5 ligands, are associated with enhanced permissiveness of these cells to HIV.

  20. The shifting cross-media news landscape

    DEFF Research Database (Denmark)

    Schrøder, Kim Christian; Steeg Larsen, Bent

    2010-01-01

    market, as a consequence of accelerating divisions between 'overview' and 'depth' news media (across print, broadcasting and the internet). The project is carried out in a partnership of university-based researchers and analysts from one of the major newspaper publishers in Denmark, and presents......The article offers new insights for democracy and for news producers by mapping the use and users of today’s cross-media news landscape, as the everyday consumption of news across the range of available news media and formats is shifting as a result of transformations of technology, culture......” of news media, a user-anchored concept which incorporates the different functionalities of the situational cross-media use of news by citizen/consumers in everyday life. Empirically the article presents the findings of a large-scale survey that traces the imminent challenges facing players in the news...

  1. NEWS: Eclipse matters (still)!

    Science.gov (United States)

    1999-05-01

    This collection of snippets has as its theme the 1999 Solar Eclipse, and covers items that might be of interest to eclipse watchers and their associates. Much information can be obtained from the national web site at http://www.eclipse.org.uk. Set up by the CLRC Rutherford Appleton Laboratory, on behalf of the UK Eclipse Group, the site is intended to keep viewers abreast of developments during the countdown to the eclipse. The list of contents includes: about eclipses; eclipse pictures; eclipse science; safety advice; latest news; and local information. There is also a wealth of images and video footage, so the site has been organized with the visitor having a small PC and modem in mind, so that the key information can be accessed as quickly as possible. Free colour leaflets containing useful details for eclipse watchers can be obtained from the Particle Physics and Astronomy Research Council. `The Sun - our local star' and `Neutrinos' are additions to PPARC's series introducing key areas of its science. They answer such questions as what the Sun is, what eclipses are, why the Sun is important and where neutrinos come from. They support the National Curriculum Key Stages 3 and 4 plus A-level physics. The A5 leaflets open out into an A2 sized double-sided wall chart and bulk quantitites are available for class sets, visitor centres, exhibitions, open days etc. A full list of PPARC materials can be found at the website http://www.pparc.ac.uk or by order from Mark Wells, PPARC, Polaris House, North Star Avenue, Swindon SN2 1SZ (fax: 01793 442002). A message has been received from George Care, Head of Physics in the Science Department at Mounts Bay School, Penzance, which we now pass on to our readers. During his application for electronic access to Physics Education via the Institute of Physics Affiliated Schools and Colleges scheme, George notes that his school is on the track of the eclipse this summer and he has invited us to pass on the details to anyone who

  2. Effects of "Good News" and "Bad News" on Newscast Image and Community Image.

    Science.gov (United States)

    Galician, Mary-Lou; Vestre, Norris D.

    1987-01-01

    Investigates whether the relative amount of bad, neutral, and good news on television has corresponding effects on viewers' image of the community depicted and of the carrying newscast. Concludes that bad news creates a bad image for the community but that good news does not produce a more favorable image than neutral news. (MM)

  3. Implementation of news module for news client based on ApiCloud

    Directory of Open Access Journals (Sweden)

    Fu Xin

    2017-01-01

    Full Text Available With the development of new media technology, news client has become the main battlefield of news browsing. Based on the ApiCloud hybrid development platform, this paper uses HTML, JavaScript and other technologies to develop the mobile client news module, and uses WAMP integrated development environment to build a news publishing system on the server side.

  4. Arousing news characteristics in Dutch television news 1990-2004: an exploration of competitive strategies

    NARCIS (Netherlands)

    Hendriks Vettehen, P.; Beentjes, J.; Nuijten, K.; Peeters, A.

    2011-01-01

    This study investigates the processes by which competition in the television news market might promote the presence of arousing characteristics in television news. A total of 3,024 news stories from six Dutch television news programs over the period 1990 to 2004 were investigated through content

  5. Arousing news characteristics in Dutch television news 1990-2004: An exploration of competitive strategies

    NARCIS (Netherlands)

    Hendriks Vettehen, P.G.J.; Beentjes, J.W.J.; Nuijten, C.M.; Peeters, A.L.

    2011-01-01

    This study investigates the processes by which competition in the television news market might promote the presence of arousing characteristics in television news. A total of 3,024 news stories from six Dutch television news programs over the period 1990 to 2004 were investigated through content

  6. Implementation of news module for news client based on ApiCloud

    OpenAIRE

    Fu Xin; Liang Yu; Cao Sanxing; Gu Hongbo

    2017-01-01

    With the development of new media technology, news client has become the main battlefield of news browsing. Based on the ApiCloud hybrid development platform, this paper uses HTML, JavaScript and other technologies to develop the mobile client news module, and uses WAMP integrated development environment to build a news publishing system on the server side.

  7. Exploiting Tri-Relationship for Fake News Detection

    OpenAIRE

    Shu, Kai; Wang, Suhang; Liu, Huan

    2017-01-01

    Social media for news consumption is becoming popular nowadays. The low cost, easy access and rapid information dissemination of social media bring benefits for people to seek out news timely. However, it also causes the widespread of fake news, i.e., low-quality news pieces that are intentionally fabricated. The fake news brings about several negative effects on individual consumers, news ecosystem, and even society trust. Previous fake news detection methods mainly focus on news contents fo...

  8. Delivering bad news in emergency care medicine

    OpenAIRE

    Maynard, Douglas W.

    2016-01-01

    Forecasting is a strategy for delivering bad news and is compared to two other strategies, stalling and being blunt. Forecasting provides some warning that bad news is forthcoming without keeping the recipient in a state of indefinite suspense (stalling) or conveying the news abruptly (being blunt). Forecasting appears to be more effective than stalling or being blunt in helping a recipient to “realize” the bad news because it involves the deliverer and recipient in a particular social relati...

  9. Emotional Mining: Tagging Emoticons to Online News

    Science.gov (United States)

    Kasinathan, Vinothini; Mustapha, Aida; Zhi Yong, Lee; Aida Zamnah, Z. A.

    2017-08-01

    This paper presents an emotion mining system, which assigns emoticons to newspaper articles into a pre-defined emotion category based on the underlying emotion in the news. Next, the system makes recommendation to the reader by tagging the news headline with the respective emoticons. Users are then able to decide whether to read the news based on the emoticons provided. The system also provides a filter for the users to choose the category of news to read following the emoticons.

  10. Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

    Science.gov (United States)

    Toyoda, Hiromi; Honda, Yoshiko; Tanaka, Susumu; Miyagawa, Taku; Honda, Makoto; Honda, Kazuki; Tokunaga, Katsushi; Kodama, Tohru

    2017-01-01

    Narcolepsy is caused by the loss of hypocretin (Hcrt) neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif) receptor 3 (CCR3) as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO) mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT) littermates. Intraperitoneal injection of lipopolysaccharide (LPS) promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

  11. Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.

    Directory of Open Access Journals (Sweden)

    Hiromi Toyoda

    Full Text Available Narcolepsy is caused by the loss of hypocretin (Hcrt neurons and is associated with multiple genetic and environmental factors. Although abnormalities in immunity are suggested to be involved in the etiology of narcolepsy, no decisive mechanism has been established. We previously reported chemokine (C-C motif receptor 3 (CCR3 as a novel susceptibility gene for narcolepsy. To understand the role of CCR3 in the development of narcolepsy, we investigated sleep-wake patterns of Ccr3 knockout (KO mice. Ccr3 KO mice exhibited fragmented sleep patterns in the light phase, whereas the overall sleep structure in the dark phase did not differ between Ccr3 KO mice and wild-type (WT littermates. Intraperitoneal injection of lipopolysaccharide (LPS promoted wakefulness and suppressed both REM and NREM sleep in the light phase in both Ccr3 KO and WT mice. Conversely, LPS suppressed wakefulness and promoted NREM sleep in the dark phase in both genotypes. After LPS administration, the proportion of time spent in wakefulness was higher, and the proportion of time spent in NREM sleep was lower in Ccr3 KO compared to WT mice only in the light phase. LPS-induced changes in sleep patterns were larger in Ccr3 KO compared to WT mice. Furthermore, we quantified the number of Hcrt neurons and found that Ccr3 KO mice had fewer Hcrt neurons in the lateral hypothalamus compared to WT mice. We found abnormalities in sleep patterns in the resting phase and in the number of Hcrt neurons in Ccr3 KO mice. These observations suggest a role for CCR3 in sleep-wake regulation in narcolepsy patients.

  12. Association between HIV-1 tropism and CCR5 human haplotype E in a Caucasian population.

    Science.gov (United States)

    Huik, Kristi; Avi, Radko; Uibopuu, Helen; Pauskar, Merit; Margus, Tõnu; Karki, Tõnis; Krispin, Tõnu; Kool, Piret; Rüütel, Kristi; Talu, Ave; Abel-Ollo, Katri; Uusküla, Anneli; Carrillo, Andrew; He, Weijing; Ahuja, Sunil K; Lutsar, Irja

    2014-07-01

    The influence of the diversity of CCR5 on HIV susceptibility and disease progression has been clearly demonstrated but how the variability of this gene influences the HIV tropism is poorly understood. We investigated whether CCR5 haplotypes are associated with HIV tropism in a Caucasian population. We evaluated 161 HIV-positive subjects in a cross-sectional study. CCR5 haplotypes were derived after genotyping 9 CCR2-CCR5 polymorphisms. The HIV subtype was determined by phylogenetic analysis using the maximum likelihood method and viral tropism by the genotypic tropism assay (geno2pheno). Associations between CCR5 haplotypes and viral tropism were determined using logistic regression analyses. Samples from 500 blood donors were used to evaluate the representativeness of HIV-positives in terms of CCR5 haplotype distribution. The distribution of CCR5 haplotypes was similar in HIV-positive subjects and blood donors. The majority of viruses (93.8%) belonged to HIV-1 CRF06_cpx; 7.5% were X4, and the remaining were R5 tropic. X4 tropic viruses were over represented among people with CCR5 human haplotype E (HHE) compared with those without this haplotype (13.0% vs 1.4%; P = 0.006). People possessing CCR5 HHE had 11 times increased odds (odds ratio = 11.00; 95% confidence interval: 1.38 to 87.38) of having X4 tropic viruses than those with non-HHE. After adjusting for antiretroviral (ARV) therapy, neither the presence of HHE nor the use of ARV was associated with X4 tropic viruses. Our results suggest that CCR5 HHE and ARV treatment might be associated with the presence of HIV-1 X4 tropic viruses.

  13. Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5

    Science.gov (United States)

    Sorce, S; Bonnefont, J; Julien, S; Marq-Lin, N; Rodriguez, I; Dubois-Dauphin, M; Krause, KH

    2010-01-01

    Background and purpose: The chemokine receptor CCR5 is well known for its function in immune cells; however, it is also expressed in the brain, where its specific role remains to be elucidated. Because genetic factors may influence the risk of developing cerebral ischaemia or affect its clinical outcome, we have analysed the role of CCR5 in experimental stroke. Experimental approach: Permanent cerebral ischaemia was performed by occlusion of the middle cerebral artery in wild-type and CCR5-deficient mice. Locomotor behaviour, infarct size and histochemical alterations were analysed at different time points after occlusion. Key results: The cerebral vasculature was comparable in wild-type and CCR5-deficient mice. However, the size of the infarct and the motor deficits after occlusion were markedly increased in CCR5-deficient mice as compared with wild type. No differences between wild-type and CCR5-deficient mice were elicited by occlusion with respect to the morphology and abundance of astrocytes and microglia. Seven days after occlusion the majority of CCR5-deficient mice displayed neutrophil invasion in the infarct region, which was not observed in wild type. As compared with wild type, the infarct regions of CCR5-deficient mice were characterized by increased neuronal death. Conclusions and implications: Lack of CCR5 increased the severity of brain injury following occlusion of the middle cerebral artery. This is of particular interest with respect to the relatively frequent occurrence of CCR5 deficiency in the human population (1–2% of the Caucasian population) and the advent of CCR5 inhibitors as novel drugs. PMID:20423342

  14. Detecting Terrorism Incidence Type from News Summary

    DEFF Research Database (Denmark)

    Nizamani, Sarwat; Memon, Nasrullah

    2012-01-01

    The paper presents the experiments to detect terrorism incidence type from news summary data. We have applied classification techniques on news summary data to analyze the incidence and detect the type of incidence. A number of experiments are conducted using various classification algorithms...... and results show that a simple decision tree classifier can learn incidence type with satisfactory results from news data....

  15. Making the News: Jobs in TV Journalism

    Science.gov (United States)

    Csorny, Lauren

    2009-01-01

    What do TV news workers do each day? For many of them, contributing to daily news broadcasts has changed greatly over the years. This evolution will likely continue for years to come. And more changes to news production are expected, according to Tom Weir, an associate professor at the University of South Carolina's School of Journalism and Mass…

  16. Daily Market News Sentiment and Stock Prices

    NARCIS (Netherlands)

    D.E. Allen (David); M.J. McAleer (Michael); A.K. Singh (Abhay)

    2015-01-01

    textabstractIn recent years there has been a tremendous growth in the influx of news related to traded assets in international financial markets. This financial news is now available via print media but also through real-time online sources such as internet news and social media sources. The

  17. Technology: News Readers and Other Handy Utilities

    Science.gov (United States)

    Van Horn, Royal

    2004-01-01

    In this article, the author discusses how there are advantages and disadvantages to using an Internet News Reader instead of a Web browser. The major advantage is that one can read the headlines and short summaries of news articles from dozens of sources quickly. Another advantage the author points out to news readers is that one gets a short…

  18. Perceptions of Advertising Influence on Broadcast News.

    Science.gov (United States)

    Brown, Hubert W.; Barnes, Beth E.

    2001-01-01

    Finds that while students (studying broadcast journalism or advertising) and practitioners (station news directors and agency media directors) were in agreement on the majority of opinion statements discussing advertising's influence on broadcast news content, except students were less bothered by advertising's influence on news content than were…

  19. News Resources on the World Wide Web.

    Science.gov (United States)

    Notess, Greg R.

    1996-01-01

    Describes up-to-date news sources that are presently available on the Internet and World Wide Web. Highlights include electronic newspapers; AP (Associated Press) sources and Reuters; sports news; stock market information; New York Times; multimedia capabilities, including CNN Interactive; and local and regional news. (LRW)

  20. Cankao Xiaoxi: News for China's Cadre.

    Science.gov (United States)

    Atwood, L. Erwin; Lin, N.

    1982-01-01

    Reports that middle-level Chinese government officials are given almost verbatim translations of selected news stories and commentary from around the world in a publication called "News for Reference," which is widely distributed in China by the Hsinhua news agency. (FL)

  1. Visualizing news: obstacles, challenges, and solutions

    NARCIS (Netherlands)

    Dr. Piet Bakker; Gerard Smit; Yael de Haan; Laura Buijs

    2013-01-01

    Depicting news graphically is considered an apt way to deal with challenges of modern journalism: to disclose big data, and present news attractively, visually, and fast to grasp. This study delves into reported obstacles and challenges for the production of news visualizations. It focuses on the

  2. How to Tell Bad News

    Science.gov (United States)

    Long, Nicholas J.

    2012-01-01

    Therapists, physicians, police officers, and emergency staff often are the messengers of bad news. They have to tell a patient, a parent, or a loved one about a death, an accident, a school shooting, a life-threatening diagnosis, a terrorist attack, or a suicide. Usually the messenger bears a heavy responsibility but has little training and seeks…

  3. The Dutch and the news

    NARCIS (Netherlands)

    Annemarie Wennekers; Jos de Haan

    2017-01-01

    Original title: Nederlanders en nieuws For a long time, the television and newspapers were the most prominent news sources in the Netherlands, but digitalisation and the rise of new media have caused major shifts in the media landscape. Based on a time use survey focusing on media (Media:Tijd

  4. Journalism and Explaining News Content

    NARCIS (Netherlands)

    Albæk, E.; Skovsgaard, M.; de Vreese, C.H.; Nussbaum, J.F.

    Three models are presented to explain variation in news content. In the first model the explanation is based on the individual journalist, in the second model on the professional journalist, and in the third model on the organized journalist. The individual journalist model focuses on how the

  5. Myth, Method and International News.

    Science.gov (United States)

    Lule, Jack

    Defining myth as a cultural narrative in symbolic form that articulates a world view and offers consensus with that view, this paper uses a brief "New York Times" report on the Soviet shooting down of South Korean airline flight 007 as the basis for comparison of international news and myth. Following a review of the literature on myth…

  6. Zimbabwe Science News: Editorial Policies

    African Journals Online (AJOL)

    Focus and Scope. The Zimbabwe Scientific Association was founded in Bulawayo in 1899 to promote the study and advancement of science in Zimbabwe and to facilitate the acquisition and dissemination of scientific knowledge. The Zimbabwe Science News was first published in 1967 and is now in its thirty-third volume.

  7. Norepinephrine inhibits macrophage migration by decreasing CCR2 expression.

    Directory of Open Access Journals (Sweden)

    Fangming Xiu

    Full Text Available Increased incidences of infectious and septic complications during post-burn courses represent the main contributor to burn injury mortality. Sustained increases in catecholamine levels, especially norepinephrine (NE, contribute to immune disturbances in severely burned patients. The precise mechanisms underlying NE-mediated immunoregulation are not fully understood. Here we hypothesize that persistently elevated NE levels are associated with immunodysfunctions. We examined the effects of NE on the phenotype and functions of bone marrow-derived macrophages (BMMs. Whole mouse bone marrow cells were treated in vitro with 40 ng/mL of M-CSF and with 1 x 10(-6 M or 1 x 10(-8 M of NE or without NE for 7 days; cells were collected and stained with antibodies for CD11b, F4/80, MHC II and the inflammatory CC chemokine receptor 2 (CCR2. We found 1 x 10(-6 M of NE inhibited MHC II and CCR2 expression on CD11b(+/F4/80(+ BMM cells. It also inhibited BMM proliferation by inhibiting CSF-1R expression. On the contrary, 1 x 10(-8 M of NE slightly increased both MHC II and CCR2 expression on CD11b(+/F4/80(+ BMM cells but inhibited CD11b(+/F4/80(+ BMM proliferation. MCP-1 based migration assay showed that the migration of 1 x 10(-6 M of NE-treated BMM toward MCP-1 was significantly decreased compared to BMM without NE treatment. Both 1 x 10(-8 M and 1 x 10(-6 M of NE enhanced TNF-α production and phagocytosis of FITC-Dextran. Intracellular staining of transcriptional factor MafB showed that 1 x 10(-6 M of NE treatment enhanced its expression, whereas 1 x 10(-8 M of NE decreased expression. Stimulation with LPS in the last 24-hours of BMM culture further decreased CCR2 and MHC II expression of these BMM, suggesting the synergistic effect of LPS and NE on macrophage. Our results demonstrate that NE regulates macrophage differentiation, proliferation and function, and may play a critical role in the dysfunctional immune response post-burn.

  8. Fake news propagate differently from real news even at early stages of spreading

    OpenAIRE

    Zhao, Zilong; Zhao, Jichang; Sano, Yukie; Levy, Orr; Takayasu, Hideki; Takayasu, Misako; Li, Daqing; Havlin, Shlomo

    2018-01-01

    Social media can be a double-edged sword for modern communications, either a convenient channel exchanging ideas or an unexpected conduit circulating fake news through a large population. Existing studies of fake news focus on efforts on theoretical modelling of propagation or identification methods based on black-box machine learning, neglecting the possibility of identifying fake news using only structural features of propagation of fake news compared to those of real news and in particular...

  9. NEWS: Post-16 update

    Science.gov (United States)

    1999-05-01

    (post16) Making physics connect Doesn't Melvyn Bragg do a wonderful job, engaging both scientists and artists in sensitive discussion on Radio 4 about their methods and their purposes? But every week teachers have the chance to show their students that physics is a way of seeing the world that is well-connected with other aspects of knowledge and culture. The stakes are high: students who fail to appreciate this generally choose not to study the subject beyond GCSE. Most students find our preoccupation with technical detail off-putting. Accepting that we have a syllabus to cover, it's still a question of balance. In our teaching we should aim for variety in order to find ways to connect with every student's interests. Also, we can show that we (the nearest embodiment of a physicist some students will experience) are multidimensional and so fully human. Most important, teachers need flexibility to both encourage and respond to student comment and questions. The first booklet in the discussion series Shaping the Future takes up these themes. Rich in ideas for both immediate use and the longer term, it aims to stimulate debate and improve teaching. Copies cost £5.50 including postage and are available from Ingrid Ebeyer, Post-16 Initiative, Institute of Physics, 76 Portland Place, London W1N 3DH. How far is it? This question is asked in many family cars and school minibuses at the start of a journey, and answered by most in terms of hours and minutes rather than miles. What a good idea for introducing a social and historical perspective to a lesson on distance, velocity and time. How far can you actually get in a day? What is the range of human activity? Walking for eight hours will get many people about 25 miles. A pack horse will progress at much the same rate, but fast riding or a coach and team of horses will get further. Motorway driving (when the cones are on holiday) would take you nearly 500 miles. The 05.15 am train from Penzance arrives in Inverness at 7

  10. News from the Library: Stay connected and informed, try Mendeley!

    CERN Multimedia

    CERN Library

    2012-01-01

    Mendeley is a free bibliographic reference manager and academic social network. This online platform enables researchers to discover scientific publications and to collaborate with others online.   Mendeley helps you to organize the papers you read, share them with colleagues, and create bibliographies and reference lists. These papers can be accessed anywhere and on any electronic device. Mendeley currently has over 1.7 million active users in the world. It contains, therefore, a large crowd-sourced information library, with over 242 million documents. Recently, the software has opened up new pathways for collaboration and interaction between individual students and researchers and their institutions' libraries. The fee-based institutional edition of Mendeley not only allows access to the Library's online resources, but also facilitates communication and collaboration within your group on the platform. The CERN Library has now opened a free trial to the Me...

  11. Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications

    Science.gov (United States)

    Xu, Guoyan G.; Guo, Jia; Wu, Yuntao

    2015-01-01

    The human immunodeficiency virus (HIV) causes acquired immumodeficiency syndrome (AIDS), one of the worst global pandemic. The virus infects human CD4 T cells and macrophages, and causes CD4 depletion. HIV enters target cells through the binding of the viral envelope glycoprotein to CD4 and the chemokine coreceptor, CXCR4 or CCR5. In particular, the CCR5-utilizing viruses predominate in the blood during the disease course. CCR5 is expressed on the surface of various immune cells including macrophages, monocytes, microglia, dendric cells, and active memory CD4 T cells. In the human population, the CCR5 genomic mutation, CCR5Δ32, is associated with relative resistance to HIV. These findings paved the way for the discovery and development of CCR5 inhibitors to block HIV transmission and replication. Maraviroc, discovered as a CCR5 antagonist, is the only CCR5 inhibitor that has been approved by both US FDA and the European Medicines Agency (EMA) for treating HIV/AIDS patients. In this review, we summarize the medicinal chemistry and clinical studies of Maraviroc. PMID:25159165

  12. Profile of State College and Career Readiness Assessments (CCR) Policy. Florida

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Florida's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  13. Profile of State College and Career Readiness Assessments (CCR) Policy. Arkansas

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Arkansas' college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  14. Profile of State College and Career Readiness Assessments (CCR) Policy. Minnesota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Minnesota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  15. Profile of State College and Career Readiness Assessments (CCR) Policy. Alaska

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alaska's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  16. Profile of State College and Career Readiness Assessments (CCR) Policy. South Carolina

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on South Carolina's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  17. 77 FR 57566 - Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review...

    Science.gov (United States)

    2012-09-18

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OW-2012-0035; FRL-9730-7] Announcement of Public Meeting on the Consumer Confidence Report (CCR) Rule Retrospective Review and Request for Public Comment on Potential Approaches to Electronic Delivery of the CCR; Correction AGENCY: Environmental Protection Agency...

  18. Profile of State College and Career Readiness Assessments (CCR) Policy. Kentucky

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Kentucky's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  19. Profile of State College and Career Readiness Assessments (CCR) Policy. Georgia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Georgia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  20. Profile of State College and Career Readiness Assessments (CCR) Policy. North Dakota

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on North Dakota's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  1. Profile of State College and Career Readiness Assessments (CCR) Policy. Alabama

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Alabama's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  2. Profile of State College and Career Readiness Assessments (CCR) Policy. New Mexico

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on New Mexico's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  3. Profile of State College and Career Readiness Assessments (CCR) Policy. Tennessee

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on Tennessee's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  4. Profile of State College and Career Readiness Assessments (CCR) Policy. California

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on California's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  5. Profile of State College and Career Readiness Assessments (CCR) Policy. West Virginia

    Science.gov (United States)

    Center on Education Policy, 2011

    2011-01-01

    This individual profile provides information on West Virginia's college and career readiness assessment policy. Some of the categories presented include: (1) CCR assessment policy; (2) Purpose; (3) Major changes in CCR assessment policy since the 2009-10 school year for financial reasons; (4) State financial support for students to take the CCR…

  6. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

    Directory of Open Access Journals (Sweden)

    Qingwen Jin

    Full Text Available Insertion of T4 lysozyme (T4L into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed.We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects.Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1 infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5.Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

  7. The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

    Science.gov (United States)

    Jin, Qingwen; Chen, Hong; Wang, Xingxia; Zhao, Liandong; Xu, Qingchen; Wang, Huijuan; Li, Guanyu; Yang, Xiaofan; Ma, Hongming; Wu, Haoquan; Ji, Xiaohui

    2015-01-01

    Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed. We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects. Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5. Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.

  8. CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV.

    Science.gov (United States)

    Kim, Michelle B; Giesler, Kyle E; Tahirovic, Yesim A; Truax, Valarie M; Liotta, Dennis C; Wilson, Lawrence J

    2016-12-01

    The chemokine receptor CCR5 has garnered significant attention in recent years as a target to treat HIV infection largely due to the approval and success of the drug Maraviroc. The side effects and inefficiencies with other first generation agents led to failed clinical trials, prompting the development of newer CCR5 antagonists. Areas covered: This review aims to survey the current status of 'next generation' CCR5 antagonists in the preclinical pipeline with an emphasis on emerging agents for the treatment of HIV infection. These efforts have culminated in the identification of advanced second-generation agents to reach the clinic and the dual CCR5/CCR2 antagonist Cenicriviroc as the most advanced currently in phase II clinical studies. Expert opinion: The clinical success of CCR5 inhibitors for treatment of HIV infection has rested largely on studies of Maraviroc and a second-generation dual CCR5/CCR2 antagonist Cenicriviroc. Although research efforts identified several promising preclinical candidates, these were dropped during early clinical studies. Despite patient access to Maraviroc, there is insufficient enthusiasm surrounding its use as front-line therapy for treatment of HIV. The non-HIV infection related development activities for Maraviroc and Cenicriviroc may help drive future interests.

  9. Elucidation of the CCR1- and CCR5-binding modes of MIP-1α by application of an NMR spectra reconstruction method to the transferred cross-saturation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Yoshiura, Chie; Ueda, Takumi; Kofuku, Yutaka; Matsumoto, Masahiko; Okude, Junya; Kondo, Keita; Shiraishi, Yutaro; Shimada, Ichio, E-mail: shimada@iw-nmr.f.u-tokyo.ac.jp [The University of Tokyo, Graduate School of Pharmaceutical Sciences (Japan)

    2015-12-15

    C–C chemokine receptor 1 (CCR1) and CCR5 are involved in various inflammation and immune responses, and regulate the progression of the autoimmune diseases differently. However, the number of residues identified at the binding interface was not sufficient to clarify the differences in the CCR1- and CCR5-binding modes to MIP-1α, because the NMR measurement time for CCR1 and CCR5 samples was limited to 24 h, due to their low stability. Here we applied a recently developed NMR spectra reconstruction method, Conservation of experimental data in ANAlysis of FOuRier, to the amide-directed transferred cross-saturation experiments of chemokine receptors, CCR1 and CCR5, embedded in lipid bilayers of the reconstituted high density lipoprotein, and MIP-1α. Our experiments revealed that the residues on the N-loop and β-sheets of MIP-1α are close to both CCR1 and CCR5, and those in the C-terminal helix region are close to CCR5. These results suggest that the genetic influence of the single nucleotide polymorphisms of MIP-1α that accompany substitution of residues in the C-terminal helix region, E57 and V63, would provide clues toward elucidating how the CCR5–MIP-1α interaction affects the progress of autoimmune diseases.

  10. Limited protective effect of the CCR5Δ32/CCR5Δ32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K. N.; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)–infected patients with hemophilia. One patient (0.6%) had the CCR5Δ32/CCR5Δ32 genotype (which occurs in ∼2% of the Scandinavian population...

  11. News of the world

    International Nuclear Information System (INIS)

    Anon.

    2013-01-01

    This document gathers information from nuclear industry throughout the world. The most relevant follows. The reactor 1 of the Kudankulam site has diverged and is expected to be connected to the grid soon. This reactor is a VVER-1000 reactor whose power output will reach 1000 MW, it is the most powerful of the 21 reactors operating in India. China and Pakistan have signed an agreement for the construction of 2 reactors ACP-1000 near Karachi for a cost of 9.6 billion dollars. Ukraine and Japan have launched a common project whose purpose is the satellite-based monitoring of damaged nuclear plants Chernobyl and Fukushima. 4 countries of central Europe (Hungary, Poland, Czech Republic and Slovakia) have created a common center for the research and development of reactors of 4. generation. The European Commission has decided to grant a loan for the construction of the Pallas high flux multi-purpose reactor on the Petten site (The Netherlands). It will replace the High Flux reactor as soon as 2023 particularly for the production of radio-isotopes. Jordan plans to build its first reactor, this reactor will be a 5 MW research reactor situated at Irbid in the promises of the Sciences and Technologies University. (A.C.)

  12. Semantic Analysis of FBI News Reports

    DEFF Research Database (Denmark)

    Nizamani, Sarwat; Memon, Nasrullah

    2012-01-01

    In this paper we present our work on semantic analysis of FBI News reports. In the paper we have considered the News which are of the immense significance for the analyst who want to analyze the News of specific area. With this definite analysis we are able to extract critical events or concepts...... described in News along with entities involved in the event. These entities include important actors of the event or concept, with location and temporal information. This information will help News analyzers to retrieve the information of interest efficiently....

  13. Navigating cross-media news use

    DEFF Research Database (Denmark)

    Swart, Joëlle; Peters, Chris; Broersma, Marcel

    2017-01-01

    and other information are clearly shifting. Finally, our results show that in a world with a wide range of possibilities to consume news for free, paying for news can be considered an act of civic engagement. We argue that perceived news use and users’ appreciation of news should be studied in relation...... distinctive cross-media repertoires, and what makes these compositions meaningful. This article analyzes the value of different platforms, genres and practices in everyday life by mapping patterns of cross-media news use. Combining Q methodology with think-aloud protocols and day-in-the-life-interviews, five...

  14. The dual CCR5 and CCR2 inhibitor cenicriviroc does not redistribute HIV into extracellular space: implications for plasma viral load and intracellular DNA decline.

    Science.gov (United States)

    Kramer, Victor G; Hassounah, Said; Colby-Germinario, Susan P; Oliveira, Maureen; Lefebvre, Eric; Mesplède, Thibault; Wainberg, Mark A

    2015-03-01

    Cenicriviroc is a potent antagonist of the chemokine coreceptors 5 and 2 (CCR5/CCR2) and blocks HIV-1 entry. The CCR5 inhibitor maraviroc has been shown in tissue culture to be able to repel cell-free virions from the cell surface into extracellular space. We hypothesized that cenicriviroc might exhibit a similar effect, and tested this using clinical samples from the Phase IIb study 652-2-202, by measuring rates of intracellular DNA decline. We also monitored viral RNA levels in culture fluids. We infected PM-1 cells with CCR5-tropic HIV-1 BaL in the presence or absence of inhibitory concentrations of cenicriviroc (20 nM) or maraviroc (50 nM) or controls. Viral load levels and p24 were measured by ELISA, quantitative PCR and quantitative real-time reverse transcription PCR at 4 h post-infection. Frozen PBMC DNA samples from 30 patients with virological success in the Phase IIb study were studied, as were early and late reverse transcript levels. Docking studies compared binding between cenicriviroc/CCR5 and maraviroc/CCR5. Unlike maraviroc, cenicriviroc did not cause an increase in the amount of virus present in culture fluids at 4 h compared with baseline. The use of cenicriviroc did, however, result in lower levels of intracellular viral DNA after 4 h. Structural modelling indicates that cenicriviroc binds more deeply than maraviroc to the hydrophobic pocket of CCR5, providing an explanation for the absence of viral rebound with cenicriviroc. In contrast to maraviroc, cenicriviroc does not repel virus back into extracellular space. Differences in results may be due to superior binding of cenicriviroc to CCR5 compared with maraviroc. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Analysis of CCR5 and SDF-1 genetic variants and HIV infection in Indian population.

    Science.gov (United States)

    Gupta, A; Padh, Harish

    2015-08-01

    HIV-1 infection and progression exhibits interindividual variation. The polymorphism in the chemokine receptors CCR5 and CXCR4, the principal coreceptors for HIV-1 and their ligands like SDF-1 have a profound effect in altering the HIV-1 disease progression rate. A single nucleotide polymorphism designated SDF1-3'UTR-801G-A has been associated with resistance to HIV-1 infection or delayed progression to AIDS. In this study, the SDF1-3'A polymorphism, CCR5∆32 polymorphism and CCR5 promoter polymorphism at positions 58934 G/T, 59029 G/A, 59353 T/C, 59356 C/T, 59402 A/G and 59653 C/T were analysed in Indian population. The polymorphisms in HIV-1 patients and healthy individuals were evaluated by conventional PCR, RFLP-PCR and direct sequencing techniques. The CCR5∆32 mutant allele was found to be almost absent in Indian population. The analysis of the CCR5-59356C/T polymorphism revealed a trend towards an association of the C allele with an increased risk of HIV-1 infection. The frequency of allele CCR5-59356C was higher in HIV-1 patients (100%) as compared to healthy control subjects (89%, P = 0.003). The correlation of SDF1-3'A and CCR5 promoter CCR5-58934G/T, CCR5-59029G/A, CCR5-59353T/C, CCR5-59402 A/G and CCR5-59653C/T polymorphisms and protection to HIV-1 infection and progression to AIDS was found to be nonsignificant. Nine haplotypes with more than 1% frequency were detected but were not significant in their protective role against HIV. Comparative analysis with global populations showed a noteworthy difference in CCR5 and SDF-1 polymorphisms' frequency distribution, indicating the ethnic variability of Indians. Although susceptibility to infections cannot be completely dependent on one or few genetic variants, it is important to remember that SDF-1 and CCR5 variants have been correlated globally with HIV-1 infection and disease progression. In the light of that, higher frequency of SDF-1 variants in the Indian population is noteworthy. © 2015 John

  16. Frequency of CCR5delta32 in Brazilian populations

    Directory of Open Access Journals (Sweden)

    A.E. Vargas

    2006-03-01

    Full Text Available A sample of 103 randomly chosen healthy individuals from Alegrete, RS, Brazil, was tested for the CCR5delta32 allele, which is known to influence susceptibility to HIV-1 infection. The CCR5delta32 allele was identified by PCR amplification using specific primers flanking the region of deletion, followed by electrophoresis on a 3% agarose gel. The data obtained were compared to those reported for other populations and interpreted in terms of Brazilian history. The individuals studied came from a highly admixed population. Most of them were identified as white (N = 59, while blacks and browns (mulattoes were N = 13 and N = 31, respectively. The observed frequencies, considering the white, black and brown samples (6.8, 3.8, and 6.4%, respectively, suggest an important European parental contribution, even in populations identified as black and brown. However, in Brazil as a whole, this allele shows gradients indicating a relatively good correlation with the classification based on skin color and other physical traits, used here to define major Brazilian population groups.

  17. Enriquecimento com calda do CCR para face de barragens

    Directory of Open Access Journals (Sweden)

    A. P. Wendler

    Full Text Available A construção de barragens de CCR prioriza a minimização de interferências, como a execução da face de montante, para garantia da produtividade. O estudo procurou avaliar as propriedades físicas do CCR enriquecido com calda, em substituição ao concreto convencional usualmente empregado na face, utilizando os mesmos materiais, central de concreto, mão de obra e equipamentos, empregados na construção da Usina Hidrelétrica Mauá. Para tanto foram feitos prismas experimentais de campo (com diferentes relações água/cimento e quantidades de calda e posterior extração de testemunhos, os quais foram submetidos a ensaios mecânicos e de permeabilidade. Os resultados mostraram que para relações água/cimento 0,74, o material resultante atendeu às especificações de projeto, para consumos de cimento notadamente menores (entre 70 e 85% do CCV.

  18. Amino- and Carboxyl-Terminal CCR5 Mutations in Brazilian HIV-1-Infected Women and Homology Model of p.L55Q CCR5 Mutant.

    Science.gov (United States)

    Costa, Giselle Calasans de Souza; Nunes, Marcio Roberto T; Jesus, Jaqueline Goes; Novaes, Thiago; Cardoso, Jedson Ferreira; Sousa Júnior, Edivaldo Costa; Santos, Edson de Souza; Galvão-Castro, Bernardo; Zanette, Dalila Luciola; Gonçalves, Marilda de Souza; Alcantara, Luiz Carlos Junior

    2015-07-01

    Genetic factors from an HIV-1 host can affect the rate of progression to AIDS and HIV infection. To investigate the frequency of mutations in the CCR5 gene, HIV-1 samples from infected women and uninfected individuals were selected for sequencing of the CCR5 gene regions encoding the N- and C-terminal protein domains. Physicochemical CCR5 modeling and potential protein domain analysis were performed in order to evaluate the impact of the mutations found in the properties and structure of CCR5. The p.L55Q mutation in the N-terminal protein domain was observed only in uninfected individuals, with an allelic frequency of 1.8%. Physicochemical analysis revealed that the p.L55Q mutation magnified the flexibility and accessibility profiles and the modeling of CCR5 structures showed resulting in a small deviation to the right, as well as a hydrophobic to hydrophilic property alteration. The p.L55Q mutation also resulted in a slight modification of the electrostatic load of this region. Additionally, three novel silent mutations were found at the C-terminal coding region among HIV-1-infected women. The results suggest that the p.L55Q mutation might alter CCR5 conformation. Further studies should be conducted to verify the role of this mutation in HIV-1 susceptibility.

  19. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...ted gp120-elicited signalingpathways. PubmedID 12960231 Title Macrophage activation through CCR

  20. Engaging and Disengaging with Political News

    DEFF Research Database (Denmark)

    Ørmen, Jacob; Linaa Jensen, Jakob

    level, we further investigate the differences between users that only consume political news and users that also talk about politics with others. And on the tertiary level, we identify the most widespread communicative practices (e.g. sharing content on social network sites, writing comments on blogs...... (most notably by Prior, 2007; Stromback, Djerf-Pierre, & Shehata, 2012) that this development also can lead to an increase in the number of people who utilize this enhanced media choice to skip news altogether. One area that merits special attention in this context is political news. Critical engagement...... cluster analysis of a survey of the adult Danish population (n = 1205). The typology encompasses archetypical ways user can consume (e.g. watching news on TV, reading news in print as well as digital versions, encountering news on social networks and in face-to-face situations) and discuss political news...

  1. Good news is bad news: Leverage cycles and sudden stops

    OpenAIRE

    Akinci, Ozge; Chahrour, Ryan

    2015-01-01

    We show that a model with imperfectly forecastable changes in future productivity and an occasionally binding collateral constraint can match a set of stylized facts about “sudden stop” events. “Good” news about future productivity raises leverage during times of expansion, increasing the probability that the constraint binds, and a sudden stop occurs, in future periods. The economy exhibits a boom period in the run-up to the sudden stop, with output, consumption, and investment all above tre...

  2. The functional antagonist Met-RANTES: a modified agonist that induces differential CCR5 trafficking.

    Science.gov (United States)

    Kiss, Debra L; Longden, James; Fechner, Gregory A; Avery, Vicky M

    2009-01-01

    CC chemokine receptor 5 (CCR5) is a pro-inflammatory chemokine receptor that is expressed on cells of the immune system, and specializes in cell migration in response to inflammation and tissue damage. Due to its key role in cell communication and migration, this receptor is involved in various inflammatory and autoimmune diseases, in addition to HIV infection. Met-RANTES is a modified CCR5 ligand that has previously been shown to antagonize CCR5 activation and function in response to its natural ligands in vitro. In vivo, Met-RANTES is able to reduce inflammation in models of induced inflammatory and autoimmune diseases. However, due to the fact that Met-RANTES is also capable of partial agonist activity regarding receptor signaling and internalization, it is clear that Met-RANTES does not function as a conventional receptor antagonist. To further elucidate the effect of Met-RANTES on CCR5, receptor trafficking was investigated in a CHO-CCR5-GFP cell line using the Opera confocal plate reader. The internalization response of CCR5 was quantified, and showed that Met-RANTES internalized CCR5 in a slower, less potent manner than the agonists CCL3 and CCL5. Fluorescent organelle labeling and live cell imaging showed CCL3 and CCL5 caused CCR5 to traffic through sorting endosomes, recycling endosomes and the Golgi apparatus. In contrast, Met-RANTES caused CCR5 to traffic through sorting endosomes and the Golgi apparatus in a manner that was independent of recycling endosomes. As receptor trafficking impacts on cell surface expression and the ability of the receptor to respond to more ligand, this information may indicate an alternative regulation of CCR5 by Met-RANTES that allows the modified ligand to reduce inflammation through stimulation of a pro-inflammatory receptor.

  3. CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug Users

    Science.gov (United States)

    Huik, Kristi; Avi, Radko; Carrillo, Andrew; Harper, Nathan; Pauskar, Merit; Sadam, Maarja; Karki, Tõnis; Krispin, Tõnu; Kongo, Ulvi-Kaire; Jermilova, Tatiana; Rüütel, Kristi; Talu, Ave; Abel-Ollo, Katri; Uusküla, Anneli; Ahuja, Sunil K.; He, Weijing; Lutsar, Irja

    2013-01-01

    Background Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia. Methods Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2–CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5. Results Compared to IDUs seronegative for both HCV and HIV (HCV−/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (Padjusted = 1.89×10−4 and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% andHIV- IDUs and HCV−/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype. Conclusions Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs. PMID:23936229

  4. Peace Journalism and the news production process

    Directory of Open Access Journals (Sweden)

    Burkhard Bläsi

    2004-07-01

    Full Text Available In recent years various models of „peace journalism“ or „constructive conflict coverage“ have been proposed. These models suggest alternative ways of conflict reporting in order to contribute to processes of de-escalation, peacebuilding and reconciliation instead of escalating, exaggerating or neglecting conflicts. However, these models will remain irrelevant for the practical work of journalists unless they are connected to the reality of today’s media. Therefore it is of great importance to also direct our attention to the news production process. At the same time, studying the factors that influence the production of journalistic reporting in times of conflict and war means learning about the actual preconditions for any effort of constructive conflict coverage. Based on qualitative expert interviews with German journalists, this paper presents a model of the production process of conflict coverage. According to this model, the production process can be described as a complex interaction of six factors: (1 structural aspects of the media, (2 conflict situation on-site, (3 personal features of the individual journalist, (4 the political climate, (5 lobbies, (6 the audience. After presenting the general model and the discussion of its limitations and possible benefits, the influence of the „political climate“ factor is explored in more detail and illustrated with the experience of German journalists in the aftermath of 9/11. The author argues that peace journalism can only attract the critical number of journalists needed for a noticeable change in conflict coverage, if there are realizable suggestions for how to meet the obstacles journalists face in their daily work. The model of influencing factors affecting conflict coverage could be a good starting point for this undertaking, as it enables us, on the one hand, to systematize and specify attempts to implement peace journalism and, on the other hand, to develop a more

  5. Molecular cloning, structure and expressional profiles of two novel single-exon genes (PoCCR6A and PoCCR6B) in the Japanese flounder (Paralichthys olivaceus).

    Science.gov (United States)

    Wang, Lei; Zhang, Yong-zhen; Xu, Wen-teng; Jia, Xiao-dong; Chen, Song-lin

    2016-05-01

    CCR6 is an important binding receptor of CCL20 and beta-defensins, and has multiple functions in the innate and acquired immune responses. In this study, we cloned the PoCCR6A and PoCCR6B genes of the Japanese flounder and studied the gene structure and expression patterns of these two genes in bacterial infection. The full-length PoCCR6A cDNA is 1415 bp and the open reading frame (ORF) is 1113 bp, encoding a 370-amino-acid peptide. The full-length PoCCR6B cDNA is 2193 bp and the ORF is 1029 bp, encoding a 363-amino-acid peptide. The structures of PoCCR6A and PoCCR6B indicate that they are single-exon genes. The predicted proteins encoded by PoCCR6A and PoCCR6B have the typical G-protein-coupled receptor (GPCR) family signature of seven transmembrane domains and several conserved structural features. A tissue distribution analysis showed that PoCCR6A is predominately expressed in the intestine, gill, and blood, and PoCCR6B in the gill, spleen, and liver. The expression patterns of the two chemokine receptors were analyzed during bacterial infection. In spleen and kidney, the expression of PoCCR6A was significantly upregulated at 24 h after infection, whereas the expression of PoCCR6B was steady at these time points. While in intestine, both of them were upregulated at 6 h-12 h after infection, and in gill the expression levels of them were upregulated at 24 h. The patterns of expression suggested that PoCCR6A and PoCCR6B play an important role in the immune response of the Japanese flounder, especially in the mucosal tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Networked Intermedia Agenda Setting: The Geography of a Hyperlinked Scandinavian News Ecology

    DEFF Research Database (Denmark)

    Sjøvaag, Helle; Stavelin, Eirik; Karlsson, Michael

    How does agenda setting work within the hyperlinked Scandinavian news ecology? This paper investigates intermedia agenda setting within and between the local, regional, national and supra-national levels in Sweden, Denmark and Norway; analyses the center/periphery dimensions of hyperlink connecti......How does agenda setting work within the hyperlinked Scandinavian news ecology? This paper investigates intermedia agenda setting within and between the local, regional, national and supra-national levels in Sweden, Denmark and Norway; analyses the center/periphery dimensions of hyperlink...... connections, and evaluates the extent of centralization of hyperlinked news agendas in the three countries. As hyperlinks are the backbone of the Internet, studying hyperlinking facilitates analyses of the relative connectedness of local, regional, national and international news agendas. The analysis...

  7. NEWS: Post-16 update

    Science.gov (United States)

    Campbell, Peter

    2000-07-01

    sometimes hard-to-come-by information, insightful and occasionally witty comment and illustration. The fifth booklet, published in April this year, rounds off the series so far. For those who have not yet seen them, here are the questions that the booklets have explored: Making Physics Connect (editor: Peter Campbell). How can physics courses connect better with the learner and with other human activities and areas of knowledge? Physics in Mathematical Mood (editor: Simon Carson). How can we teach physics in an appropriately mathematical way, conveying the beauty and power of mathematical reasoning to students? Physics in Vocational Courses (editor: Ken Gadd). In the new National Qualifications Framework, what role should physics play in the `general vocational' and `vocational' pathways? The Study of Matter (editor: Claire Davis). What aspects of a wide and interdisciplinary subject should be included in courses at advanced level, and how can these best be taught? Revitalising Physics Education (editor: Andrew Morris). What can we learn from histories of physics and of education, or from curriculum development projects of the last thirty years? What can be said about teaching and learning physics beyond qualifications, or learned from international developments in physics education? These booklets should find their way into every physics department in the UK. They will be of immediate practical use in schools or colleges, informing teaching while also providing stimulus material for discussion among physics teachers. (The latter would rightly be called in-service training.) Student teachers will find them a good guide covering new terrain. Lecturers at higher education level will gain valuable insight into changes affecting their undergraduate intake. And the physics advisory committee of every Awarding Body will surely want to discuss issues raised in the booklets. The main message overall is that, to meet tomorrow's challenges, the many parties involved in physics

  8. Misunderstanding International News in Brazil

    Directory of Open Access Journals (Sweden)

    Jacques Wainberg

    2006-06-01

    Full Text Available This study evaluates the nature of the Brazilian public comprehension of international news by revealing the quality of such reception with regard to a sample of 170 subjects randomly selected in the city of Porto Alegre, Brazil. A questionnaire was created taking as a basis the directives of Bloom et al(1972. Evaluated in it are the cognitive and aff ective dimensions of thought. In the fi rst case, questions were formulated that allowed the establishment of the level of knowledge of individuals, as well as their comprehension abilities, application, analysis, synthesis, and evaluation of a wide range of international news topics. For the aff ective dimension the following abilities were evaluated: attention, response, valorization, organization and the structuring of a value scale.

  9. Expression pattern of Ccr2 and Cx3cr1 in inherited retinal degeneration.

    Science.gov (United States)

    Kohno, Hideo; Koso, Hideto; Okano, Kiichiro; Sundermeier, Thomas R; Saito, Saburo; Watanabe, Sumiko; Tsuneoka, Hiroshi; Sakai, Tsutomu

    2015-10-12

    Though accumulating evidence suggests that microglia, resident macrophages in the retina, and bone marrow-derived macrophages can cause retinal inflammation which accelerates photoreceptor cell death, the details of how these cells are activated during retinal degeneration (RD) remain uncertain. Therefore, it is important to clarify which cells play a dominant role in fueling retinal inflammation. However, distinguishing between microglia and macrophages is difficult using conventional techniques such as cell markers (e.g., Iba-1). Recently, two mouse models for visualizing chemokine receptors were established, Cx3cr1 (GFP/GFP) and Ccr2 (RFP/RFP) mice. As Cx3cr1 is expressed in microglia and Ccr2 is reportedly expressed in activated macrophages, these mice have the potential to distinguish microglia and macrophages, yielding novel information about the activation of these inflammatory cells and their individual roles in retinal inflammation. In this study, c-mer proto-oncogene tyrosine kinase (Mertk) (-/-) mice, which show photoreceptor cell death due to defective retinal pigment epithelium phagocytosis, were employed as an animal model of RD. Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were established by breeding Mertk (-/-) , Cx3cr1 (GFP/GFP) , and Ccr2 (RFP/RFP) mice. The retinal morphology and pattern of inflammatory cell activation and invasion of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice were evaluated using retina and retinal pigment epithelium (RPE) flat mounts, retinal sections, and flow cytometry. Four-week-old Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice showed Cx3cr1-GFP-positive microglia in the inner retina. Cx3cr1-GFP and Ccr2-RFP dual positive activated microglia were observed in the outer retina and subretinal space of 6- and 8-week-old animals. Ccr2-RFP single positive bone marrow-derived macrophages were observed to migrate into the retina of Mertk (-/-) Cx3cr1 (GFP/+) Ccr2 (RFP/+) mice. These invading cells were still observed in the

  10. Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians

    Directory of Open Access Journals (Sweden)

    Gupta Arvind

    2007-04-01

    Full Text Available Abstract Background Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI. Transforming growth factor β1 (TGF β1 induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα, chemoattractant protein-1 (MCP-1, and regulated upon activation and normal T cell expressed and secreted (RANTES mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency. Methods Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR and 95% confidence intervals (CI. Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed. Results SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84. In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035. Conclusion Of the various cytokine gene

  11. NEWS: AAPT Summer Meeting

    Science.gov (United States)

    Mellema, Steve

    2000-11-01

    session concluded with the talk by this year's award winner for Excellence in Introductory College teaching, Dr Dwight Neuenschwander from Southern Nazarene University in Oklahoma. Dwight's talk, invoking both Charles Dickens' A Christmas Carol and Robert Pirsig's Zen and the Art of Motorcycle Maintenance, was memorable for clarifying both the connections and the differences between physics and physics teaching. At a second ceremonial session on Tuesday, Terrence Walker of The Ohio State University gave the Klopsteg Memorial Lecture, entitled The Big Bang: Seeing Back to the Beginning. This was followed by the presentation of the Robert A Millikan Award Lecture - Beauty in Physics and the Arts, by Thomas Rossing of Northern Illinois University. Over the years Tom has made many contributions to the teaching of the physics of sound and music, and his lecture made wonderful connections between physics and the arts. At the first plenary session on Monday, Dr Elaine Seymour, a sociologist from the University of Colorado, gave a talk entitled: We Know Science Majors Are Lost Because of Poor Teaching, But Why Do They Resist Our Efforts To Improve Their Learning Experience? She described students' responses and resistance to the implementation of active-learning methods. The talk was thought-provoking, particularly when so many other talks at this meeting described new attempts to incorporate such methods in different educational settings. At the second plenary session on Wednesday, Eric Poisson from the University of Guelph gave a very interesting talk about Gravitational Wave Astronomy and the LIGO and VIRGO projects, including their theoretical motivation and expected experimental results. On Tuesday evening there was a very special show of physics demonstrations by the `Third Eye' group from China. Their presentations embody a very interesting philosophy. Each demonstration is designed to illustrate one or more basic concepts in physics in a way that will be both memorable

  12. Asymmetric News Effects on Volatility: Good vs. Bad News in Good vs. Bad Times

    OpenAIRE

    Laakkonen, Helinä; Lanne, Markku

    2008-01-01

    We study the impact of positive and negative macroeconomic US and European news announcements in different phases of the business cycle on the highfrequency volatility of the EUR/USD exchange rate. The results suggest that in general bad news increases volatility more than good news. The news effects also depend on the state of the economy: bad news increases volatility more in good times than in bad times, while there is no difference between the volatility effects of good news in bad and go...

  13. Delivering bad news in emergency care medicine.

    Science.gov (United States)

    Maynard, Douglas W

    2017-01-01

    Forecasting is a strategy for delivering bad news and is compared to two other strategies, stalling and being blunt. Forecasting provides some warning that bad news is forthcoming without keeping the recipient in a state of indefinite suspense (stalling) or conveying the news abruptly (being blunt). Forecasting appears to be more effective than stalling or being blunt in helping a recipient to "realize" the bad news because it involves the deliverer and recipient in a particular social relation. The deliverer of bad news initiates the telling by giving an advance indication of the bad news to come; this allows the recipient to calculate the news in advance of its final presentation, when the deliverer confirms what the recipient has been led to anticipate. Thus, realization of bad news emerges from intimate collaboration, whereas stalling and being blunt require recipients to apprehend the news in a social vacuum. Exacerbating disruption to recipients' everyday world, stalling and being blunt increase the probability of misapprehension (denying, blaming, taking the situation as a joke, etc.) and thereby inhibit rather than facilitate realization. Particular attention is paid to the "perspective display sequence", a particular forecasting strategy that enables both confirming the recipient's perspective and using that perspective to affirm the clinical news. An example from acute or emergency medicine is examined at the close of the paper.

  14. The coreceptor mutation CCR5Δ32 influences the dynamics of HIV epidemics and is selected for by HIV

    OpenAIRE

    Sullivan, Amy D.; Wigginton, Janis; Kirschner, Denise

    2001-01-01

    We explore the impact of a host genetic factor on heterosexual HIV epidemics by using a deterministic mathematical model. A protective allele unequally distributed across populations is exemplified in our models by the 32-bp deletion in the host-cell chemokine receptor CCR5, CCR5Δ32. Individuals homozygous for CCR5Δ32 are protected against HIV infection whereas those heterozygous for CCR5Δ32 have lower pre-AIDS viral loads and delayed progression to AIDS. CCR5Δ32 may limit HIV spread by decre...

  15. CCR5 susceptibility to ligand-mediated down-modulation differs between human T lymphocytes and myeloid cells

    OpenAIRE

    Fox, James M.; Kasprowicz, Richard; Hartley, Oliver; Signoret, Nathalie

    2015-01-01

    CCR5 is a chemokine receptor expressed on leukocytes and a coreceptor used by HIV-1 to enter CD4+ T lymphocytes and macrophages. Stimulation of CCR5 by chemokines triggers internalization of chemokine-bound CCR5 molecules in a process called down-modulation, which contributes to the anti-HIV activity of chemokines. Recent studies have shown that CCR5 conformational heterogeneity influences chemokine-CCR5 interactions and HIV-1 entry in transfected cells or activated CD4+ T lymphocytes. Howeve...

  16. Effects of chemokine receptor signalling on cognition-like, emotion-like and sociability behaviours of CCR6 and CCR7 knockout mice.

    Science.gov (United States)

    Jaehne, E J; Baune, B T

    2014-03-15

    Inflammation is regarded as an important mechanism of neuropsychiatric disorders. Chemokines, which are a part of the immune system, have effects on various aspects of brain function, but little is known about their effects on behaviour. We have compared the cognition-like behaviour (learning and spatial memory) of CCR6(-/-) and CCR7(-/-) mice with wild type (WT) C57BL/6 mice, in the Barnes maze, as well as a range of other behaviours, including exploratory, anxiety and depression-like behaviour, using a battery of tests. Levels of cytokines TNF-α, IL-1β and IL-6 were also measured. In the Barnes maze, CCR7(-/-) mice were shown to take longer to learn the location of the escape box on the 1st of 4 days of training. In the behavioural battery, CCR6(-/-) mice showed higher locomotor activity and lower anxiety in the open field test, and a lack of preference for social novelty in a sociability test. CCR7(-/-) mice behaved much like WT mice, although showed higher anxiety in Elevated Zero Maze. While baseline saccharin preference in a 2-bottle choice test, a test for anhedonia depression-like behaviour, was equal in all strains at baseline, weekly tests showed that both CCR6(-/-) and CCR7(-/-) mice developed a decreased preference for saccharin compared to WT over time. There were no differences between strains in any of the cytokines measured. These results suggest that chemokine receptors may play a role in cognition and learning behaviour, as well as anxiety and other behaviours, although the biological mechanisms are still unclear. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. CCR5 down-regulates osteoclast function in orthodontic tooth movement.

    Science.gov (United States)

    Andrade, I; Taddei, S R A; Garlet, G P; Garlet, T P; Teixeira, A L; Silva, T A; Teixeira, M M

    2009-11-01

    During orthodontic tooth movement, there is local production of chemokines and an influx of leukocytes into the periodontium. CCL5 plays an important role in osteoclast recruitment and activation. This study aimed to investigate whether the CCR5-receptor influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and CCR5-deficient mice (CCR5(-/-)). The expression of mediators involved in bone remodeling was evaluated in periodontal tissues by Real-time PCR. The number of TRAP-positive osteoclasts and the expression of cathepsin K, RANKL, and MMP13 were significantly higher in CCR5(-/-). Meanwhile, the expression of two osteoblastic differentiation markers, RUNX2 and osteocalcin, and that of bone resorption regulators, IL-10 and OPG, were lower in CCR5(-/-). Analysis of the data also showed that CCR5(-/-) exhibited a greater amount of tooth movement after 7 days of mechanical loading. The results suggested that CCR5 might be a down-regulator of alveolar bone resorption during orthodontic movement.

  18. Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A

    2014-01-01

    The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13-21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics.

  19. Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy.

    Science.gov (United States)

    Wang, Charlene; Abdel-Mohsen, Mohamed; Strain, Matthew C; Lada, Steven M; Yukl, Steven; Cockerham, Leslie R; Pilcher, Christopher D; Hecht, Frederick M; Sinclair, Elizabeth; Liegler, Teri; Richman, Douglas D; Deeks, Steven G; Pillai, Satish K

    2014-12-01

    Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. For Video Games, Bad News Is Good News: News Reporting of Violent Video Game Studies.

    Science.gov (United States)

    Copenhaver, Allen; Mitrofan, Oana; Ferguson, Christopher J

    2017-12-01

    News coverage of video game violence studies has been critiqued for focusing mainly on studies supporting negative effects and failing to report studies that did not find evidence for such effects. These concerns were tested in a sample of 68 published studies using child and adolescent samples. Contrary to our hypotheses, study effect size was not a predictor of either newspaper coverage or publication in journals with a high-impact factor. However, a relationship between poorer study quality and newspaper coverage approached significance. High-impact journals were not found to publish studies with higher quality. Poorer quality studies, which tended to highlight negative findings, also received more citations in scholarly sources. Our findings suggest that negative effects of violent video games exposure in children and adolescents, rather than large effect size or high methodological quality, increase the likelihood of a study being cited in other academic publications and subsequently receiving news media coverage.

  1. The Black Death and AIDS: CCR5-Delta32 in genetics and history.

    Science.gov (United States)

    Cohn, S K; Weaver, L T

    2006-08-01

    Black Death and AIDS are global pandemics that have captured the popular imagination, both attracting extravagant hypotheses to account for their origins and geographical distributions. Medical scientists have recently attempted to connect these two great pandemics. Some argue that the Black Death of 1346-52 was responsible for a genetic shift that conferred a degree of resistance to HIV 1 infection, that this shift was almost unique to European descendents, and that it mirrors the intensity of Black Death mortality within Europe. Such a hypothesis is not supported by the historical evidence: the Black Death did not strike Europe alone but spread from the east, devastating regions such as China, North Africa, and the Middle East as much or even more than Europe. Further, in Europe its levels of mortality do not correspond with the geographic distribution of the proportion of descendents with this CCR5 gene. If anything, the gradient of Black Death mortality sloped in the opposite direction from that of present-day genotypes: the heaviest casualties were in the Mediterranean, the very regions whose descendents account for the lowest incidences of the HIV-1 resistant allele. We argue that closer collaboration between historians and scientists is needed to understand the selective pressures on genetic mutation, and the possible triggers for changes in genetic spatial frequencies over the past millennia. This requires care and respect for each other's methods of evaluating data.

  2. Control of Both Myeloid Cell Infiltration and Angiogenesis by CCR1 Promotes Liver Cancer Metastasis Development in Mice

    Directory of Open Access Journals (Sweden)

    Mathieu Paul Rodero

    2013-06-01

    Full Text Available Expression of the CC chemokine receptor 1 (CCR1 by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.

  3. Epigenetic control of Ccr7 expression in distinct lineages of lung dendritic cells.

    Science.gov (United States)

    Moran, Timothy P; Nakano, Hideki; Kondilis-Mangum, Hrisavgi D; Wade, Paul A; Cook, Donald N

    2014-11-15

    Adaptive immune responses to inhaled allergens are induced following CCR7-dependent migration of precursor of dendritic cell (pre-DC)-derived conventional DCs (cDCs) from the lung to regional lymph nodes. However, monocyte-derived (moDCs) in the lung express very low levels of Ccr7 and consequently do not migrate efficiently to LN. To investigate the molecular mechanisms that underlie this dichotomy, we studied epigenetic modifications at the Ccr7 locus of murine cDCs and moDCs. When expanded from bone marrow precursors, moDCs were enriched at the Ccr7 locus for trimethylation of histone 3 lysine 27 (H3K27me3), a modification associated with transcriptional repression. Similarly, moDCs prepared from the lung also displayed increased levels of H3K27me3 at the Ccr7 promoter compared with migratory cDCs from that organ. Analysis of DC progenitors revealed that epigenetic modification of Ccr7 does not occur early during DC lineage commitment because monocytes and pre-DCs both had low levels of Ccr7-associated H3K27me3. Rather, Ccr7 is gradually silenced during the differentiation of monocytes to moDCs. Thus, epigenetic modifications of the Ccr7 locus control the migration and therefore the function of DCs in vivo. These findings suggest that manipulating epigenetic mechanisms might be a novel approach to control DC migration and thereby improve DC-based vaccines and treat inflammatory diseases of the lung. Copyright © 2014 by The American Association of Immunologists, Inc.

  4. Involvement of CCR6/CCL20/IL-17 Axis in NSCLC Disease Progression

    Science.gov (United States)

    Amir, Gail; Demma, Jonathan; Vernea, Fiona; Beider, Katia; Shlomai, Zippora; Wald, Hanna; Zamir, Gideon; Shapira, Oz M.; Peled, Amnon; Wald, Ori

    2011-01-01

    Objectives Autocrine and paracrine chemokine/chemokine receptor-based interactions promote non-small-cell-lung-cancer (NSCLC) carcinogenesis. CCL20/CCR6 interactions are involved in prostatic and colonic malignancy pathogenesis. The expression and function of CCL20/CCR6 and its related Th-17 type immune response in NSCLC is not yet defined. We sought to characterize the role of the CCL20/CCR6/IL-17 axis in NSCLC tumor growth. Methods A specialized histopathologist blindly assessed CCL20/CCR6 expression levels in 49 tissue samples of NSCLC patients operated in our department. Results were correlated to disease progression. Colony assays, ERK signaling and chemokine production were measured to assess cancer cell responsiveness to CCL20 and IL-17 stimulation. Results CCL20 was highly expressed in the majority (38/49, 77.5%) of tumor samples. Only a minority of samples (8/49, 16.5%) showed high CCR6 expression. High CCR6 expression was associated with a shorter disease-free survival (P = 0.008) and conferred a disease stage-independent 4.87-fold increased risk for disease recurrence (P = 0.0076, CI 95% 1.52–15.563). Cancerous cell colony-forming capacity was increased by CCL20 stimulation; this effect was dependent in part on ERK phosphorylation and signaling. IL-17 expression was detected in NSCLC; IL-17 potentiated the production of CCL20 by cancerous cells. Conclusion Our findings suggest that the CCL20/CCR6 axis promotes NSCLC disease progression. CCR6 is identified as a potential new prognostic marker and the CCL20/CCR6/IL-17 axis as a potential new therapeutic target. Larger scale studies are required to consolidate these observations. PMID:21949768

  5. DISTRIBUTION OF CCR2-64I GENE AMONG THE TRIBES AND CASTE POPULATION OF VIDARBHA, INDIA.

    Directory of Open Access Journals (Sweden)

    Arvind B Chavhan

    2013-08-01

    Results: The genotyping for the CCR2-64I mutation among the selected tribe and a caste reveal that all of the tribes and a caste was found to be heterozygous for the CCR2-64I mutation. Among the tribes Gonds showed highest genotype frequency (29.28% and (11.76% for heterozygous (CCR2/64I and Homozygous (64I/64I respectively, having an allelic frequency (0.233. A pooled allelic frequencies of the wild-type allele CCR2 and CCR2 64I the variant were found to be 0.854 and 0.146, respectively. No significant deviations from the HWE were observed for tribes and a caste population for the CCR2- 64I mutant χ2=2.76. The study reports the presence of mutant CCR2- 64I gene in tribes and caste population from Vidarbha region.

  6. Quantum continual measurements and a posteriori collapse on CCR

    International Nuclear Information System (INIS)

    Belavkin, V.P.

    1992-01-01

    A quantum stochastic model for the Markovian dynamics of an open system under the nondemolition unsharp observation which is continuous in time, is given. A stochastic equation for the posterior evolution of a quantum continuously observed system is derived and the spontaneous collapse (stochastically continuous reduction of the wave packet) is described. The quantum Langevin evolution equation is solved for the case of a quasi-free Hamiltonian in the initial CCR algebra with a linear output channel, and the posterior dynamics corresponding to an initial Gaussian state is found. It is shown for an example of the posterior dynamics of a quantum oscillator that any mixed state under a complete nondemolition measurement collapses exponentially to a pure Gaussian one. (orig.)

  7. Internalization of the chemokine receptor CCR4 can be evoked by orthosteric and allosteric receptor antagonists

    OpenAIRE

    Ajram, Laura; Begg, Malcolm; Slack, Robert; Cryan, Jenni; Hall, David; Hodgson, Simon; Ford, Alison; Barnes, Ashley; Swieboda, Dawid; Mousnier, Aurelie; Solari, Roberto

    2014-01-01

    The chemokine receptor CCR4 has at least two natural agonist ligands, MDC (CCL22) and TARC (CCL17) which bind to the same orthosteric site with a similar affinity. Both ligands are known to evoke chemotaxis of CCR4-bearing T cells and also elicit CCR4 receptor internalization. A series of small molecule allosteric antagonists have been described which displace the agonist ligand, and inhibit chemotaxis. The aim of this study was to determine which cellular coupling pathways are involved in in...

  8. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo

    DEFF Research Database (Denmark)

    Motley, Michael P; Madsen, Daniel H; Jürgensen, Henrik J

    2016-01-01

    cellular endocytosis and lysosomal targeting, revealing a novel intracellular pathway for extravascular fibrin degradation. A C-C chemokine receptor type 2 (CCR2)-positive macrophage subpopulation constituted the majority of fibrin-uptaking cells. Consequently, cellular fibrin uptake was diminished...... by elimination of CCR2-expressing cells. The CCR2-positive macrophage subtype was different from collagen-internalizing M2-like macrophages. Cellular fibrin uptake was strictly dependent on plasminogen and plasminogen activator. Surprisingly, however, fibrin endocytosis was unimpeded by the absence of the fibrin...

  9. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  10. Synergistic combinations of the CCR5 inhibitor VCH-286 with other classes of HIV-1 inhibitors.

    Science.gov (United States)

    Asin-Milan, Odalis; Sylla, Mohamed; El-Far, Mohamed; Belanger-Jasmin, Geneviève; Haidara, Alpha; Blackburn, Julie; Chamberland, Annie; Tremblay, Cécile L

    2014-12-01

    Here, we evaluated the in vitro anti-HIV-1 activity of the experimental CCR5 inhibitor VCH-286 as a single agent or in combination with various classes of HIV-1 inhibitors. Although VCH-286 used alone had highly inhibitory activity, paired combinations with different drug classes led to synergistic or additive interactions. However, combinations with other CCR5 inhibitors led to effects ranging from synergy to antagonism. We suggest that caution should be exercised when combining CCR5 inhibitors in vivo. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. CD4-independent use of the CCR5 receptor by sequential primary SIVsm isolates

    Directory of Open Access Journals (Sweden)

    Thorstensson Rigmor

    2007-07-01

    Full Text Available Abstract Background CD4-independence has been taken as a sign of a more open envelope structure that is more accessible to neutralizing antibodies and may confer altered cell tropism. In the present study, we analyzed SIVsm isolates for CD4-independent use of CCR5, mode of CCR5-use and macrophage tropism. The isolates have been collected sequentially from 13 experimentally infected cynomolgus macaques and have previously been shown to use CCR5 together with CD4. Furthermore, viruses obtained early after infection were neutralization sensitive, while neutralization resistance appeared already three months after infection in monkeys with progressive immunodeficiency. Results Depending whether isolated early or late in infection, two phenotypes of CD4-independent use of CCR5 could be observed. The inoculum virus (SIVsm isolate SMM-3 and reisolates obtained early in infection often showed a pronounced CD4-independence since virus production and/or syncytia induction could be detected directly in NP-2 cells expressing CCR5 but not CD4 (CD4-independent-HIGH. Conversely, late isolates were often more CD4-dependent in that productive infection in NP-2/CCR5 cells was in most cases weak and was revealed only after cocultivation of infected NP-2/CCR5 cells with peripheral blood mononuclear cells (CD4-independent-LOW. Considering neutralization sensitivity of these isolates, newly infected macaques often harbored virus populations with a CD4-independent-HIGH and neutralization sensitive phenotype that changed to a CD4-independent-LOW and neutralization resistant virus population in the course of infection. Phenotype changes occurred faster in progressor than long-term non-progressor macaques. The phenotypes were not reflected by macrophage tropism, since all isolates replicated efficiently in macrophages. Infection of cells expressing CCR5/CXCR4 chimeric receptors revealed that SIVsm used the CCR5 receptor in a different mode than HIV-1. Conclusion Our

  12. News and Announcements

    Science.gov (United States)

    1999-04-01

    Classroom Activities Mean Teamwork As much as any other facet of the editing and production of the Journal, the Classroom Activity series means teamwork! The aim is for activities to be interesting and accessible to introductory students, based on inexpensive and readily available materials, connected by content to some part of the Journal issue, able to be integrated into the high school curriculum, and safe. There need to be questions posed and answers at the ready. Additional information in print and on the Web needs to be identified and checked. The activities are designed to be ready for teachers to hand to students, so they really need to work-that means that they go through a lot of testing in Journal House where there is, quite fittingly, no lab. This is a tall order, one requiring someone with experience in high school teaching. From the start of the Activities in September 1997, Nancy Gettys has had a major role in their success. While Nancy's primary responsibility is as the Technical Editor of JCE Software, she has experience in teaching high school and has called on that experience to try and test, expand, try again, plan the illustrations (remember the photographs of the activities with surface phenomena that were featured in the table of contents of the February 1998 issue?), and perhaps hardest of all-tell us when something will just not work in high school. Nancy continues to work with the Classroom Activities, but she now has a colleague in fellow high school teacher Erica Jacobsen who has recently joined our staff. Introducing... Erica Jacobsen joined our staff last fall as an editorial assistant and has recently become an assistant editor. She received her undergraduate degree in education from the University of Wisconsin-Madison. Her teaching licenses include certifications in chemistry, physics, biology, and natural science for grades six through twelve. During her undergraduate years, she worked with the Chemical Education Group. Her

  13. News with an attitude: assessing the mechanisms underlying the effects of opinionated news

    NARCIS (Netherlands)

    Boukes, M.; Boomgaarden, H.G.; Moorman, M.; de Vreese, C.H.

    2014-01-01

    Opinionated news targets communities of likeminded viewers, relies on dramaturgical storytelling techniques, and shares characteristics with political satire. Accordingly, opinionated news should be understood as a specific form of political entertainment. We have investigated the mechanisms

  14. Staphylococcus aureus Leukocidin LukED and HIV-1 gp120 Target Different Sequence Determinants on CCR5.

    Science.gov (United States)

    Tam, Kayan; Schultz, Megan; Reyes-Robles, Tamara; Vanwalscappel, Bénédicte; Horton, Joshua; Alonzo, Francis; Wu, Beili; Landau, Nathaniel R; Torres, Victor J

    2016-12-13

    Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry. These analyses showed that the second and third extracellular loops (ECL) of CCR5 are necessary and sufficient for LukED to target the receptor and promote cell lysis. In contrast, the second ECL of CCR5 is necessary but not sufficient for HIV-1 infectivity. The analysis of CCR5 point mutations showed that glycine-163 is critical for HIV-1 infectivity, while arginine-274 and aspartic acid-276 are critical for LukED cytotoxicity. Point mutations in ECL2 diminished both HIV-1 infectivity and LukED cytotoxicity. Treatment of cells with LukED did not interfere with CCR5-tropic HIV-1 infectivity, demonstrating that LukED and the viral envelope glycoprotein use nonoverlapping sites on CCR5. Analysis of point mutations in LukE showed that amino acids 64 to 69 in the rim domain are required for CCR5 targeting and cytotoxicity. Taking the results together, this study identified the molecular basis by which LukED targets CCR5, highlighting the divergent molecular interactions evolved by HIV-1 and LukED to interact with CCR5. The bicomponent pore-forming toxins are thought to play a vital role in the success of Staphylococcus aureus as a mammalian pathogen. One of the leukocidins, LukED, is necessary and sufficient for lethality in mice. At the molecular level, LukED causes cell lysis through binding to specific cellular receptors. CCR5 is one of the receptors targeted by LukED and is the major coreceptor for CCR5-tropic HIV-1. While the

  15. How to Write News for Broadcast and Print Media.

    Science.gov (United States)

    Dary, David

    This book is a primer on the techniques of news writing and the application of those principles to print and broadcast journalism. Chapters include: "The News Media," which presents a brief history of journalism and the foundations on which it is based; "What Is News?"; "Gathering News," which discusses news beats, reporters' qualifications, and…

  16. Annulus fibrosus cells express and utilize C-C chemokine receptor 5 (CCR5) for migration.

    Science.gov (United States)

    Liu, Weijun; Liu, David; Zheng, Justin; Shi, Peng; Chou, Po-Hsin; Oh, Chundo; Chen, Di; An, Howard S; Chee, Ana

    2017-05-01

    Disc degeneration is associated with the progressive loss of the proteoglycan content of the intervertebral disc, decreased matrix synthesis, higher concentrations of proteolytic enzymes, and increased levels of proinflammatory cytokines. In previous studies, we have shown that C-C chemokine ligand (CCL)2, CCL3, and CCL5 are highly expressed by cultured nucleus pulposus (NP) and annulus fibrosus (AF) cells that have been treated by interleukin-1. The major function of these chemokines is to recruit immune cells into the disc. It is unclear if disc cells can respond to these chemokines. Recent studies by Phillips et al. (2015) showed that NP cells express a number of cytokines and chemokine receptors. The purpose of this study is to determine the gene and protein expression of C-C chemokine receptor (CCR)1, CCR2, and CCR5 in NP and AF cells, and to test if these receptors can respond to their ligands in these cells by cell signaling and migration. This is an in vitro study. For RNA, surface expression, and cell signaling studies, human cells were isolated from the NP and AF tissues collected after spine surgery or from donated spine segments (Gift of Hope Human Donor & Tissue Network of Illinois) and cultured in monolayer. The gene expression of human CCR1, CCR2, and CCR5 was analyzed using real-time polymerase chain reaction. The surface expression of CCR1, CCR2, and CCR5 was analyzed using flow cytometry and fluorescently tagged antibodies specific for these proteins. Extracellular signal-regulated kinase (ERK) phosphorylation was analyzed from the cell lysates of NP and AF cells treated with CCL2 and CCL5 for 1 hour using enzyme-linked immunosorbent assay. Migration of primary rabbit AF cells was assayed using 8-µm Corning Transwell inserts in the presence or absence of CCL5. This study was partially funded by a North American Spine Society 2014 Basic Research Grant Award ($50,000). RNA analysis showed that gene expression of CCR1, CCR2, and CCR5 was evident in

  17. News: Good chemical manufacturing process criteria

    Science.gov (United States)

    This news column covers topics relating to manufacturing criteria, machine to machine technology, novel process windows, green chemistry indices, business resilience, immobilized enzymes, and Bt crops.

  18. The News Media as a Political Institution

    DEFF Research Database (Denmark)

    Ørsten, Mark; Allern, Sigurd

    2011-01-01

    On the basis of Scandinavian journalism research this article discusses the changing political roles of news organizations and journalists after the fall of the party press and the dissolution of broadcasting as a state-controlled monopoly. Given these institutional changes, we ask the following......: what new roles, if any, are news organizations and journalists playing in the political system? What are the characteristics of these new roles, and how do news organizations use their newfound political power? We address these questions in the context of an institutional approach to the news coupled...... with Hallin and Mancini's analysis of media systems....

  19. New format for ATLAS e-news

    CERN Multimedia

    Pauline Gagnon

    ATLAS e-news got a new look! As of November 30, 2007, we have a new format for ATLAS e-news. Please go to: http://atlas-service-enews.web.cern.ch/atlas-service-enews/index.html . ATLAS e-news will now be published on a weekly basis. If you are not an ATLAS colaboration member but still want to know how the ATLAS experiment is doing, we will soon have a version of ATLAS e-news intended for the general public. Information will be sent out in due time.

  20. The Usefulness of a News Media Literacy Measure in Evaluating a News Literacy Curriculum

    Science.gov (United States)

    Maksl, Adam; Craft, Stephanie; Ashley, Seth; Miller, Dean

    2017-01-01

    A survey of college students showed those who had taken a news literacy course had significantly higher levels of news media literacy, greater knowledge of current events, and higher motivation to consume news, compared with students who had not taken the course. The effect of taking the course did not diminish over time. Results validate the News…

  1. Young people’s news orientations and uses of traditional and new media for news

    NARCIS (Netherlands)

    van Cauwenberge, A.; d'Haenens, L.; Beentjes, H.

    2013-01-01

    This article reports on Flemish college students’ news orientations and their uses of traditional and new media for news within a public service media environment. We used five homogeneous focus groups that covered variation in news media use. The analysis of the focus groups revealed major

  2. Hierarchical Collaboration in the Revision of Text: Constructing Perceptions of Editorial Conferences in the News Laboratory.

    Science.gov (United States)

    Irby, Janet

    This study of editorial conferences in a university news laboratory examined the connections between dialogues about revision and the interpretations of dialogues by reporters and the editor in this journalism culture. The editorial conferences of two reporters with varying experience in publication and employment settings were analyzed, and the…

  3. Organization of the News Industry

    DEFF Research Database (Denmark)

    Vang, Jan

    2003-01-01

    In this paper the two canonical theories of the firm - transaction costs economics and theknowledge-based view of the firm - predictions on `make-or-buy' are tested on the newsindustry. The news industry provides an interesting case on which to test the two theories sinceit is characterized...... are that that newspapers are organized differentlythan is predicted from the knowledge-based view of the firm and transaction cost economics.The newspapers do no specialize in core competencies measured in terms of topics covered. Onthe contrary, a precondition for outsourcing is well-developed competencies in house...

  4. Miscellaneous news from the world

    International Nuclear Information System (INIS)

    Pradel, J.

    2005-01-01

    Different news from the world, Ukraine hopes to build 11 new nuclear reactors up to 2030, Armenia allows the construction of a for radioactive waste storage (in operation in 50 years), Poland has announced the opening of a nuclear power plant for 2020, Sweden closed the second reactor of the Barsebaeck nuclear power plant on the 31 of may (2005), the energy situation in the Baltic sea region, on February 2005 six governments(Canada, France, Japan, United States, United kingdom, Switzerland) have signed a framework agreement for international collaboration on research and development of generation four nuclear energy systems. Finland does the choice of E.P.R.. (N.C.)

  5. Media Literacy, News Literacy, or News Appreciation? A Case Study of the News Literacy Program at Stony Brook University

    Science.gov (United States)

    Fleming, Jennifer

    2014-01-01

    This case study provides practical and theoretical insights into the Stony Brook news literacy program, which is one of the most ambitious and well-funded curricular experiments in modern journalism education and media literacy. Analysis of document, interview, and observation data indicates that news literacy educators sought to teach students…

  6. Outsourcing the news? An empirical assessment of the role of sources and news agencies in the contemporary news landscape

    NARCIS (Netherlands)

    Boumans, J.W.

    2016-01-01

    Journalists are increasingly accused of uncritically recycling subsidized material in the form of press releases and news agency copy. This practice has been labeled churnalism and is believed to compromise journalism’s autonomy and threaten news quality. While the context - rampant competition,

  7. Chemokine CCL2 and chemokine receptor CCR2 in early active multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Strieter, R M

    2004-01-01

    The chemokine monocyte chemoattractant protein (MCP)-1/CCL2 and its receptor CCR2 have been strongly implicated in disease pathogenesis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS), whereas data on the CCL2-CCR2 axis are scarce in MS. We studied...... the expression of CCR2 on leukocytes in blood and cerebrospinal fluid (CSF) from patients with monosymptomatic optic neuritis and MS, and the concentration of CCL2 in the CSF from these patients. Results were compared with the results in non-inflammatory neurological controls and were correlated with other...... parameters (magnetic resonance imaging and CSF data). Our findings suggest a limited role for CCL2/CCR2 in early active MS....

  8. Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5

    DEFF Research Database (Denmark)

    Berg, Christian; Spiess, Katja; von Lüttichau, Hans Rudolf

    2016-01-01

    Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1...... fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout. Receptor...... expression was evaluated by ELISA and fluorescence microscopy. On CCR5 WT, Maraviroc and Aplaviroc inhibited fusion with high potencies (EC 50 values of 91 and 501 nM, respectively), whereas removal of key residues for both antagonists (Glu283Ala) or Maraviroc alone (Tyr251Ala) prevented fusion inhibition...

  9. [Novel echogenic needle for ultrasound-guided peripheral nerve block "Hakko type CCR"].

    Science.gov (United States)

    Takayama, Wataru; Yasumura, Rie; Kaneko, Takehiko; Kobayashi, Yoshiro; Kamada, Takaaki; Yoshikawa, Tamotsu; Aoyama, Yasuhiko

    2009-04-01

    A novel echogenic insulated nerve block needle (CCR-needle: Echogenic Needle Type CCR; Hakko, Japan) is commercially available since 2006 in Japan. This needle has three echogenic dimples, namely corner cube reflectors (CCR) on its tip. The CCR-needle will potentially provide a significant advantage for detecting the needle tip. In this report, we firstly evaluated this new disposable echogenic needle in simulation phantom, and demonstrated improved visibility of the needle tip. Afterwards, an interscalene brachial plexus block was performed on a male patient undergoing shoulder surgery. The needle insertion procedure was the "out of plane" ultrasound-guided technique using simultaneous electrical nerve stimulation. The surgery was successfully conducted without any complications.

  10. Study progress of CCR3 in wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Xian-Wei Wu

    2014-03-01

    Full Text Available According to the study, chemokine receptor 3(CCR3in the eye is mainly distributed in retinal pigment epithelial cells, and also expressed in the choroidal vascular endothelial cells(CECs. The specificity of CCR3's high expression in wet age-related macular degeneration(AMDwas found, and it is proved that in wet-AMD patients, it plays an important role in the formation of choroidal neovascularization(CNV. In this paper, the structure, function, the problem of current research and the future direction of CCR3 were summarized. It is believed that with the further research on CCR3, it will not only help us to find a new method of wet-AMD diagnosis and treatment, but also may provide an important reference for other CNV disease research and new anti-CNV drugs.

  11. Quantifying CD4/CCR5 Usage Efficiency of HIV-1 Env Using the Affinofile System.

    Science.gov (United States)

    Webb, Nicholas E; Lee, Benhur

    2016-01-01

    Entry of HIV-1 into target cells involves the interaction of the HIV envelope (Env) with both a primary receptor (CD4) and a coreceptor (CXCR4 or CCR5). The relative efficiency with which a particular Env uses these receptors is a major component of cellular tropism in the context of entry and is related to a variety of pathological Env phenotypes (Chikere et al. Virology 435:81-91, 2013). The protocols outlined in this chapter describe the use of the Affinofile system, a 293-based dual-inducible cell line that expresses up to 25 distinct combinations of CD4 and CCR5, as well as the associated Viral Entry Receptor Sensitivity Assay (VERSA) metrics used to summarize the CD4/CCR5-dependent infectivity results. This system allows for high-resolution profiling of CD4 and CCR5 usage efficiency in the context of unique viral phenotypes.

  12. CCR5 as a natural and modulated target for inhibition of HIV.

    Science.gov (United States)

    Burke, Bryan P; Boyd, Maureen P; Impey, Helen; Breton, Louis R; Bartlett, Jeffrey S; Symonds, Geoff P; Hütter, Gero

    2013-12-30

    Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection-this without detrimental effects to the host-and transplantation of CCR5-delta32 stem cells in a patient with HIV ("Berlin patient") achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells.

  13. Structure of the CCR5 Chemokine Receptor-HIV Entry Inhibitor Maraviroc Complex

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Qiuxiang; Zhu, Ya; Li, Jian; Chen, Zhuxi; Han, Gye Won; Kufareva, Irina; Li, Tingting; Ma, Limin; Fenalti, Gustavo; Li, Jing; Zhang, Wenru; Xie, Xin; Yang, Huaiyu; Jiang, Hualiang; Cherezov, Vadim; Liu, Hong; Stevens, Raymond C.; Zhao, Qiang; Wu, Beili [Scripps; (Chinese Aca. Sci.); (UCSD)

    2013-10-21

    The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom–resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor–gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.

  14. News

    Science.gov (United States)

    2006-05-01

    Solar Eclipse: Total eclipse aficionados seek out the best observation spots Schools Lecture: Demonstration lectures: what can go wrong will go wrong… Germany: Bridging the education gap Bangladesh: Workshop on science education assists battle against poverty Australia: Teachers gather to share experiences Meeting: Give the examination boards a grilling US Workshops: Workshops demonstrate some excellent teaching apparatus World Year of Physics: WYP events and activities are a great success in New Zealand

  15. News

    Science.gov (United States)

    2002-09-01

    11-14 Curriculum: Supporting Physics Teaching (11-14) Europe: Sci-tech couldn't be without it! Art-Science: Makrolab in Mountain Year Digital Curriculum: Should the BBC learn from the past? Scotland: Teachers get Rocket Science Malaysia: Controversy over the language medium for science teaching UK Science: Next stage of Science Year announced Special Educational Needs: Science for special needs students Folk Physics: Good vibrations Environment: IoM3 - a move towards sustainability? UK Primary Science: The threat of afternoon science

  16. News

    Science.gov (United States)

    2005-03-01

    Microscopy: Schools to gain remote access to Oxford University-based SEM Canada: Perimeter Institute calls international applicants to its 2005 summer school ASE: ASE 2005 refreshes the teaching parts that other conferences cannot reach Scotland: Glasgow hosts Kelvin exhibition Climate Analysis: Met Office sets up project to predict climate change Wales: Welsh teachers meet at Christ College, Brecon ESERA: ESERA 2005 unveils its conference programme Higher Education: Educators address school-university transition Christmas Lecture Series: Royal Institution supports Christmas Lecture series with interactive CD-ROM Events: UK’s Science Week kicks off in March Grants: PPARC and IOP to provide grants worth up to £400 Camera Competition: Congratulations go to camera winners Teachers’ TV: Teachers’ channel hits the small screen Physics and Music: Foster and Liebeck presentation combines physics and music Science on Stage: SOS gears up for Geneva festival Nanoworld: Hirsch lecture at Oxford focuses on the nanoworld GIREP: GIREP conference aims to raise physics’ profile Course: STELAR offers free radio-communication course

  17. News

    Science.gov (United States)

    2006-09-01

    Energy: Increasing global energy needs require drastic policy changes Germany: Science teachers talk tactics in Bavaria Physics Day: NPL hosts A-level physics day Engineering: ICE members consider the past and the future of engineering IOP Awards: Superb teachers receive awards for their contribution to physics New Zealand: Unlikely location serves up stimulating conference Astronomy: Teaching ideas abound at EAAE event in Spain Mexico: Sharing knowledge about better physics teaching

  18. CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system.

    Science.gov (United States)

    Durrant, Douglas M; Daniels, Brian P; Pasieka, TracyJo; Dorsey, Denise; Klein, Robyn S

    2015-12-15

    Cell-mediated immunity is critical for clearance of central nervous system (CNS) infection with the encephalitic flavivirus, West Nile virus (WNV). Prior studies from our laboratory have shown that WNV-infected neurons express chemoattractants that mediate recruitment of antiviral leukocytes into the CNS. Although the chemokine receptor, CCR5, has been shown to play an important role in CNS host defense during WNV infection, regional effects of its activity within the infected brain have not been defined. We used CCR5-deficient mice and an established murine model of WNV encephalitis to determine whether CCR5 activity impacts on WNV levels within the CNS in a region-specific fashion. Statistical comparisons between groups were made with one- or two-way analysis of variance; Bonferroni's post hoc test was subsequently used to compare individual means. Survival was analyzed by the log-rank test. Analyses were conducted using Prism software (GraphPad Prism). All data were expressed as means ± SEM. Differences were considered significant if P ≤ 0.05. As previously shown, lack of CCR5 activity led to increased symptomatic disease and mortality in mice after subcutaneous infection with WNV. Evaluation of viral burden in the footpad, draining lymph nodes, spleen, olfactory bulb, and cerebellum derived from WNV-infected wild-type, and CCR5(-/-) mice showed no differences between the genotypes. In contrast, WNV-infected, CCR5(-/-) mice exhibited significantly increased viral burden in cortical tissues, including the hippocampus, at day 8 post-infection. CNS regional studies of chemokine expression via luminex analysis revealed significantly increased expression of CCR5 ligands, CCL4 and CCL5, within the cortices of WNV-infected, CCR5(-/-) mice compared with those of similarly infected WT animals. Cortical elevations in viral loads and CCR5 ligands in WNV-infected, CCR5(-/-) mice, however, were associated with decreased numbers of infiltrating mononuclear cells

  19. News Paper | Women in Science | Initiatives | Indian Academy of ...

    Indian Academy of Sciences (India)

    News Paper. News and Articles from Newspapers/Magazines. Level-playing field for women scientists - The Hindu. News item on Women's Day Conference by the National Task Force (DST) for Women in Science. More ...

  20. News and Features Updates from USA.gov

    Data.gov (United States)

    General Services Administration — Stay on top of important government news and information with the USA.gov Updates: News and Features RSS feed. We'll update this feed when we add news and featured...

  1. TERRA NEWS: Sensationalism and Fait-divers on the Internet

    Directory of Open Access Journals (Sweden)

    Carlos Golembiewski

    2011-02-01

    Full Text Available This article presents an analysis of the news program Jornal do Terra (Terra News shown on the Terra website. The study involved two aspects: forms of news presentations on TV, based on studies by Pedro Maciel, and criteria of news value, based on Mário Erbolatto’s view. In addition, we used Luis Arthur Ferraretto’s studies of the news formats used specifically on the radio. The objective of this work was to verify what kind of news is transmitted by the news program Terra News, and to compare it with the traditional news program we watch on TV. The study confirmed that Terra News utilizes conventional formats of news presentation and makes a selection of sensationalist news about fait-divers.

  2. Terra News: sensationalism and fait-divers on the Internet

    Directory of Open Access Journals (Sweden)

    Carlos Golembiewski

    2009-12-01

    Full Text Available This article presents an analysis of the news program Jornal do Terra (Terra News shown on the Terra website. The study involved two aspects: forms of news presentations on TV, based on studies by Pedro Maciel, and criteria of news value, based on Mário Erbolatto’s view. In addition, we used Luis Arthur Ferraretto’s studies of the news formats used specifically on the radio. The objective of this work was to verify what kind of news is transmitted by the news program Terra News, and to compare it with the traditional news program we watch on TV. The study confirmed that Terra News utilizes conventional formats of news presentation and makes a selection of sensationalist news about fait-divers.

  3. CCR7 expressing mesenchymal stem cells potently inhibit graft-versus-host disease by spoiling the fourth supplemental Billingham's tenet.

    Directory of Open Access Journals (Sweden)

    Hong Li

    Full Text Available The clinical acute graft-versus-host disease (GvHD-therapy of mesenchymal stem cells (MSCs is not as satisfactory as expected. Secondary lymphoid organs (SLOs are the major niches serve to initiate immune responses or induce tolerance. Our previous study showed that CCR7 guide murine MSC line C3H10T1/2 migrating to SLOs. In this study, CCR7 gene was engineered into murine MSCs by lentivirus transfection system (MSCs/CCR7. The immunomodulatory mechanism of MSCs/CCR7 was further investigated. Provoked by inflammatory cytokines, MSCs/CCR7 increased the secretion of nitric oxide and calmed down the T cell immune response in vitro. Immunofluorescent staining results showed that transfused MSCs/CCR7 can migrate to and relocate at the appropriate T cell-rich zones within SLOs in vivo. MSCs/CCR7 displayed enhanced effect in prolonging the survival and alleviating the clinical scores of the GvHD mice than normal MSCs. Owing to the critical relocation sites, MSCs/CCR7 co-infusion potently made the T cells in SLOs more naïve like, thus control T cells trafficking from SLOs to the target organs. Through spoiling the fourth supplemental Billingham's tenet, MSCs/CCR7 potently inhibited the development of GvHD. The study here provides a novel therapeutic strategy of MSCs/CCR7 infusion at a low dosage to give potent immunomodulatory effect for clinical immune disease therapy.

  4. Concordance of CCR5 Genotypes that Influence Cell-Mediated Immunity and HIV-1 Disease Progression Rates

    Science.gov (United States)

    Catano, Gabriel; Chykarenko, Zoya A.; Mangano, Andrea; Anaya, J-M; Smith, Alison; Bologna, Rosa; Sen, Luisa; Clark, Robert A.; Lloyd, Andrew; Shostakovich-Koretskaya, Ludmila

    2011-01-01

    We used cutaneous delayed-type hypersensitivity responses, a powerful in vivo measure of cell-mediated immunity, to evaluate the relationships among cell-mediated immunity, AIDS, and polymorphisms in CCR5, the HIV-1 coreceptor. There was high concordance between CCR5 polymorphisms and haplotype pairs that influenced delayed-type hypersensitivity responses in healthy persons and HIV disease progression. In the cohorts examined, CCR5 genotypes containing -2459G/G (HHA/HHA, HHA/HHC, HHC/HHC) or -2459A/A (HHE/HHE) associated with salutary or detrimental delayed-type hypersensitivity and AIDS phenotypes, respectively. Accordingly, the CCR5-Δ32 allele, when paired with non-Δ32-bearing haplotypes that correlate with low (HHA, HHC) versus high (HHE) CCR5 transcriptional activity, associates with disease retardation or acceleration, respectively. Thus, the associations of CCR5-Δ32 heterozygosity partly reflect the effect of the non-▵32 haplotype in a background of CCR5 haploinsufficiency. The correlations of increased delayed-type hypersensitivity with -2459G/G-containing CCR5 genotypes, reduced CCR5 expression, decreased viral replication, and disease retardation suggest that CCR5 may influence HIV infection and AIDS, at least in part, through effects on cell-mediated immunity. PMID:21288827

  5. Haplotypes in CCR5-CCR2, CCL3 and CCL5 are associated with natural resistance to HIV-1 infection in a Colombian cohort.

    Science.gov (United States)

    Vega, Jorge A; Villegas-Ospina, Simón; Aguilar-Jiménez, Wbeimar; Rugeles, María T; Bedoya, Gabriel; Zapata, Wildeman

    2017-06-01

    Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls). Haplotypes were inferred using the Arlequin software, and their frequency in individual or combined loci was compared between cases and controls by the chi-square test. A p' value ;0.05 after Bonferroni correction was considered significant. Homozygosis of the human haplogroup (HH) E was absent in controls and frequent in cases, showing a tendency to susceptibility. The haplotypes C-C and T-T in CCL3 were associated with susceptibility (p'=0.016) and resistance (p';0.0001) to HIV-1 infection, respectively. Finally, in multilocus analysis, the haplotype combinations formed by HHC in CCR5-CCR2, T-T in CCL3 and G-C in CCL5 were associated with resistance (p'=0.006). Our results suggest that specific combinations of variants in genes from the same signaling pathway can define an HIV-1 resistant phenotype. Despite our small sample size, our statistically significant associations suggest strong effects; however, these results should be further validated in larger cohorts.

  6. Internalization of the chemokine receptor CCR4 can be evoked by orthosteric and allosteric receptor antagonists.

    Science.gov (United States)

    Ajram, Laura; Begg, Malcolm; Slack, Robert; Cryan, Jenni; Hall, David; Hodgson, Simon; Ford, Alison; Barnes, Ashley; Swieboda, Dawid; Mousnier, Aurelie; Solari, Roberto

    2014-04-15

    The chemokine receptor CCR4 has at least two natural agonist ligands, MDC (CCL22) and TARC (CCL17) which bind to the same orthosteric site with a similar affinity. Both ligands are known to evoke chemotaxis of CCR4-bearing T cells and also elicit CCR4 receptor internalization. A series of small molecule allosteric antagonists have been described which displace the agonist ligand, and inhibit chemotaxis. The aim of this study was to determine which cellular coupling pathways are involved in internalization, and if antagonists binding to the CCR4 receptor could themselves evoke receptor internalization. CCL22 binding coupled CCR4 efficiently to β-arrestin and stimulated GTPγS binding however CCL17 did not couple to β-arrestin and only partially stimulated GTPγS binding. CCL22 potently induced internalization of almost all cell surface CCR4, while CCL17 showed only weak effects. We describe four small molecule antagonists that were demonstrated to bind to two distinct allosteric sites on the CCR4 receptor, and while both classes inhibited agonist ligand binding and chemotaxis, one of the allosteric sites also evoked receptor internalization. Furthermore, we also characterize an N-terminally truncated version of CCL22 which acts as a competitive antagonist at the orthosteric site, and surprisingly also evokes receptor internalization without demonstrating any agonist activity. Collectively this study demonstrates that orthosteric and allosteric antagonists of the CCR4 receptor are capable of evoking receptor internalization, providing a novel strategy for drug discovery against this class of target. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  7. CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives.

    Science.gov (United States)

    Wei, Robert G; Arnaiz, Damian O; Chou, Yuo-Ling; Davey, Dave; Dunning, Laura; Lee, Wheeseong; Lu, Shou-Fu; Onuffer, James; Ye, Bin; Phillips, Gary

    2007-01-01

    High throughput screening (HTS) led to the identification of the guanylhydrazone of 2-(4-chlorobenzyloxy)-5-bromobenzaldehyde as a CCR5 receptor antagonist. Initial modifications of the guanylhydrazone series indicated that substitution of the benzyl group at the para-position was well tolerated. Substitution at the 5-position of the central phenyl ring was critical for potency. Replacement of the guanylhydrazone group led to the discovery of a novel series of CCR5 antagonists.

  8. Ccr2 deletion dissociates cavity size and tau pathology after mild traumatic brain injury.

    Science.gov (United States)

    Gyoneva, Stefka; Kim, Daniel; Katsumoto, Atsuko; Kokiko-Cochran, O Nicole; Lamb, Bruce T; Ransohoff, Richard M

    2015-12-03

    Millions of people experience traumatic brain injury (TBI) as a result of falls, car accidents, sports injury, and blast. TBI has been associated with the development of neurodegenerative conditions such as Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). In the initial hours and days, the pathology of TBI comprises neuronal injury, breakdown of the blood-brain barrier, and inflammation. At the cellular level, the inflammatory reaction consists of responses by brain-resident microglia, astrocytes, and vascular elements as well as infiltration of peripheral cells. After TBI, signaling by chemokine (C-C motif) ligand 2 (CCL2) to the chemokine (C-C motif) receptor 2 (CCR2) is a key regulator of brain infiltration by monocytes. We utilized mice with one or both copies of Ccr2 disrupted by red fluorescent protein (RFP, Ccr2 (RFP/+) and Ccr2 (RFP/RFP) ). We subjected these mice to the mild lateral fluid percussion model of TBI and examined several pathological outcomes 3 days later in order to determine the effects of altered monocyte entry into the brain. Ccr2 deletion reduced monocyte infiltration, diminished lesion cavity volume, and lessened axonal damage after mild TBI, but the microglial reaction to the lesion was not affected. We further examined phosphorylation of the microtubule-associated protein tau, which aggregates in brains of people with TBI, AD, and CTE. Surprisingly, Ccr2 deletion was associated with increased tau mislocalization to the cell body in the cortex and hippocampus by tissue staining and increased levels of phosphorylated tau in the hippocampus by Western blot. Disruption of CCR2 enhanced tau pathology and reduced cavity volume in the context of TBI. The data reveal a complex role for CCR2(+) monocytes in TBI, as monitored by cavity volume, axonal damage, and tau phosphorylation.

  9. Frequency of CCR5Δ32 allele in healthy Bosniak population.

    Directory of Open Access Journals (Sweden)

    Grażyna Adler

    2014-08-01

    Full Text Available Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12% and lower in the regions of Southeast Mediterranean (about 5%. Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013.  Mean age of the cohort being 58.8 (±10.7 years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. 

  10. Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5.

    Science.gov (United States)

    Berg, Christian; Spiess, Katja; Lüttichau, Hans R; Rosenkilde, Mette M

    2016-12-01

    Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor antagonists for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 agonists as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV Env and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout. Receptor expression was evaluated by ELISA and fluorescence microscopy. On CCR5 WT, Maraviroc and Aplaviroc inhibited fusion with high potencies (EC 50 values of 91 and 501 nM, respectively), whereas removal of key residues for both antagonists (Glu283Ala) or Maraviroc alone (Tyr251Ala) prevented fusion inhibition, establishing this assay as suitable for screening of HIV entry inhibitors. Both ligands inhibited HIV fusion on signaling-deficient CCR5 mutations (Tyr244Ala and Trp248Ala). Moreover, the steric hindrance CCR5 mutation (Gly286Phe) impaired fusion, presumably by a direct hindrance of gp120 interaction. Finally, the efficacy switch mutation (Leu203Phe) - converting small-molecule antagonists/inverse agonists to full agonists biased toward G-protein activation - uncovered that also small-molecule agonists can function as direct HIV-1 cell entry inhibitors. Importantly, no agonist-induced receptor internalization was observed for this mutation. Our studies of the pharmacodynamic requirements for HIV-1 fusion inhibitors highlight the possibility of future development of biased ligands with selective targeting of the HIV-CCR5 interaction without interfering with the normal functionality of CCR5.

  11. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Torsten A Krause

    Full Text Available Age-related macular degeneration (AMD is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF. Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source

  12. News from Council - September 2016

    CERN Multimedia

    2016-01-01

    I would like to inform you of the main news from the Council this week. First of all, the Council congratulated CERN and the Collaborations on the superb performance of the accelerator complex and experiments. It has been a great year so far, with important physics results across the whole spectrum of the CERN research programme.   Looking forward, one of the main accomplishments from this week’s meetings is that the Council has approved the opening of a credit facility with the European Investment Bank (EIB) to cover the cash shortage during the peak years of the High-Luminosity LHC (HL-LHC) construction. This is very good news since it will allow us to carry out the work necessary for the HL-LHC without compromising the rest of the Laboratory’s scientific programme. Turning to the scientific and geographical enlargement, the Council approved the admission of India as an Associate Member State, and I very much hope that the agreement can be signed in the near future so that Indi...

  13. The NEWS Water Cycle Climatology

    Science.gov (United States)

    Rodell, Matthew; Beaudoing, Hiroko Kato; L'Ecuyer, Tristan; William, Olson

    2012-01-01

    NASA's Energy and Water Cycle Study (NEWS) program fosters collaborative research towards improved quantification and prediction of water and energy cycle consequences of climate change. In order to measure change, it is first necessary to describe current conditions. The goal of the first phase of the NEWS Water and Energy Cycle Climatology project was to develop "state of the global water cycle" and "state of the global energy cycle" assessments based on data from modern ground and space based observing systems and data integrating models. The project was a multi-institutional collaboration with more than 20 active contributors. This presentation will describe the results of the water cycle component of the first phase of the project, which include seasonal (monthly) climatologies of water fluxes over land, ocean, and atmosphere at continental and ocean basin scales. The requirement of closure of the water budget (i.e., mass conservation) at various scales was exploited to constrain the flux estimates via an optimization approach that will also be described. Further, error assessments were included with the input datasets, and we examine these in relation to inferred uncertainty in the optimized flux estimates in order to gauge our current ability to close the water budget within an expected uncertainty range.

  14. Connected Traveler

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Alex

    2015-11-01

    The Connected Traveler project is a multi-disciplinary undertaking that seeks to validate potential for transformative transportation system energy savings by incentivizing efficient traveler behavior. This poster outlines various aspects of the Connected Traveler project, including market opportunity, understanding traveler behavior and decision-making, automation and connectivity, and a projected timeline for Connected Traveler's key milestones.

  15. CCL5 and CCR5 interaction promotes cell motility in human osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Shih-Wei Wang

    Full Text Available BACKGROUND: Osteosarcoma is characterized by a high malignant and metastatic potential. CCL5 (previously called RANTES was originally recognized as a product of activated T cells, and plays a crucial role in the migration and metastasis of human cancer cells. It has been reported that the effect of CCL5 is mediated via CCR receptors. However, the effect of CCL5 on migration activity and integrin expression in human osteosarcoma cells is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we found that CCL5 increased the migration and expression of αvβ3 integrin in human osteosarcoma cells. Stimulation of cells with CCL5 increased CCR5 but not CCR1 and CCR3 expression. CCR5 mAb, inhibitor, and siRNA reduced the CCL5-enhanced the migration and integrin up-regulation of osteosarcoma cells. Activations of MEK, ERK, and NF-κB pathways after CCL5 treatment were demonstrated, and CCL5-induced expression of integrin and migration activity was inhibited by the specific inhibitor and mutant of MEK, ERK, and NF-κB cascades. In addition, over-expression of CCL5 shRNA inhibited the migratory ability and integrin expression in osteosarcoma cells. CONCLUSIONS/SIGNIFICANCE: CCL5 and CCR5 interaction acts through MEK, ERK, which in turn activates NF-κB, resulting in the activations of αvβ3 integrin and contributing the migration of human osteosarcoma cells.

  16. Functional characterization of CCR in birch (Betula platyphylla × Betula pendula) through overexpression and suppression analysis.

    Science.gov (United States)

    Zhang, Wenbo; Wei, Rui; Chen, Su; Jiang, Jing; Li, Huiyu; Huang, Haijiao; Yang, Guang; Wang, Shuo; Wei, Hairong; Liu, Guifeng

    2015-06-01

    We cloned a Cinnamoyl-CoA Reductase gene (BpCCR1) from an apical meristem and first internode of Betula platyphylla and characterized its functions in lignin biosynthesis, wood formation and tree growth through transgenic approaches. We generated overexpression and suppression transgenic lines and analyzed them in comparison with the wild-type in terms of lignin content, anatomical characteristics, height and biomass. We found that BpCCR1 overexpression could increase lignin content up to 14.6%, and its underexpression decreased lignin content by 6.3%. Surprisingly, modification of BpCCR1 expression led to conspicuous changes in wood characteristics, including xylem vessel number and arrangement, and secondary wall thickness. The growth of transgenic trees in terms of height was also significantly influenced by the modification of BpCCR1 genes. We discuss the functions of BpCCR1 in the context of a phylogenetic tree built with CCR genes from multiple species. © 2014 Scandinavian Plant Physiology Society.

  17. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape.

    Science.gov (United States)

    Hütter, Gero; Bodor, Josef; Ledger, Scott; Boyd, Maureen; Millington, Michelle; Tsie, Marlene; Symonds, Geoff

    2015-07-27

    Allogeneic transplantation with CCR5-delta 32 (CCR5-d32) homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC) to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), transcription activator-like effectors nuclease (TALEN), short hairpin RNA (shRNA), and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  18. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

    Directory of Open Access Journals (Sweden)

    Gero Hütter

    2015-07-01

    Full Text Available Allogeneic transplantation with CCR5-delta 32 (CCR5-d32 homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN, clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9, transcription activator-like effectors nuclease (TALEN, short hairpin RNA (shRNA, and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  19. TV News Analysis Project Motivates Broadcast Class.

    Science.gov (United States)

    Smith, James R.

    1980-01-01

    Describes the use of content analysis by a journalism class in studying television news. Indicates that the method is flexible, generates familiarity with quantitative approaches to the analysis of broadcast journalism, can result in increased awareness of the complexity of the broadcast news medium, and increases student motivation. (TJ)

  20. News Analytics for Financial Decision Support

    NARCIS (Netherlands)

    V. Milea (Viorel)

    2013-01-01

    textabstractThis PhD thesis contributes to the newly emerged, growing body of scientific work on the use of News Analytics in Finance. Regarded as the next significant development in Automated Trading, News Analytics extends trading algorithms to incorporate information extracted from textual

  1. Workforce Competitiveness Collection. "LINCS" Resource Collection News

    Science.gov (United States)

    Literacy Information and Communication System, 2011

    2011-01-01

    This edition of "'LINCS' Resource Collection News" features the Workforce Competitiveness Collection, covering the topics of workforce education, English language acquisition, and technology. Each month Collections News features one of the three "LINCS" (Literacy Information and Communication System) Resource Collections--Basic…

  2. Data Exchanges in Mobile News Apps

    DEFF Research Database (Denmark)

    Kammer, Aske; Wallberg, Filip

    This paper maps the flows of data to and from third-party actors when users access content in mobile news apps. This way, it analyzes the strategic networks of collaboration and data exchange that news organizations engage in in the digital economy, expanding the traditional two-sided model...

  3. Breaking Bad News - Perceptions of Pediatric Residents.

    Science.gov (United States)

    Geeta, M G; Krishnakumar, P

    2017-08-15

    The present study evaluated the perceptions and practice of 92 final year pediatric residents with regard to breaking bad news. Only 16% of residents had received any training in communication skills. Majority (65%) of the residents were not comfortable while breaking bad news.

  4. Television news and fear; A child survey

    NARCIS (Netherlands)

    Walma van der Molen, J.H.; Valkenburg, P.M.; Peeters, A.L.

    2002-01-01

    Using telephone interviews among a random sample of 537 Dutch children aged 7–12 years old, we investigated (a) the prevalence of fear reactions to television news among younger and older children and among boys and girls, (b) what types of news items children in different age and gender groups

  5. Fight or flight: Affective news framing effects

    NARCIS (Netherlands)

    Feinholdt, A.

    2016-01-01

    This dissertation investigates how emotions shape and are shaped by news framing and how this interplay leads to a number of affective news framing effects. My work reveals that emotions do not only function as mechanisms but also as channels strengthening or weakening framing effects. In addition,

  6. Automatic Amharic text news classification: Aneural networks ...

    African Journals Online (AJOL)

    The study is on classification of Amharic news automatically using neural networks approach. Learning Vector Quantization (LVQ) algorithm is employed to classify new instance of Amharic news based on classifier developed using training dataset. Two weighting schemes, Term Frequency (TF) and Term Frequency by ...

  7. Developing a News Media Literacy Scale

    Science.gov (United States)

    Ashley, Seth; Maksl, Adam; Craft, Stephanie

    2013-01-01

    Using a framework previously applied to other areas of media literacy, this study developed and assessed a measurement scale focused specifically on critical news media literacy. Our scale appears to successfully measure news media literacy as we have conceptualized it based on previous research, demonstrated through assessments of content,…

  8. Resonance – Journal of Science Education | News

    Indian Academy of Sciences (India)

    pp 64-66 General Article. Fulfilling Mendeleev's Dream · A G Samuelson · More Details Fulltext PDF. pp 67-73 General Article. Glenn Seaborg 1912-1999 ... More Details Fulltext PDF. pp 91-95 Research News. Nobel Prize in Physiology or Medicine 1999 · Utpal Tatu · More Details Fulltext PDF. pp 95-100 Research News.

  9. News Values and the Vividness of Information.

    Science.gov (United States)

    Kennamer, J. David

    Most journalism textbooks begin with lists of what have been called "news values." These are criteria to be used to judge the newsworthiness of issues, events, and persons. The list of news values that most journalists have memorized can be replaced with a single concept--vividness. Vividness is a characteristic of the information…

  10. Program Management Collection. "LINCS" Resource Collection News

    Science.gov (United States)

    Literacy Information and Communication System, 2011

    2011-01-01

    This edition of "'LINCS' Resource Collection News" features the Program Management Collection, which covers the topics of Assessment, Learning Disabilities, and Program Improvement. Each month Collections News features one of the three "LINCS" (Literacy Information and Communication System) Resource Collections--Basic Skills, Program Management,…

  11. The Places and Spaces of News Audiences

    DEFF Research Database (Denmark)

    Historically, or so we would like to believe, the story of everyday life for many people included regular, definitive moments of news consumption. Journalism, in fact, was distributed around these routines: papers were delivered before breakfast, the evening news on TV buttressed the transition...

  12. Resonance – Journal of Science Education | News

    Indian Academy of Sciences (India)

    pp 68-72 Research News. Fascinating Shapes and Structures Due to Entropic Forces · Kheya Sengupta Kattera A Suresh · More Details Fulltext PDF. pp 73-75 Research News. Adaptive Significance of Circadian Rhythms - Biological Clocks and Darwinian Fitness in Cyanobacteria · V Sheeba Vijay Kumar Sharma Amitabh ...

  13. Resonance – Journal of Science Education | News

    Indian Academy of Sciences (India)

    More Details Fulltext PDF. Volume 4 Issue 1 January 1999 pp 73-75 Research News. Adaptive Significance of Circadian Rhythms - Biological Clocks and Darwinian Fitness in Cyanobacteria · V Sheeba Vijay Kumar Sharma Amitabh Joshi · More Details Fulltext PDF. Volume 4 Issue 3 March 1999 pp 77-80 Research News.

  14. Press problem related to nuclear energy news reporting

    International Nuclear Information System (INIS)

    Arai, Mitsuo

    2008-01-01

    Since the event of Niigataken Chuetsu-oki Earthquake in 2007 and the subsequent press reports on damage of nuclear power station after it, a stance of media is being questioned. In order to clear this problem, basic organizational structure of the press related to nuclear energy news was analyzed. Local news department, social news department, science news department and economical news department involve in nuclear energy news the accordance with their own situations and concerns. This structure makes problem of nuclear energy news reporting complicated. Changing this system is required but very difficult. It is concluded that the press problem around nuclear energy news is strange. (author)

  15. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice.

    Directory of Open Access Journals (Sweden)

    Noah Saederup

    2010-10-01

    Full Text Available Monocyte subpopulations distinguished by differential expression of chemokine receptors CCR2 and CX3CR1 are difficult to track in vivo, partly due to lack of CCR2 reagents.We created CCR2-red fluorescent protein (RFP knock-in mice and crossed them with CX3CR1-GFP mice to investigate monocyte subset trafficking. In mice with experimental autoimmune encephalomyelitis, CCR2 was critical for efficient intrathecal accumulation and localization of Ly6C(hi/CCR2(hi monocytes. Surprisingly, neutrophils, not Ly6C(lo monocytes, largely replaced Ly6C(hi cells in the central nervous system of these mice. CCR2-RFP expression allowed the first unequivocal distinction between infiltrating monocytes/macrophages from resident microglia.These results refine the concept of monocyte subsets, provide mechanistic insight about monocyte entry into the central nervous system, and present a novel model for imaging and quantifying inflammatory myeloid populations.

  16. Transmitted/Founder and Chronic HIV-1 Envelope Proteins Are Distinguished by Differential Utilization of CCR5

    Science.gov (United States)

    Parker, Zahra F.; Iyer, Shilpa S.; Wilen, Craig B.; Parrish, Nicholas F.; Chikere, Kelechi C.; Lee, Fang-Hua; Didigu, Chuka A.; Berro, Reem; Klasse, Per Johan; Lee, Benhur; Moore, John P.; Shaw, George M.

    2013-01-01

    Infection by HIV-1 most often results from the successful transmission and propagation of a single virus variant, termed the transmitted/founder (T/F) virus. Here, we compared the attachment and entry properties of envelope (Env) glycoproteins from T/F and chronic control (CC) viruses. Using a panel of 40 T/F and 47 CC Envs, all derived by single genome amplification, we found that 52% of clade C and B CC Envs exhibited partial resistance to the CCR5 antagonist maraviroc (MVC) on cells expressing high levels of CCR5, while only 15% of T/F Envs exhibited this same property. Moreover, subtle differences in the magnitude with which MVC inhibited infection on cells expressing low levels of CCR5, including primary CD4+ T cells, were highly predictive of MVC resistance when CCR5 expression levels were high. These results are consistent with previous observations showing a greater sensitivity of T/F Envs to MVC inhibition on cells expressing very high levels of CCR5 and indicate that CC Envs are often capable of recognizing MVC-bound CCR5, albeit inefficiently on cells expressing physiologic levels of CCR5. When CCR5 expression levels are high, this phenotype becomes readily detectable. The utilization of drug-bound CCR5 conformations by many CC Envs was seen with other CCR5 antagonists, with replication-competent viruses, and did not obviously correlate with other phenotypic traits. The striking ability of clade C and B CC Envs to use MVC-bound CCR5 relative to T/F Envs argues that the more promiscuous use of CCR5 by these Env proteins is selected against at the level of virus transmission and is selected for during chronic infection. PMID:23269796

  17. Distribution of the CCR5delta32 allele (gene variant CCR5) in Rondônia, Western Amazonian region, Brazil

    Science.gov (United States)

    de Farias, Josileide Duarte; Santos, Marlene Guimarães; de França, Andonai Krauze; Delani, Daniel; Tada, Mauro Shugiro; Casseb, Almeida Andrade; Simões, Aguinaldo Luiz; Engracia, Vera

    2012-01-01

    Since around 1723, on the occasion of its initial colonization by Europeans, Rondonia has received successive waves of immigrants. This has been further swelled by individuals from northeastern Brazil, who began entering at the beginning of the twentieth century. The ethnic composition varies across the state according to the various sites of settlement of each wave of immigrants. We analyzed the frequency of the CCR5Δ32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in five sample sets from the population. Four were collected in Porto Velho, the state capital and the site of several waves of migration. Of these, two, from the Hospital de Base were comprised of HB Mothers and HB Newborns presenting allele frequencies of 3.5% and 3.1%, respectively, a third from the peri-urban neighborhoods of Candelária/Bate-Estaca (1.8%), whereas a fourth, from the Research Center on Tropical Medicine/CEPEM (0.6%), was composed of malaria patients under treament. The fifth sample (3.4%) came from the inland Quilombola village of Pedras Negras. Two homozygous individuals (CCR5Δ32/CCR5Δ32) were detected among the HB Mother samples. The frequency of this allele was heterogeneous and higher where the European inflow was more pronounced. The presence of the allele in Pedras Negras revealed European miscegenation in a community largely comprising Quilombolas. PMID:22481870

  18. Heroin use in Indonesia is associated with higher expression of CCR5 on CD4+ cells and lower ex-vivo production of CCR5 ligands

    NARCIS (Netherlands)

    Meijerink, H.; Indrati, A.R.; Soedarmo, S.; Utami, F.; Jong, C.A.J. de; Alisjahbana, B.; Crevel, R. van; Wisaksana, R.; Ven, A.J.A.M. van der

    2015-01-01

    Opioid use may affect HIV infection through altered expression of HIV co-receptors. This was examined in Indonesia among antiretroviral therapy-naive HIV patients, many of whom use drugs. C-C chemokine receptor type 5 (CCR5) expression on CD4+ cells was higher in heroin (P = 0.007), methadone

  19. Possible Impact of 190G > A CCR2 and Δ32 CCR5 Mutations on Decrease of the HBV Vaccine Immunogenicity—A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Maria Ganczak

    2017-02-01

    Full Text Available Background: Chemokine genetic variations are involved in infectious diseases such as hepatitis B virus (HBV. Several allelic variants might, in theory, affect the outcome of vaccination. Objectives: This study was carried out to examine the associations of Δ32 CCR5 and 190G > A CCR2 polymorphisms with a response to a primary course of three HBV vaccinations. Methods: Between December 2014 and December 2016, patients from three randomly selected primary care clinics in the West Pomeranian region (Poland, 1 month after receiving the third dose of HBV vaccine, were enrolled. Enzyme-linked immunosorbent assay (ELISA system version 3.0 was used to detect anti-HBs and anti-HBc totals. The identification of polymorphisms were performed by a polymerase chain reaction technique using a single primer extension assay. Genotype distributions of responders versus non-responders to HBV vaccination were compared on the basis of anti-HBs level. Results: In 149 patients (mean age 60 years the mean anti-HBs level was 652.2 ± 425.9 mIU/mL (range: 0–1111.0 mIU/mL. There were 14.1% (n = 21 non-responders to the HBV vaccine (anti-HBs < 10.0 mIU/mL. The wild type/Δ32 genotype of CCR5 gene was found in 18.1% participants, and 1.3% were Δ32/Δ32 homozygotes. The frequency of allele A of the CCR2 gene was 11.1%. Lower anti-HBs levels in Δ32/Δ32 homozygotes were observed (Me = 61 mIU/mL vs. Me = 660.2 mIU/mL; p = 0.048. As age was found to be a correlate to the anti-HBs titer (r = −0.218, p = 0.0075; 95% CI: −0.366–−0.059—an analysis of a co-variance was performed which found a statistically significant (p = 0.04 difference in anti-HBs titres between Δ32/Δ32 homozygotes and other CCR5 genotypes. The association between anti-HBs titres and CCR2 genotypes was not statistically significant. Conclusions: Our study—which is a preliminary report that suggest this topic deserves further observation with larger sample sizes, different ethnicities, and other

  20. Exacerbation of Facial Motoneuron Loss after Facial Nerve Axotomy in CCR3-Deficient Mice

    Directory of Open Access Journals (Sweden)

    Derek A Wainwright

    2009-11-01

    Full Text Available We have previously demonstrated a neuroprotective mechanism of FMN (facial motoneuron survival after facial nerve axotomy that is dependent on CD4+ Th2 cell interaction with peripheral antigen-presenting cells, as well as CNS (central nervous system-resident microglia. PACAP (pituitary adenylate cyclase-activating polypeptide is expressed by injured FMN and increases Th2-associated chemokine expression in cultured murine microglia. Collectively, these results suggest a model involving CD4+ Th2 cell migration to the facial motor nucleus after injury via microglial expression of Th2-associated chemokines. However, to respond to Th2-associated chemokines, Th2 cells must express the appropriate Th2-associated chemokine receptors. In the present study, we tested the hypothesis that Th2-associated chemokine receptors increase in the facial motor nucleus after facial nerve axotomy at timepoints consistent with significant T-cell infiltration. Microarray analysis of Th2-associated chemokine receptors was followed up with real-time PCR for CCR3, which indicated that facial nerve injury increases CCR3 mRNA levels in mouse facial motor nucleus. Unexpectedly, quantitative- and co-immunofluorescence revealed increased CCR3 expression localizing to FMN in the facial motor nucleus after facial nerve axotomy. Compared with WT (wild-type, a significant decrease in FMN survival 4 weeks after axotomy was observed in CCR3–/– mice. Additionally, compared with WT, a significant decrease in FMN survival 4 weeks after axotomy was observed in Rag2 –/– (recombination activating gene-2-deficient mice adoptively transferred CD4+ T-cells isolated from CCR3–/– mice, but not in CCR3–/– mice adoptively transferred CD4+ T-cells derived from WT mice. These results provide a basis for further investigation into the co-operation between CD4+ T-cell- and CCR3-mediated neuroprotection after FMN injury.

  1. CCR7 Modulates the Generation of Thymic Regulatory T Cells by Altering the Composition of the Thymic Dendritic Cell Compartment

    Directory of Open Access Journals (Sweden)

    Zicheng Hu

    2017-10-01

    Full Text Available Upon recognition of auto-antigens, thymocytes are negatively selected or diverted to a regulatory T cell (Treg fate. CCR7 is required for negative selection of auto-reactive thymocytes in the thymic medulla. Here, we describe an unanticipated contribution of CCR7 to intrathymic Treg generation. Ccr7−/− mice have increased Treg cellularity because of a hematopoietic but non-T cell autonomous CCR7 function. CCR7 expression by thymic dendritic cells (DCs promotes survival of mature Sirpα− DCs. Thus, CCR7 deficiency results in apoptosis of Sirpα− DCs, which is counterbalanced by expansion of immature Sirpα+ DCs that efficiently induce Treg generation. CCR7 deficiency results in enhanced intrathymic generation of Tregs at the neonatal stage and in lymphopenic adults, when Treg differentiation is critical for establishing self-tolerance. Together, these results reveal a complex function for CCR7 in thymic tolerance induction, where CCR7 not only promotes negative selection but also governs intrathymic Treg generation via non-thymocyte intrinsic mechanisms.

  2. CCR9+ T cells contribute to the resolution of the inflammatory response in a mouse model of intestinal amoebiasis.

    Science.gov (United States)

    Rojas-López, A E; Soldevila, G; Meza-Pérez, S; Dupont, G; Ostoa-Saloma, P; Wurbel, M A; Ventura-Juárez, J; Flores-Romo, L; García-Zepeda, E A

    2012-08-01

    Analysis of the mechanisms underlying the inflammatory response in amoebiasis is important to understand the immunopathology of the disease. Mucosal associated effector and regulatory T cells may play a role in regulating the inflammatory immune response associated to Entamoeba histolytica infection in the colon. A subpopulation of regulatory T cells has recently been identified and is characterized by the expression of the chemokine receptor CCR9. In this report, we used CCR9 deficient (CCR9(-/-)) mice to investigate the role of the CCR9(+) T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9(+/+), CCR9(+/-) and CCR9(-/-) mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9(+/+) and CCR9(+/-) mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9(-/-) mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-γ, TNF-α, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition, increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in CCR9(-/-) mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9(-/-) mice at seven days post infection (pi), whereas in CCR9(+/+) mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9(-/-) mice, was associated with a delayed recruitment of CD4(+)CD25(+)FoxP3(+) T cells to the cecal epithelium and lamina propria, suggesting that this population may play a role in the early regulation of the inflammatory response against E. histolytica, likely through IL-10 production. In support of these data, CCR9(+) T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9(+)CD4(+)CD25(+)FoxP3(+) T cells may

  3. Breaking bad news in cancer patients.

    Science.gov (United States)

    Konstantis, Apostolos; Exiara, Triada

    2015-01-01

    In a regional hospital, many patients are newly diagnosed with cancer. Breaking the bad news in these patients and their relatives is a tough task. Many doctors are not experienced in talking to patients about death or death-related diseases. In recent years, there have been great efforts to change the current situation. The aim of this study was to investigate the experience and education of medical personnel in breaking bad news in a secondary hospital. 59 doctors from General Hospital of Komotini, Greece were included in the study. All the doctors were in clinical specialties that treated cancer patients. A brief questionnaire was developed based on current guidelines such as Baile/SPIKES framework and the ABCDE mnemonic. Residents are involved in delivering bad news less frequently than specialists. Only 21 doctors (35.59%) had specific training on breaking bad news. 20 doctors (33.90%) were aware of the available techniques and protocols on breaking bad news. 47 doctors (79.66%) had a consistent plan for breaking bad news. 57 (96.61%) delivered bad news in a quiet place, 53 (89.83%) ensured no interruptions and enough time, 53 (89.83%) used simple words and 54 (91.53%) checked for understanding and did not rush through the news. 46 doctors (77.97%) allowed relatives to determine patient's knowledge about the disease. There were low rates of specific training in breaking bad news. However, the selected location, the physician's speech and their plan were according to current guidelines.

  4. Breaking bad news in cancer patients

    Directory of Open Access Journals (Sweden)

    Apostolos Konstantis

    2015-01-01

    Full Text Available Objective: In a regional hospital, many patients are newly diagnosed with cancer. Breaking the bad news in these patients and their relatives is a tough task. Many doctors are not experienced in talking to patients about death or death-related diseases. In recent years, there have been great efforts to change the current situation. The aim of this study was to investigate the experience and education of medical personnel in breaking bad news in a secondary hospital. Materials and Methods: 59 doctors from General Hospital of Komotini, Greece were included in the study. All the doctors were in clinical specialties that treated cancer patients. A brief questionnaire was developed based on current guidelines such as Baile/SPIKES framework and the ABCDE mnemonic. Results: Residents are involved in delivering bad news less frequently than specialists. Only 21 doctors (35.59% had specific training on breaking bad news. 20 doctors (33.90% were aware of the available techniques and protocols on breaking bad news. 47 doctors (79.66% had a consistent plan for breaking bad news. 57 (96.61% delivered bad news in a quiet place, 53 (89.83% ensured no interruptions and enough time, 53 (89.83% used simple words and 54 (91.53% checked for understanding and did not rush through the news. 46 doctors (77.97% allowed relatives to determine patient′s knowledge about the disease. Conclusions: There were low rates of specific training in breaking bad news. However, the selected location, the physician′s speech and their plan were according to current guidelines.

  5. Structure-Activity Relationships and Identification of Optmized CC-Chemokine Receptor CCR1, 5, and 8 Metal-Ion Chelators

    DEFF Research Database (Denmark)

    Chalikiopoulos, Alexander; Thiele, Stefanie; Malmgaard-Clausen, Mikkel

    2013-01-01

    Chemokine receptors are involved in trafficking of leukocytes and represent targets for autoimmune conditions, inflammatory diseases, viral infections, and cancer. We recently published CCR1, CCR8, and CCR5 agonists and positive modulators based on a three metal-ion chelator series: 2,2'-bipyridine...... better accommodated in the receptors than polar groups. The new analog brominated terpyridine (29) resulted in the highest chelator potencies observed so far CCR1 (EC50: 0.49 μM) and CCR8 (EC50: 0.28 μM). Furthermore, we identified the first selective CCR5 agonist chelator, meta dithiomethylated...

  6. News search, blogs and feeds a toolkit

    CERN Document Server

    Vage, Lars

    2010-01-01

    This book is about news search and monitoring. Aimed at professionals with a strategic need of monitoring the surrounding world, users with a need to find the best news sources, monitoring services and news search strategies and techniques will benefit from reading this book. The main purpose is to present a practical handbook with an analysis of readily available tools, blending with passages of a theoretical nature. It is also useful for students at LIS programmes and related information programmes and for librarians and information professionals. The authors aim to aid the reader in reachin

  7. The news machine hacking, the untold story

    CERN Document Server

    Hanning, James

    2014-01-01

    There is one mystery figure at the heart of ?Hackergate' ? Glenn Mulcaire, the News of the World's top private investigator. The former AFC Wimbledon footballer has never spoken publicly or in court about his work investigating and backing up front-page news stories (such as the News of the World's award-winning David Beckham scoop). Mulcaire's arrest in 2006 for intercepting royal-household phone messages barely registered at the time. Yet his work has continued to generate headlines and embarrassment for the establishment ? with a Prime Minister on the back foot after his former aide Andy

  8. Association of CCR2-CCR5 haplotypes and CCL3L1 copy number with Kawasaki Disease, coronary artery lesions, and IVIG responses in Japanese children.

    Directory of Open Access Journals (Sweden)

    Manju Mamtani

    Full Text Available BACKGROUND: The etiology of Kawasaki Disease (KD is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5 and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL and response to intravenous immunoglobulin (IVIG in Japanese children, who have the highest incidence of KD, is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., four copies was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR=2.25, p=0.004 and OR=6.26, p=0.089, respectively. Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR=0.21, p=0.026 and CAL development (OR=0.44, p=0.071. CONCLUSIONS/SIGNIFICANCE: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.

  9. Healthy depictions? Depicting adoption and adoption news events on broadcast news.

    Science.gov (United States)

    Kline, Susan L; Chatterjee, Karishma; Karel, Amanda I

    2009-01-01

    Given that the public uses the media to learn about adoption as a family form, this study analyzes U.S. television news coverage of adoption between 2001 and 2005 (N = 309 stories), to identify the types of news events covered about adoption. A majority of news stories covered fraud, crime, legal disputes, and negative international adoption cases. Adoptees as defective or unhealthy were depicted more in negative news event stories, birth parents appeared less overall, and adoptive parents were most likely to have healthy depictions in positively oriented adoption experience, big family, and reunion stories. Although three quarters of the stories used primary adoption participants as news sources, one-third of the negative event stories did not contain healthy depictions of adoption participants. The authors discuss ways journalists and researchers might improve adoption news coverage.

  10. Does iris(in) bring bad news or good news?

    Science.gov (United States)

    Buscemi, Silvio; Corleo, Davide; Buscemi, Carola; Giordano, Carla

    2017-09-20

    Irisin, a novel myokine produced in response to physical activity, promotes white-to-brown fat transdifferentiation. The name irisin referred to the ancient Greek goddess Iris, the messenger who delivered (bad) news from the gods. In mice, it has been demonstrated that irisin plays a key role in metabolic regulation, energy expenditure and glucose homeostasis. New findings from various studies carried out in both animals and humans suggest that irisin might also have other favorable effects, such as increasing bone cortical mass, preventing hepatic lipid accumulation, and improving cognitive functions, thus mediating many exercise-induced health benefits. However, data on the role and function of irisin in humans have prompted controversy, due mostly to the only recent confirmation of the presence of irisin in humans. Another strong limitation to the understanding of irisin mechanisms of action is the lack of knowledge about its receptor, which until now remains unidentified in humans and in animals. This review presents an overall analysis of the history of irisin, its expression, and its involvement in health, especially in humans. Level of Evidence Level V, review.

  11. Hypertext in online news stories: More control, more appreciation

    NARCIS (Netherlands)

    Lagerwerf, L.; Verheij, D.

    2014-01-01

    News websites struggle tailoring news stories to divergent needs of online news users. We examined a way to bridge these needs by representing sources in hypertext. News items were designed to be short and concise, with hyperlinks citing sources. Readers could either ignore hyperlinks or explore

  12. 16 CFR 1012.6 - The news media.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false The news media. 1012.6 Section 1012.6... PERSONNEL AND OUTSIDE PARTIES § 1012.6 The news media. The Agency recognizes that the news media occupy a... inherently public nature of the news media allows their activities to be exempt from the requirements of this...

  13. Predicting the volume of comments on online news stories

    NARCIS (Netherlands)

    Tsagkias, M.; Weerkamp, W.; de Rijke, M.; Cheung, D.; Song, I.-Y.; Chu, W.; Hu, X.; Lin, J.; Li, J.; Peng, Z.

    2009-01-01

    On-line news agents provide commenting facilities for readers to express their views with regard to news stories. The number of user supplied comments on a news article may be indicative of its importance or impact. We report on exploratory work that predicts the comment volume of news articles

  14. The U.S. Online News Coverage of Mammography Based on a Google News Search.

    Science.gov (United States)

    Young Lin, Leng Leng; Rosenkrantz, Andrew B

    2017-12-01

    To characterize online news coverage relating to mammography, including articles' stance toward screening mammography. Google News was used to search U.S. news sites over a 9-year period (2006-2015) based on the search terms "mammography" and "mammogram." The top 100 search results were recorded. Identified articles were manually reviewed. The top 100 news articles were from the following sources: local news outlet (50%), national news outlet (24%), nonimaging medical source (13%), entertainment or culture news outlet (6%), business news outlet (4%), peer-reviewed journal (1%), and radiology news outlet (1%). Most common major themes were the screening mammography controversy (29%), description of a new breast imaging technology (23%), dense breasts (11%), and promotion of a public screening initiative (11%). For the most recent year, article stance toward screening mammography was 59%, favorable; 16%, unfavorable; and 25%, neutral. After 2010, there was an abrupt shift in articles' stances from neutral to both favorable and unfavorable. A wide range of online news sources addressed a range of issues related to mammography. National, rather than local, news sites were more likely to focus on the screening controversy and more likely to take an unfavorable view. The controversial United States Preventive Services Task Force guidelines may have influenced articles to take a stance on screening mammography. As such online news may impact public perception of the topic and thus potentially impact guideline adherence, radiologists are encouraged to maintain awareness of this online coverage and to support the online dissemination of reliable and accurate information. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Fake news. A continuation or rejection of the traditional news paradigm?

    OpenAIRE

    Palczewski, Marek

    2017-01-01

    In the article, I analysed the problem of fake news in the context of the traditional paradigm of a news story. The traditional paradigm posits that, most of all, a piece of information is true. However in contemporary media, there exist pieces of information which are fabricated and untrue. It is not a new phenomenon, yet it has intensified in recent years. News stories are fabricated for entertainment, political, or commercial purposes. They are carriers of propaganda and profit. The essenc...

  16. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J. (Veterans Administration Medical Center, Buffalo, NY (USA))

    1990-07-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

  17. Colorectal carcinoma metastases: detection with In-111-labeled monoclonal antibody CCR 086.

    Science.gov (United States)

    Abdel-Nabi, H H; Levine, G; Lamki, L M; Murray, J L; Tauxe, W N; Shah, A N; Patt, Y Z; Doerr, R J; Klein, H A; Gona, J

    1990-07-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer.

  18. Direct measurement of thermal stability of expressed CCR5 and stabilization by small molecule ligands.

    Science.gov (United States)

    Knepp, Adam M; Grunbeck, Amy; Banerjee, Sourabh; Sakmar, Thomas P; Huber, Thomas

    2011-02-01

    The inherent instability of heptahelical G protein-coupled receptors (GPCRs) during purification and reconstitution is a primary impediment to biophysical studies and to obtaining high-resolution crystal structures. New approaches to stabilizing receptors during purification and screening reconstitution procedures are needed. Here we report the development of a novel homogeneous time-resolved fluorescence assay (HTRF) to quantify properly folded CC-chemokine receptor 5 (CCR5). The assay permits high-throughput thermal stability measurements of femtomole quantities of CCR5 in detergent and in engineered nanoscale apolipoprotein-bound bilayer (NABB) particles. We show that recombinantly expressed CCR5 can be incorporated into NABB particles in high yield, resulting in greater thermal stability compared with that of CCR5 in a detergent solution. We also demonstrate that binding of CCR5 to the HIV-1 cellular entry inhibitors maraviroc, AD101, CMPD 167, and vicriviroc dramatically increases receptor stability. The HTRF assay technology reported here is applicable to other membrane proteins and could greatly facilitate structural studies of GPCRs.

  19. Design of a Base Station for MEMS CCR Localization in an Optical Sensor Network

    Directory of Open Access Journals (Sweden)

    Chan Gook Park

    2014-05-01

    Full Text Available This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC. The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR is reflected to the base station, and the Time of Flight (ToF data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR.

  20. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    International Nuclear Information System (INIS)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  1. Design of a base station for MEMS CCR localization in an optical sensor network.

    Science.gov (United States)

    Park, Chan Gook; Jeon, Hyun Cheol; Kim, Hyoun Jin; Kim, Jae Yoon

    2014-05-08

    This paper introduces a design and implementation of a base station, capable of positioning sensor nodes using an optical scheme. The base station consists of a pulse laser module, optical detectors and beam splitter, which are mounted on a rotation-stage, and a Time to Digital Converter (TDC). The optical pulse signal transmitted to the sensor node with a Corner Cube Retro-reflector (CCR) is reflected to the base station, and the Time of Flight (ToF) data can be obtained from the two detectors. With the angle and flight time data, the position of the sensor node can be calculated. The performance of the system is evaluated by using a commercial CCR. The sensor nodes are placed at different angles from the base station and scanned using the laser. We analyze the node position error caused by the rotation and propose error compensation methods, namely the outlier sample exception and decreasing the confidence factor steadily using the recursive least square (RLS) methods. Based on the commercial CCR results, the MEMS CCR is also tested to demonstrate the compatibility between the base station and the proposed methods. The result shows that the localization performance of the system can be enhanced with the proposed compensation method using the MEMS CCR.

  2. Influence of CCR7 ligand DNA preexposure on the magnitude and duration of immunity

    International Nuclear Information System (INIS)

    Lee, Yunsang; Seong, Kug Eo; Rouse, Richard J.D.; Rouse, Barry T.

    2003-01-01

    The CC chemokine receptor (CCR) 7 ligands CCL21 and CCL19 were recently described as essential elements for establishing the microenvironment needed to initiate optimal immune responses in secondary lymphoid tissues. In the present study we have kinetically investigated the primary responses of naive DO11.10 TCR-transgenic CD4+ T cells (OVA323-339 peptide specific) adoptively transferred into normal BALB/c mice given plasmid DNA encoding CCR7 ligands. The primary responses of CD4+ Tg-T cells in CCR7 ligand DNA recipients occurred more promptly, reaching levels higher than those observed in vector controls. In line with enhanced specific immunity, the T-cell population in CCR7 ligand recipients underwent more in vivo cell division following Ag stimulation, and a higher percentage of Ag-specific T cells expressed an activation phenotype. Moreover, the enhanced primary responses of naive CD4+ T cells appeared to act via affects on migration and maturation of CD11c+ dendritic cells in the draining lymph nodes. In addition following mucosal challenge of herpes simplex virus-immune mice with virus, those that had received CCL21 or CCL19 during priming contained a higher frequency of responding CD4 T cells in lymph nodes and the site of infection. Moreover, CCL21- and CCL19-treated mice showed less severe disease and better survival following challenge. Our results are discussed in terms of the relevance of CCR7 ligand preimmunization to improve vaccine

  3. Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis.

    Directory of Open Access Journals (Sweden)

    Urs B Hagemann

    Full Text Available CC chemokine receptor 4 (CCR4 represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs and on tumor cells in several cancer types and its role in metastasis.Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the newly selected anti-CCR4 antibodies.For the first time, successful generation of anti- G-protein coupled chemokine receptor (GPCR antibodies using human non-immune library and phage display on GPCR-expressing cells was demonstrated. The generated anti-CCR4 antibodies possess a dual mode of action (inhibition of ligand-induced signaling and antibody-directed tumor cell killing. The data demonstrate that the anti-tumor activity in vivo is mediated, at least in part, through Fc-receptor dependent effector mechanisms, such as ADCC and phagocytosis. Anti-CC chemokine receptor 4 antibodies inhibiting receptor signaling have potential as immunomodulatory antibodies for cancer.

  4. Inhibition of HIV-1 infection by synthetic peptides derived CCR5 fragments

    International Nuclear Information System (INIS)

    Imai, Masaki; Baranyi, Lajos; Okada, Noriko; Okada, Hidechika

    2007-01-01

    HIV-1 infection requires interaction of viral envelope protein gp160 with CD4 and a chemokine receptor, CCR5 or CXCR4 as entry coreceptor. We designed HIV-inhibitory peptides targeted to CCR5 using a novel computer program (ANTIS), which searched all possible sense-antisense amino acid pairs between proteins. Seven AHBs were found in CCR5 receptor. All AHB peptides were synthesized and tested for their ability to prevent HIV-1 infection to human T cells. A peptide fragment (LC5) which is a part of the CCR5 receptor corresponding to the loop between the fifth and sixth transmembrane regions (amino acids 222-240) proved to inhibit HIV-1 IIIB infection of MT-4 cells. Interaction of these antisense peptides could be involved in sustaining HIV-1 infectivity. LC5 effectively indicated dose-dependent manner, and the suppression was enhanced additively by T20 peptide, which inhibits infection in vitro by disrupting the gp41 conformational changes necessary for membrane fusion. Thus, these results indicate that CCR5-derived AHB peptides could provide a useful tool to define the mechanism(s) of HIV infection, and may provide insight which will contribute to the development of an anti-HIV-1 reagent

  5. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

    Science.gov (United States)

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

    2014-01-09

    Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

  6. CCR5 polymorphism and plague resistance in natural populations of the black rat in Madagascar.

    Science.gov (United States)

    Tollenaere, C; Rahalison, L; Ranjalahy, M; Rahelinirina, S; Duplantier, J-M; Brouat, C

    2008-12-01

    Madagascar remains one of the world's largest plague foci. The black rat, Rattus rattus, is the main reservoir of plague in rural areas. This species is highly susceptible to plague in plague-free areas (low-altitude regions), whereas rats from the plague focus areas (central highlands) have evolved a disease-resistance polymorphism. We used the candidate gene CCR5 to investigate the genetic basis of plague resistance in R. rattus. We found a unique non-synonymous substitution (H184R) in a functionally important region of the gene. We then compared (i) CCR5 genotypes of dying and surviving plague-challenged rats and (ii) CCR5 allelic frequencies in plague focus and plague-free populations. Our results suggested a higher prevalence of the substitution in resistant animals compared to susceptible individuals, and a tendency for higher frequencies in plague focus areas compared to plague-free areas. Therefore, the CCR5 polymorphism may be involved in Malagasy black rat plague resistance. CCR5 and other undetermined plague resistance markers may provide useful biological information about host evolution and disease dynamics.

  7. Preventing HIV transmission through blockade of CCR5: rationale, progress and perspectives.

    Science.gov (United States)

    Hartley, Oliver; Martins, Elsa; Scurci, Ilaria

    2018-01-29

    Of the two million people estimated to be newly infected with human immunodeficiency virus (HIV) every year, 95% live in poorer regions of the world where effective HIV treatment is not universally available. Strategies to reduce the spread of HIV infection, which predominantly occurs via sexual contact, are urgently required. In the absence of an effective vaccine, a number of approaches to prevent HIV infection have been developed. These include using potent anti-HIV drugs prophylactically, either through systemic administration or topical application to the mucosal tissues that HIV initially encounters during sexual transmission. Genetic deficiency of the chemokine receptor CCR5 provides individuals with a remarkable degree of protection from HIV acquisition. This is because CCR5 is the major coreceptor used by HIV to infect new target cells. Since CCR5 deficiency does not appear to carry any health disadvantages, targeting the receptor is a promising strategy for both therapy and prevention of HIV. In this review we first describe the advantages and limitations of the currently available strategies for HIV prevention, then we focus on strategies targeting CCR5, covering the progress that has been made in developing different classes of CCR5 inhibitors for prophylaxis, and the perspectives for their future development as new weapons in the global fight against HIV/AIDS.

  8. Incorporating popularity in a personalized news recommender system

    Directory of Open Access Journals (Sweden)

    Nirmal Jonnalagedda

    2016-06-01

    Full Text Available Online news reading has become a widely popular way to read news articles from news sources around the globe. With the enormous amount of news articles available, users are easily overwhelmed by information of little interest to them. News recommender systems help users manage this flood by recommending articles based on user interests rather than presenting articles in order of their occurrence. We present our research on developing personalized news recommendation system with the help of a popular micro-blogging service, “Twitter.” News articles are ranked based on the popularity of the article identified from Twitter’s public timeline. In addition, users construct profiles based on their interests and news articles are also ranked based on their match to the user profile. By integrating these two approaches, we present a hybrid news recommendation model that recommends interesting news articles to the user based on their popularity as well as their relevance to the user profile.

  9. INVISIBLE GIANTS IN BROADCAST JOURNALISM: news agencies and the global news ecosystem

    Directory of Open Access Journals (Sweden)

    Maria Cleidejane Esperidião

    2011-06-01

    Full Text Available Key actors of the global informational web, the international television news agencies are not often covered in the communications field in Brazil. This paper aims to understand the dynamics established between these transnational companies and their subscribers (world television stations. It attempts to clarify how these western-led news agency companies operate within the flow of communication. It intends to identify production processes (assessment, collection, treatment and radial distribution for the Associated Press Television News (APTN and Reuters Television News (Reuters TV.

  10. Invisible giants in broadcast journalism: news agencies and the global news ecosystem

    Directory of Open Access Journals (Sweden)

    Maria Cleidejane Esperidião

    2011-06-01

    Full Text Available Key actors of the global informational web, the international television news agencies are not often covered in the communications field in Brazil. This paper aims to understand the dynamics established between these transnational companies and their subscribers (world television stations. It attempts to clarify how these western-led news agency companies operate within the flow of communication. It intends to identify production processes (assessment, collection, treatment and radial distribution for the Associated Press Television News (APTN and Reuters Television News (Reuters TV.

  11. Benefits and Pitfalls: Producing TV News

    Science.gov (United States)

    Watters, Laura

    1974-01-01

    Examines the live television news show produced by students and faculty at Northern Illinois University with the aim of helping others avoid some difficulties and frustrations when setting up a similar show in their journalism curriculum. (TO)

  12. Uncovering the skewness news impact curve

    Czech Academy of Sciences Publication Activity Database

    Anatolyev, Stanislav; Petukhov, A.

    2016-01-01

    Roč. 14, č. 4 (2016), s. 746-771 ISSN 1479-8409 Institutional support: RVO:67985998 Keywords : conditional skewness * news impact curve * stock returns Subject RIV: AH - Economics Impact factor: 1.800, year: 2016

  13. Nuclear Malaysia in the news 2010

    International Nuclear Information System (INIS)

    2011-01-01

    Nuclear was a term that always misunderstood by public as a terrifying term. Nuclear activities around Malaysia were disseminated in newspaper and Malaysian Nuclear Agency as a responsible agency were collecting that news and compiled them. The purpose for this compilation were to make the public aware the benefits of nuclear energy and all the activities regarding nuclear surround them. All the news about nuclear technology were collected using various type of newspaper published in Malaysia such as Utusan Malaysia, Berita Harian, Daily Express, News Straits Time, The Star, Borneo Post and others. This news was compiled according to their main topics such as energy, nuclear in agriculture, education and others. Each year one edition of this report will publish and disseminate it to the other libraries, government agencies, school and others to make the public aware the existence of nuclear activities around their countries.

  14. Alternative Fuel News, Vol. 3 No. 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-09-23

    This special issue of Alternative Fuel News highlights the Fifth National Clean Cities Conference held in Louisville, Kentucky. The momentum for the program is stronger than ever and the coalitions are working to propel the alternative fuel industry forward.

  15. Alternative Fuel News, Volume 4, Number 3

    Energy Technology Data Exchange (ETDEWEB)

    Ficker, C.

    2000-11-14

    This issue of Alternative Fuel News focuses on transit buses and refuse haulers. Many transit agencies and waste management companies are investigating alternatives to traditional diesel buses and refuse haulers.

  16. Nuclear Malaysia in the news 2011

    International Nuclear Information System (INIS)

    2012-01-01

    Nuclear was a term that always misunderstood by public as a terrifying term. Nuclear activities around Malaysia were disseminated in newspaper and Malaysian Nuclear Agency as a responsible agency were collecting that news and compiled them. The purpose for this compilation were to make the public aware the benefits of nuclear energy and all the activities regarding nuclear surround them. All the news about nuclear technology were collected using various type of newspaper published in Malaysia such as Utusan Malaysia, Berita Harian, Daily Express, News Straits Time, The Star, Borneo Post and others. This news was compiled according to their main topics such as energy, nuclear in agriculture, education and others. Each year one edition of this report will publish and disseminate it to the other libraries, government agencies, school and others to make the public aware the existence of nuclear activities around their countries.

  17. Communicating Uncertain News in Cancer Consultations.

    Science.gov (United States)

    Alby, Francesca; Zucchermaglio, Cristina; Fatigante, Marilena

    2017-12-01

    In cancer communication, most of the literature is in the realm of delivering bad news while much less attention has been given to the communication of uncertain news around the diagnosis and the possible outcomes of the illness. Drawing on video-recorded cancer consultations collected in two Italian hospitals, this article analyzes three communication practices used by oncologists to interactionally manage the uncertainty during the visit: alternating between uncertain bad news and certain good news, anticipating scenarios, and guessing test results. Both diagnostic and personal uncertainties are not hidden to the patient, yet they are reduced through these practices. Such communication practices are present in 32 % of the visits in the data set, indicating that the interactional management of uncertainty is a relevant phenomenon in oncological encounters. Further studies are needed to improve both its understanding and its teaching.

  18. The Spatiotemporal Dynamics of Digital News Audiences

    DEFF Research Database (Denmark)

    Peters, Chris

    2016-01-01

    The changing patterns of news consumption in a digital era bring about new configurations between audiences, information, the devices upon which they consume it and the different (mobile) places and (shiftable) times where and when this is possible. This chapter highlights the need to consider...... these interrelated changes in the media ecology if we want to grasp the newfound complexity of media consumption. Specifically, it outlines how audience engagement with news and different spatiotemporal configurations made possible by digital technology are trends that complement and reinforce one another in terms...... of changing the socially-situated affordances of news use. Having sketched these contours, the chapter then highlights analytical challenges for understanding and conceptualizing the new interrelations between digital news content, production, and consumption, grounding this analysis with theoretical insights...

  19. News Media Framing of Negative Campaigning

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2014-01-01

    News media coverage of election campaigns is often characterized by use of the strategic game frame and a focus on politicians’ use of negative campaigning. However, the exact relationship between these two characteristics of news coverage is largely unexplored. This article theorizes that consumer...... demand and norms of journalistic independence might induce the news media outlets to cover negative campaigning with a strategic game frame. A comprehensive content analysis based on several newspaper types, several election campaigns, and several different measurements of media framing confirms...... that news coverage of negative campaigning does apply the strategic game frame to a significantly larger degree than articles covering positive campaigning. This finding has significant implications for campaigning politicians and for scholars studying campaign and media effects....

  20. Nuclear Malaysia in The News 2015

    International Nuclear Information System (INIS)

    2016-01-01

    Nuclear was a term that always misunderstands by public as a terrifying term. The nuclear activities around Malaysia was disseminated in newspaper and Malaysian Nuclear Agency as a responsible agency for nuclear for peace were collecting that news and compiled them to make the public aware the benefits of nuclear energy to develop our country. All the news about nuclear were collected using various type of newspaper published in Malaysia such as Utusan Malaysia, Berita Harian, Daily Express, News Straits Time, The Star, Borneo Post and others. This news was compiled according to their main topics such as energy, nuclear in agriculture, education and others. Each year one edition of this report will publish and disseminate it to the other libraries, government agencies, school and others to make the public aware the existence of nuclear activities around their countries.

  1. The Electronic Archiving of Arab News Agencies

    Directory of Open Access Journals (Sweden)

    Haifa Ayub Gigawy

    2007-03-01

    Full Text Available This Research aims to present the electronic archives of Arab news agency websites and their methods of searching for and retrieving information. Also, its aim is to examine all their methods in order to find out which are the best and most practically useful ones. The research refers to the news agencies and the Internet, through the methods that users encounter in these inquires and links which present information. It concentrates on practical ways of searching for news items in both texts and pictures. The research contains tables showing the results. It presents a brief summery for each of Arab news agencies.The research comes to the conclusion that there are many things which need to be considered, and also some suggestions as to how the search for and retrieval of information might be improved

  2. Uncovering the skewness news impact curve

    Czech Academy of Sciences Publication Activity Database

    Anatolyev, Stanislav; Petukhov, A.

    2016-01-01

    Roč. 14, č. 4 (2016), s. 746-771 ISSN 1479-8409 Institutional support: PRVOUK-P23 Keywords : conditional skewness * news impact curve * stock returns Subject RIV: AH - Economics Impact factor: 1.800, year: 2016

  3. Nuclear Malaysia in the news 2012

    International Nuclear Information System (INIS)

    2013-01-01

    Nuclear was a term that always misunderstood by public as a terrifying term. Nuclear activities around Malaysia were disseminated in newspaper and Malaysian Nuclear Agency as a responsible agency were collecting that news and compiled them. The purpose for this compilation were to make the public aware the benefits of nuclear energy and all the activities regarding nuclear surround them. All the news about nuclear technology were collected using various type of newspaper published in Malaysia such as Utusan Malaysia, Berita Harian, Daily Express, News Straits Time, The Star, Borneo Post and others. This news was compiled according to their main topics such as energy, nuclear in agriculture, education and others. Each year one edition of this report will publish and disseminate it to the other libraries, government agencies, school and others to make the public aware the existence of nuclear activities around their countries.

  4. Nuclear Malaysia in the news 2008

    International Nuclear Information System (INIS)

    2009-01-01

    Nuclear was a term that always misunderstood by public as a terrifying term. Nuclear activities around Malaysia were disseminated in newspaper and Malaysian Nuclear Agency as a responsible agency were collecting that news and compiled them. The purpose for this compilation were to make the public aware the benefits of nuclear energy and all the activities regarding nuclear surround them. All the news about nuclear technology were collected using various type of newspaper published in Malaysia such as Utusan Malaysia, Berita Harian, Daily Express, News Straits Time, The Star, Borneo Post and others. This news was compiled according to their main topics such as energy, nuclear in agriculture, education and others. Each year one edition of this report will publish and disseminate it to the other libraries, government agencies, school and others to make the public aware the existence of nuclear activities around their countries.

  5. Nuclear Malaysia in the news 2014

    International Nuclear Information System (INIS)

    2009-01-01

    Nuclear was a term that always misunderstands by public as a terrifying term. The nuclear activities around Malaysia was disseminated in newspaper and Malaysian Nuclear Agency as a responsible agency for nuclear for peace were collecting that news and compiled them to make the public aware the benefits of nuclear energy to develop our country. All the news about nuclear were collected using various type of newspaper published in Malaysia such as Utusan Malaysia, Berita Harian, Daily Express, News Straits Time, The Star, Borneo Post and others. This news was compiled according to their main topics such as energy, nuclear in agriculture, education and others. Each year one edition of this report will publish and disseminate it to the other libraries, government agencies, school and others to make the public aware the existence of nuclear activities around their countries.

  6. Murine macrophage response from peritoneal cavity requires signals mediated by chemokine receptor CCR-2 during Staphylococcus aureus infection.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2016-02-01

    C-C chemokine receptor-2 (CCR-2) is a cognate receptor for monocyte chemotactic protein-1 (MCP-1), and recent studies revealed that MCP-1-CCR-2 signaling is involved in several inflammatory diseases characterized by macrophage infiltration. Currently, there is no study on the involvement of CCR-2 in the killing of S. aureus by macrophages of Swiss albino mice, and its substantial role in host defense against S. aureus infection in murine macrophages is still unclear. Therefore, the present study was aimed to investigate the functional and interactive role of CCR-2 and MCP-1 in regulating peritoneal macrophage responses with respect to acute S. aureus infection. We found that phagocytosis of S. aureus can serve as an important stimulus for MCP-1 production by peritoneal macrophages, which is dependent directly or indirectly on cytokines, reactive oxygen species and nitric oxide. Neutralization of CCR-2 in macrophages leads to increased production of IL-10 and decreased production of IFN-γ and IL-6. In CCR-2 blocked macrophages, pretreatment with specific blocker of NF-κB or p38-MAPK causes elevation in MCP-1 level and subsequent downregulation of CCR-2 itself. We speculate that CCR-2 is involved in S. aureus-induced MCP-1 production via NF-κB or p38-MAPK signaling. We also hypothesized that unnaturally high level of MCP-1 that build up upon CCR-2 neutralization might allow promiscuous binding to one or more other chemokine receptors, a situation that would not occur in CCR-2 non-neutralized condition. This may be the plausible explanation for such observed Th-2 response in CCR-2 blocked macrophages infected with S. aureus in the present study.

  7. A test of rivaling approaches to explain news effects: A multi-wave panel study of agenda setting, social and economic conditions, the tone of the news, and horse race news

    NARCIS (Netherlands)

    Kleinnijenhuis, J.; van Hoof, A.M.J.; Oegema, D.; de Ridder, J.A.

    2007-01-01

    Different "paradigmatic" approaches to explain news effects on voting may supplement each other, because their starting points are based on different news types in political campaign news: news on issue positions of parties, news on real-world developments, news on support or criticism for parties,

  8. News media consumption among immigrants in Europe

    DEFF Research Database (Denmark)

    Christiansen, Connie Carøe

    2004-01-01

    In recent years, especially with the advent of Digital Broadcasting Technology, transnational media has become central in the consumption of news by immigrant populations. This has received some attention as a factor associated with lack of integration into their new societies. The present article...... international news than is currently the national television channels, are also part of the picture. A diaspora perspective transforms the prospect presented by observers and journalists, worried about integration processes, and prompts considerations that immigrants are also emigrants....

  9. Media bias, news customization and competition

    OpenAIRE

    Pires, Armando José Garcia

    2010-01-01

    The media bias literature has focused its attention on single-ideology media firms. We analyze the incentives for media firms to adopt a multi-ideology strategy. A multi-ideology strategy occurs when a media firm adapts news to consumers’ political preferences. In this sense, news customization can reduce media bias, since media firms can cover a larger variety of political opinions. We show that although the incentives to customize are larger under duopoly than under monopoly, a monopolist m...

  10. CERN Video News, 2nd edition

    CERN Multimedia

    2002-01-01

    This week you will be able to watch on the web the second edition of CERN's video news (see Bulletin n°45/2002, p.3). On this news reel: the ATRAP experiment's latest achievements, superconducting cable production for CMS, the CAST experiment and the European digital conferencing project InDiCo. Go to : www.cern.ch/video, or Bulletin web page.

  11. Collective action, clientelism and connectivity

    DEFF Research Database (Denmark)

    Shami, Mahvish

    action studies, however, is that collective action will often break down under hierarchical social relationships. This is unfortunate news for rural societies in developing countries, as these are often entrenched in patron-client networks. And while studies of collective action under clientelism...... that the unequal relationship between landlords and peasants does not, in and by itself, block peasant collective action. Rather, it is the interaction between clientelism and isolation that allow patrons to block community based projects. Despite still relying on powerful landlords, peasants in connected villages...

  12. CCR5 antibodies HGS004 and HGS101 preferentially inhibit drug-bound CCR5 infection and restore drug sensitivity of Maraviroc-resistant HIV-1 in primary cells

    International Nuclear Information System (INIS)

    Latinovic, Olga; Reitz, Marvin; Le, Nhut M.; Foulke, James S.; Faetkenheuer, Gerd; Lehmann, Clara; Redfield, Robert R.; Heredia, Alonso

    2011-01-01

    R5 HIV-1 strains resistant to the CCR5 antagonist Maraviroc (MVC) can use drug-bound CCR5. We demonstrate that MVC-resistant HIV-1 exhibits delayed kinetics of coreceptor engagement and fusion during drug-bound versus free CCR5 infection of cell lines. Antibodies directed against the second extracellular loop (ECL2) of CCR5 had greater antiviral activity against MVC-bound compared to MVC-free CCR5 infection. However, in PBMCs, only ECL2 CCR5 antibodies HGS004 and HGS101, but not 2D7, inhibited infection by MVC resistant HIV-1 more potently with MVC-bound than with free CCR5. In addition, HGS004 and HGS101, but not 2D7, restored the antiviral activity of MVC against resistant virus in PBMCs. In flow cytometric studies, CCR5 binding by the HGS mAbs, but not by 2D7, was increased when PBMCs were treated with MVC, suggesting MVC increases exposure of the relevant epitope. Thus, HGS004 and HGS101 have antiviral mechanisms distinct from 2D7 and could help overcome MVC resistance.

  13. HIV-1 adaptation to low levels of CCR5 results in V3 and V2 loop changes that increase envelope pathogenicity, CCR5 affinity and decrease susceptibility to Maraviroc.

    Science.gov (United States)

    Garg, Himanshu; Lee, Raphael T C; Maurer-Stroh, Sebastian; Joshi, Anjali

    2016-06-01

    Variability in CCR5 levels in the human population is suggested to affect virus evolution, fitness and the course of HIV disease. We previously demonstrated that cell surface CCR5 levels directly affect HIV Envelope mediated bystander apoptosis. In this study, we attempted to understand HIV evolution in the presence of low levels of CCR5, mimicking the limiting CCR5 levels inherent to the host. HIV-1 adaptation in a T cell line expressing low levels of CCR5 resulted in two specific mutations; N302Y and E172K. The N302Y mutation led to accelerated virus replication, increase in Maraviroc IC50 and an increase in Envelope mediated bystander apoptosis in low CCR5 expressing cells. Analysis of subtype B sequences showed that N302Y is over-represented in CXCR4 tropic viruses in comparison to CCR5 tropic isolates. Considering the variability in CCR5 levels between individuals, our findings have implications for virus evolution, MVC susceptibility as well as HIV pathogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. CCR5 antibodies HGS004 and HGS101 preferentially inhibit drug-bound CCR5 infection and restore drug sensitivity of Maraviroc-resistant HIV-1 in primary cells

    Science.gov (United States)

    Latinovic, Olga; Reitz, Marvin; Le, Nhut M.; Foulke, James S.; Fätkenheuer, Gerd; Lehmann, Clara; Redfield, Robert R.; Heredia, Alonso

    2010-01-01

    R5 HIV-1 strains resistant to the CCR5 antagonist Maraviroc (MVC) can use drug-bound CCR5. We demonstrate that MVC-resistant HIV-1 exhibits delayed kinetics of coreceptor engagement and fusion during drug-bound versus free CCR5 infection of cell lines. Antibodies directed against the second extracellular loop (ECL2) of CCR5 had greater antiviral activity against MVC-bound compared to MVC-free CCR5 infection. However, in PBMCs, only ECL2 CCR5 antibodies HGS004 and HGS101, but not 2D7, inhibited infection by MVC resistant HIV-1 more potently with MVC-bound than with free CCR5. In addition, HGS004 and HGS101, but not 2D7, restored the antiviral activity of MVC against resistant virus in PBMCs. In flow cytometric studies, CCR5 binding by the HGS mAbs, but not by 2D7, was increased when PBMCs were treated with MVC, suggesting MVC increases exposure of the relevant epitope. Thus, HGS004 and HGS101 have antiviral mechanisms distinct from 2D7 and could help overcome MVC resistance. PMID:21232779

  15. No evidence for an effect of the CCR5 delta32/+ and CCR2b 64I/+ mutations on human immunodeficiency virus (HIV)-1 disease progression among HIV-1-infected injecting drug users

    NARCIS (Netherlands)

    Schinkel, J.; Langendam, M. W.; Coutinho, R. A.; Krol, A.; Brouwer, M.; Schuitemaker, H.

    1999-01-01

    The relationship between CCR5 and CCR2b genotypes and human immunodeficiency virus (HIV)-1 disease progression was studied among the 108 seroconverters of the Amsterdam cohort of injecting drug users (IDUs). In contrast to earlier studies among homosexual men, no effect on disease progression of the

  16. 'BREAKS' Protocol for Breaking Bad News.

    Science.gov (United States)

    Narayanan, Vijayakumar; Bista, Bibek; Koshy, Cheriyan

    2010-05-01

    Information that drastically alters the life world of the patient is termed as bad news. Conveying bad news is a skilled communication, and not at all easy. The amount of truth to be disclosed is subjective. A properly structured and well-orchestrated communication has a positive therapeutic effect. This is a process of negotiation between patient and physician, but physicians often find it difficult due to many reasons. They feel incompetent and are afraid of unleashing a negative reaction from the patient or their relatives. The physician is reminded of his or her own vulnerability to terminal illness, and find themselves powerless over emotional distress. Lack of sufficient training in breaking bad news is a handicap to most physicians and health care workers. Adherence to the principles of client-centered counseling is helpful in attaining this skill. Fundamental insight of the patient is exploited and the bad news is delivered in a structured manner, because the patient is the one who knows what is hurting him most and he is the one who knows how to move forward. Six-step SPIKES protocol is widely used for breaking bad news. In this paper, we put forward another six-step protocol, the BREAKS protocol as a systematic and easy communication strategy for breaking bad news. Development of competence in dealing with difficult situations has positive therapeutic outcome and is a professionally satisfying one.

  17. Breaking bad news: the patient's viewpoint.

    Science.gov (United States)

    Munoz Sastre, Maria Teresa; Sorum, Paul Clay; Mullet, Etienne

    2011-10-01

    The objective of this study was to ascertain how patients judge the acceptability of physicians' communication of bad news. Two hundred forty-five adults, who had in the past received bad medical news, indicated the acceptability of physicians' conduct in 48 vignettes of giving bad news to patients. Vignettes were all combinations of five factors: level of bad news (infection with hepatitis C, cirrhosis of the liver, or liver cancer); request or not to the patient to come with spouse or partner; attempt or not by the physician to find out the patient's expectations about the test results; presence or absence of emotional supportiveness; and provision or not of complete and understandable information. In addition, nine physicians rated the same vignettes. Quality of information and emotional supportiveness explained more than 95% of the variance in patients' acceptability judgments, while the degree of badness of the news had no impact. In addition, for patients, low emotional supportiveness could not be fully compensated by high quality of information, nor the inverse. Physicians, in contrast, responded as if such compensations were possible. Physicians must appreciate that patients expect high levels of both empathy and information quality, no matter how bad the news.

  18. Giving Bad News: A Qualitative Research Exploration

    Science.gov (United States)

    Aein, Fereshteh; Delaram, Masoumeh

    2014-01-01

    Background: The manner in which healthcare professionals deliver bad news affects the way it is received, interpreted, understood, and dealt with. Despite the fact that clinicians are responsible for breaking bad news, it has been shown that they lack skills necessary to perform this task. Objectives: The purpose of this study was to explore Iranian mothers’ experiences to receive bad news about their children cancer and to summarize suggestions for improving delivering bad news by healthcare providers. Materials and Methods: A qualitative approach using content analysis was adopted. Semi-structured interviews were conducted with 14 mothers from two pediatric hospitals in Iran. Results: Five major categories emerged from the data analysis, including dumping information, shock and upset, emotional work, burden of delivering bad news to the family members, and a room for multidisciplinary approach. Conclusions: Effective communication of healthcare team with mothers is required during breaking bad news. Using multidisciplinary approaches to prevent harmful reactions and providing appropriate support are recommended. PMID:25068066

  19. News from the gas world

    International Nuclear Information System (INIS)

    Gadonneix, P.; Bergmann, B.; Chabrelie, M.F.

    2000-01-01

    Mr Pierre Gadonneix, President of Gaz de France, presented 'The Gaz de France Group in the new European context: opportunities and strategy of a major gas operator' during the 21. world gas congress, which was held in Nice from 6. to 9. June 2000. A few weeks from the liberalization of the gas market in Europe. It seems interesting to publish this article, which very pertinently presents the point of view of the leading French gas operator. We also considered it right to publish the presentation of Mr Burckhard Bergmann, President of Eurogas, who presented the European vision. To complete this panorama of the gas situation, we are also publishing news about the international gas situation in 1999, written by Marie-Francoise Chabrelie of Cedigaz which is summarized here under: in a changing environment, characterized by privatisation, the deregulation and the opening up of markets (Europe, Australia), natural gas has progressively gained ground in the world energy market. This trend was confirmed in 1999. Major discoveries open the way to new projects for local use and export. In spite of the uncertainties regarding the situation in countries of the ex-Soviet Union, several favourable factors, including economic recovery in Asia faster than forecast, indicate a growth hypothesis ranging from 2.5% for this year. (authors)

  20. Top medical news stories 2015

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2015-12-01

    Full Text Available No abstract available. Article truncated after 150 words. Here is our list of the top seven medical news stories for 2015 with special emphasis on the Southwest. 7. Wearable health devices: A wave of wearable computing devices such as Fitbit and UP wristbands have people keeping track of how much they sit, stand, walk, climb stairs and calories they consume (1. These fitness-tracking devices herald a series of devices that will detect and monitor serious diseases. However, these so-called medical-grade wearables require approval from the U.S. Food and Drug Administration, a regulatory hurdle avoided by the fitness-tracking devices which will likely slow their introduction. 6. Caitlyn Jenner: Caitlyn Jenner became the most famous transgender woman in the world following an interview published in Vanity Fair (2. The Vanity Fair website saw 11.6 million visits curious about the former Olympic athlete. Though Jenner publicly shared her gender identity, many transgender Americans do not-12% of gender non-conforming adults said they ...

  1. Resistance to the CCR5 inhibitor 5P12-RANTES requires a difficult evolution from CCR5 to CXCR4 coreceptor use.

    Directory of Open Access Journals (Sweden)

    Rebecca Nedellec

    Full Text Available Viral resistance to small molecule allosteric inhibitors of CCR5 is well documented, and involves either selection of preexisting CXCR4-using HIV-1 variants or envelope sequence evolution to use inhibitor-bound CCR5 for entry. Resistance to macromolecular CCR5 inhibitors has been more difficult to demonstrate, although selection of CXCR4-using variants might be expected. We have compared the in vitro selection of HIV-1 CC1/85 variants resistant to either the small molecule inhibitor maraviroc (MVC or the macromolecular inhibitor 5P12-RANTES. High level resistance to MVC was conferred by the same envelope mutations as previously reported after 16-18 weeks of selection by increasing levels of MVC. The MVC-resistant mutants were fully sensitive to inhibition by 5P12-RANTES. By contrast, only transient and low level resistance to 5P12-RANTES was achieved in three sequential selection experiments, and each resulted in a subsequent collapse of virus replication. A fourth round of selection by 5P12-RANTES led, after 36 weeks, to a "resistant" variant that had switched from CCR5 to CXCR4 as a coreceptor. Envelope sequences diverged by 3.8% during selection of the 5P12-RANTES resistant, CXCR4-using variants, with unique and critical substitutions in the V3 region. A subset of viruses recovered from control cultures after 44 weeks of passage in the absence of inhibitors also evolved to use CXCR4, although with fewer and different envelope mutations. Control cultures contained both viruses that evolved to use CXCR4 by deleting four amino acids in V3, and others that maintained entry via CCR5. These results suggest that coreceptor switching may be the only route to resistance for compounds like 5P12-RANTES. This pathway requires more mutations and encounters more fitness obstacles than development of resistance to MVC, confirming the clinical observations that resistance to small molecule CCR5 inhibitors very rarely involves coreceptor switching.

  2. Insights into the structure and architecture of the CCR4-NOT complex.

    Science.gov (United States)

    Xu, Kun; Bai, Yuwei; Zhang, Aili; Zhang, Qionglin; Bartlam, Mark G

    2014-01-01

    The CCR4-NOT complex is a highly conserved, multifunctional machinery with a general role in controlling mRNA metabolism. It has been implicated in a number of different aspects of mRNA and protein expression, including mRNA degradation, transcription initiation and elongation, ubiquitination, and protein modification. The core CCR4-NOT complex is evolutionarily conserved and consists of at least three NOT proteins and two catalytic subunits. The L-shaped complex is characterized by two functional modules bound to the CNOT1/Not1 scaffold protein: the deadenylase or nuclease module containing two enzymes required for deadenylation, and the NOT module. In this review, we will summarize the currently available information regarding the three-dimensional structure and assembly of the CCR4-NOT complex, in order to provide insight into its roles in mRNA degradation and other biological processes.

  3. Insights into the structure and architecture of the CCR4–NOT complex

    Science.gov (United States)

    Xu, Kun; Bai, Yuwei; Zhang, Aili; Zhang, Qionglin; Bartlam, Mark G.

    2014-01-01

    The CCR4–NOT complex is a highly conserved, multifunctional machinery with a general role in controlling mRNA metabolism. It has been implicated in a number of different aspects of mRNA and protein expression, including mRNA degradation, transcription initiation and elongation, ubiquitination, and protein modification. The core CCR4–NOT complex is evolutionarily conserved and consists of at least three NOT proteins and two catalytic subunits. The L-shaped complex is characterized by two functional modules bound to the CNOT1/Not1 scaffold protein: the deadenylase or nuclease module containing two enzymes required for deadenylation, and the NOT module. In this review, we will summarize the currently available information regarding the three-dimensional structure and assembly of the CCR4–NOT complex, in order to provide insight into its roles in mRNA degradation and other biological processes. PMID:24904637

  4. Molecular interaction of a potent nonpeptide agonist with the chemokine receptor CCR8

    DEFF Research Database (Denmark)

    Jensen, Pia C; Nygaard, Rie; Thiele, Stefanie

    2007-01-01

    Most nonpeptide antagonists for CC-chemokine receptors share a common pharmacophore with a centrally located, positively charged amine that interacts with the highly conserved glutamic acid (Glu) located in position 6 of transmembrane helix VII (VII:06). We present a novel CCR8 nonpeptide agonist......, 8-[3-(2-methoxyphenoxy)benzyl]-1-phenethyl-1,3,8-triaza-spiro[4.5]decan-4-one (LMD-009), that also contains a centrally located, positively charged amine. LMD-009 selectively stimulated CCR8 among the 20 identified human chemokine receptors. It mediated chemotaxis, inositol phosphate accumulation......-binding pockets of CCR8 uncovered that the binding of LMD-009 and of four analogs [2-(1-(3-(2-methoxyphenoxy)benzyl)-4-hydroxypiperidin-4-yl)benzoic acid (LMD-584), N-ethyl-2-4-methoxybenzenesulfonamide (LMD-902), N-(1-(3-(2-methoxyphenoxy)benzyl)piperidin-4-yl)-2-phenyl-4-(pyrrolidin-1yl)butanamide (LMD-268...

  5. Characterization of developmental and stress mediated expression of cinnamoyl-CoA reductase (CCR) in kenaf (Hibiscus cannabinus L.)

    Science.gov (United States)

    Cinnamoyl-CoA reductase (CCR) is an important enzyme for lignin biosynthesis as it catalyzes the first specific committed step in monolignol biosynthesis. We have cloned a full length coding sequence of CCR from kenaf (Hibiscus cannabinus L.), which contains a 1,020-bp open reading frame (ORF), enco...

  6. DOWN-REGULATION OF CINNAMOYL-COA REDUCTASE (CCR) IN POPLAR INVESTIGATED WITH CHEMOMETRICS AND 2D-NMR

    Science.gov (United States)

    An understanding of the lignification process is of vital importance, especially for the pulp and paper industry. Cinnamoyl-coa reductase (CCR) is an enzyme that plays a central role in the lignification process. Previous results have shown that down-regulation of CCR decreases the lignin content. B...

  7. Blood expression levels of chemokine receptor CCR3 and chemokine CCL11 in age-related macular degeneration

    DEFF Research Database (Denmark)

    Falk, Mads Krüger; Singh, Amardeep; Faber, Carsten

    2014-01-01

    Dysregulation of the CCR3/CCL11 pathway has been implicated in the pathogenesis of choroidal neovascularisation, a common feature of late age-related macular degeneration (AMD). The aim of this study was to investigate the expression of CCR3 and its ligand CCL11 in peripheral blood in patients...

  8. MC148 encoded by human molluscum contagiosum poxvirus is an antagonist for human but not murine CCR8

    DEFF Research Database (Denmark)

    Lüttichau, H R; Gerstoft, J; Schwartz, T W

    2001-01-01

    The viral CC chemokines MC148, encoded by the poxvirus molluscum contagiosum, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in parallel with human CCR8. In calcium mobilization assays, vMIP-I acted...... as a high-affinity agonist, whereas vMIP-II acted as a low-affinity antagonist on the murine CCR8 as well as the human CCR8. MC148 was found to bind and block responses through the human CCR8 with high affinity, but surprisingly MC148 was unable to bind and block responses through the murine CCR8. Because...... MC148 is the only high-affinity antagonist known to target and be selective for CCR8, MC148 is a valuable tool to decipher the role played by CCR8 in the immune system. This study shows that MC148 could not be used in murine inflammatory models; however, it will be interesting to see whether it can...

  9. Evidence favoring the involvement of CC chemokine receptor (CCR) 5 in T-lymphocyte accumulation in optic neuritis

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Ransohoff, R M; Jensen, J

    2003-01-01

    To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON).......To define the relationships between levels of chemokine receptor (CCR)5+ T-cells in blood and cerebrospinal fluid (CSF) of optic neuritis (ON) and control patients (CON)....

  10. Exploring a model of human chemokine receptor CCR2 in presence of TAK779: A membrane based molecular dynamics study

    Science.gov (United States)

    Balupuri, Anand; Sobhia, M. Elizabeth

    2014-04-01

    Chemokine receptor 2 (CCR2) is a G-protein coupled receptor (GPCR) and a crucial target for various inflammation-driven diseases. In the present study, molecular docking and molecular dynamics simulations were performed on a CCR2 homology model. This work includes the comparative MD simulations of uncomplexed and ‘antagonist-complexed’ CCR2 models. These simulations yield insights into the binding mechanism of antagonist TAK779 and improve the understanding of various structural changes induced by the ligand in the CCR2 protein. Here, one 20 ns MD simulation was carried out on the uncomplexed CCR2 model in lipid bilayer to explore the effects of lipid membrane on the protein. Another 20 ns MD simulation was performed under the similar conditions on the docked CCR2-TAK779 complex. An alteration in the position and orientation of the ligand in binding site was observed after the simulation. Examination of protein-ligand complex suggested that TAK779 produced a greater structural change on the TM-III, TM-IV, TM-V and TM-VI than TM-I, TM-II and TM-VII. Interaction networks involving the conserved residues of uncomplexed and ‘antagonist-complexed’ CCR2 models were also examined. The major difference was observed to be the role of conserved residues of the DRY motif of TM-III and the NPxxY motif of TM-VII of CCR2.

  11. Preclinical development and qualification of ZFN-mediated CCR5 disruption in human hematopoietic stem/progenitor cells

    Directory of Open Access Journals (Sweden)

    David L DiGiusto

    2016-01-01

    Full Text Available Gene therapy for HIV-1 infection is a promising alternative to lifelong combination antiviral drug treatment. Chemokine receptor 5 (CCR5 is the coreceptor required for R5-tropic HIV-1 infection of human cells. Deletion of CCR5 renders cells resistant to R5-tropic HIV-1 infection, and the potential for cure has been shown through allogeneic stem cell transplantation with naturally occurring homozygous deletion of CCR5 in donor hematopoietic stem/progenitor cells (HSPC. The requirement for HLA-matched HSPC bearing homozygous CCR5 deletions prohibits widespread application of this approach. Thus, a strategy to disrupt CCR5 genomic sequences in HSPC using zinc finger nucleases was developed. Following discussions with regulatory agencies, we conducted IND-enabling preclinical in vitro and in vivo testing to demonstrate the feasibility and (preclinical safety of zinc finger nucleases-based CCR5 disruption in HSPC. We report here the clinical-scale manufacturing process necessary to deliver CCR5-specific zinc finger nucleases mRNA to HSPC using electroporation and the preclinical safety data. Our results demonstrate effective biallelic CCR5 disruption in up to 72.9% of modified colony forming units from adult mobilized HSPC with maintenance of hematopoietic potential in vitro and in vivo. Tumorigenicity studies demonstrated initial product safety; further safety and feasibility studies are ongoing in subjects infected with HIV-1 (NCT02500849@clinicaltrials.gov.

  12. Structural insight into a novel human CCR5-V130I variant associated with resistance to HIV-1 infection.

    Science.gov (United States)

    Stambouli, Nejla; Wei, Ning-Ning; Jlizi, Asma; Aissa, Samah; Abdelmalek, Rim; Kilani, Baderredine; Slim, Amine; Tiouiri, Ben Aissa Hanen; Dridi, Mahdi; Hamza, Adel; Ben Ammar Elgaied, Amel

    2014-01-01

    We report the identification of a novel CC chemokine receptor 5 (CCR5) variant that seems associated with resistance to HIV-1 infection. The V130I mutation of the CCR5 receptor is located in the intracellular loop ICL2 known as DRY box and described in the literature as a nonsynonymous mutation present in nonhuman primates group. Extensive molecular modeling and dynamics simulations were performed to elucidate the mechanism by which the V130I mutation may induce conformational change of the CCR5 folding protein and prevent the interaction with the β-arrestin protein. Our study provides new mechanistic insight into how a specific mutation in the regulatory domain of CCR5 might alter the structural folding of the DRY box and the possible ICL2 loop binding with the β-arrestin protein, as described in our previous computational study. The results from our large-scale simulations complement recent experimental results and clinical features and offer useful insights into the mechanism behind CCR5 protein folding and signal transduction. In order for HIV, the entry of the virus to the cells must fuse with the CCR5 receptor that sits on the surface of T-helper immune cells. The described V130I mutation in the gene encoding the CCR5 protein may results in a defective CCR5-Arrestin binding complex that blocks entry of the virus.

  13. CCR5 mediates HIV-1 Tat-induced neuroinflammation and influences morphine tolerance, dependence, and reward.

    Science.gov (United States)

    Gonek, Maciej; McLane, Virginia D; Stevens, David L; Lippold, Kumiko; Akbarali, Hamid I; Knapp, Pamela E; Dewey, William L; Hauser, Kurt F; Paris, Jason J

    2017-11-13

    The HIV-1 regulatory protein, trans-activator of transcription (Tat), interacts with opioids to potentiate neuroinflammation and neurodegeneration within the CNS. These effects may involve the C-C chemokine receptor type 5 (CCR5); however, the behavioral contribution of CCR5 on Tat/opioid interactions is not known. Using a transgenic murine model that expresses HIV-1 Tat protein in a GFAP-regulated, doxycycline-inducible manner, we assessed morphine tolerance, dependence, and reward. To assess the influence of CCR5 on these effects, mice were pretreated with oral vehicle or the CCR5 antagonist, maraviroc, prior to morphine administration. We found that HIV-1 Tat expression significantly attenuated the antinociceptive potency of acute morphine (2-64 mg/kg, i.p.) in non-tolerant mice. Consistent with this, Tat attenuated withdrawal symptoms among morphine-tolerant mice. Pretreatment with maraviroc blocked the effects of Tat, reinstating morphine potency in non-tolerant mice and restoring withdrawal symptomology in morphine-tolerant mice. Twenty-four hours following morphine administration, HIV-1 Tat significantly potentiated (∼3.5-fold) morphine-conditioned place preference and maraviroc further potentiated these effects (∼5.7-fold). Maraviroc exerted no measurable behavioral effects on its own. Protein array analyses revealed only minor changes to cytokine profiles when morphine was administered acutely or repeatedly; however, 24 h post morphine administration, the expression of several cytokines was greatly increased, including endogenous CCR5 chemokine ligands (CCL3, CCL4, and CCL5), as well as CCL2. Tat further elevated levels of several cytokines and maraviroc pretreatment attenuated these effects. These data demonstrate that CCR5 mediates key aspects of HIV-1 Tat-induced alterations in the antinociceptive potency and rewarding properties of opioids. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Differential evolution of a CXCR4-using HIV-1 strain in CCR5wt/wt and CCR5∆32/∆32 hosts revealed by longitudinal deep sequencing and phylogenetic reconstruction.

    Science.gov (United States)

    Le, Anh Q; Taylor, Jeremy; Dong, Winnie; McCloskey, Rosemary; Woods, Conan; Danroth, Ryan; Hayashi, Kanna; Milloy, M-J; Poon, Art F Y; Brumme, Zabrina L

    2015-12-03

    Rare individuals homozygous for a naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5∆32/∆32) are resistant to infection by CCR5-using ("R5") HIV-1 strains but remain susceptible to less common CXCR4-using ("X4") strains. The evolutionary dynamics of X4 infections however, remain incompletely understood. We identified two individuals, one CCR5wt/wt and one CCR5∆32/∆32, within the Vancouver Injection Drug Users Study who were infected with a genetically similar X4 HIV-1 strain. While early-stage plasma viral loads were comparable in the two individuals (~4.5-5 log10 HIV-1 RNA copies/ml), CD4 counts in the CCR5wt/wt individual reached a nadir of 250 cells/mm(3) in the CCR5∆32/∆32 individual. Ancestral phylogenetic reconstructions using longitudinal envelope-V3 deep sequences suggested that both individuals were infected by a single transmitted/founder (T/F) X4 virus that differed at only one V3 site (codon 24). While substantial within-host HIV-1 V3 diversification was observed in plasma and PBMC in both individuals, the CCR5wt/wt individual's HIV-1 population gradually reverted from 100% X4 to ~60% R5 over ~4 years whereas the CCR5∆32/∆32 individual's remained consistently X4. Our observations illuminate early dynamics of X4 HIV-1 infections and underscore the influence of CCR5 genotype on HIV-1 V3 evolution.

  15. Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

    DEFF Research Database (Denmark)

    Hjorto, Gertrud M.; Larsen, Olav; Steen, Anne

    2016-01-01

    The CCR7 ligands CCL19 and CCL21 are increasingly recognized as functionally different (biased). Using mature human dendritic cells (DCs), we show that CCL19 is more potent than CCL21 in inducing 3D chemotaxis. Intriguingly, CCL21 induces prolonged and more efficient ERK1/2 activation compared...... identify a molecular switch in the top of TM7 important for keeping CCR7 in an inactive conformation (Tyr312), as introduction of the chemokine receptor-conserved Glu (or Ala) induces high constitutive activity. Summarized, we show that the interaction of the tail of CCL21 with polysialic acid is needed...

  16. CCR1, an enzyme required for lignin biosynthesis in Arabidopsis, mediates cell proliferation exit for leaf development

    DEFF Research Database (Denmark)

    Xue, Jingshi; Luo, Dexian; Xu, Deyang

    2015-01-01

    development is as yet poorly understood. By genetic screening and characterization of Arabidopsis mutants defective in exit from cell proliferation, we show that the product of the CINNAMOYL CoA REDUCTASE (CCR1) gene, which is required for lignin biosynthesis, participates in the process of cell proliferation...... exit in leaves. CCR1 is expressed basipetally in the leaf, and ccr1 mutants exhibited multiple abnormalities, including increased cell proliferation. The ccr1 phenotypes are not due to the reduced lignin content, but instead are due to the dramatically increased level of ferulic acid (Fe......A), an intermediate in lignin biosynthesis. FeA is known to have antioxidant activity, and the levels of reactive oxygen species (ROS) in ccr1 were markedly reduced. We also characterized another double mutant in CAFFEIC ACID O-METHYLTRANSFERASE (comt) and CAFFEOYL CoA 3-O-METHYLTRANSFERASE (ccoaomt), in which the Fe...

  17. The impact of CCR5-Δ32 deletion on C-reactive protein levels and cardiovascular disease

    DEFF Research Database (Denmark)

    Dinh, Khoa M; Pedersen, Ole B; Petersen, Mikkel S

    2015-01-01

    BACKGROUND AND PURPOSE: The C-C chemokine receptor 5-Δ32 deletion (CCR5-Δ32) has been associated with lower levels of C-reactive protein (CRP), but the effect on cardiovascular diseases is uncertain. This study addresses the impact of CCR5-Δ32 on the risk of low-grade inflammation...... and hospitalization with cardiovascular diseases in a large cohort of blood donors. METHODS: Genotyping of 15,206 healthy participants from The Danish Blood Donor Study for CCR5-Δ32 was performed and combined with CRP measurements and questionnaire data. Cardiovascular disease diagnoses were identified by ICD-10...... codes in the Danish National Patient Registry. RESULTS: CCR5-Δ32-carriers had a higher risk of hospitalization for cardiovascular diseases when compared with wild-type homozygotes (hazard ratio = 1.35, 95%-confidence interval: 1.00-1.87). CRP levels were unaffected by the CCR5-Δ32 deletion. CONCLUSION...

  18. The Role of News Teasers in Processing TV News and Commercials.

    Science.gov (United States)

    Cameron, Glen T.; And Others

    1991-01-01

    Explores the role of news teasers on memory and attention for commercials in evening newscasts. Finds that they enhance moderately the primacy-recency pattern found in visual and verbal memory scores. Finds that news teasers appear to have an effect on processing strategies employed by viewers. (SR)

  19. News Sources, Gender and Majority-Minority in Danish TV News Programs

    DEFF Research Database (Denmark)

    Fiig, Christina

    In this paper, I am going to identify some central methodological challenges in relation to a project on TV-news and news sources in a perspective of intersectionality and to sketch a research design. In what follows, I will present some methodological issues and research designs of previous...

  20. When good news is bad news: explicating the moderated mediation dynamic behind the reversed mobilization effect

    NARCIS (Netherlands)

    Schuck, A.R.T.; de Vreese, C.H.

    2012-01-01

    This study investigates the mobilizing potential of positive news framing on opponents of a referendum proposal. On the basis of an experiment (N = 470), using bootstrapping as a method to assess conditional indirect effects, mediation analysis showed that positive news framing—endorsing a