Swart, Joëlle; Peters, Chris; Broersma, Marcel
academic discussions surrounding these shifts are often explored in terms of normative ideals ascribed to political systems or civic cultures, we propose to reposition the debate by departing from the practices and preferences of the news user instead. Therefore, we deconstruct and translate the concept...... 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...
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
EPS AWARD WINNERS Award for outreach to Physics Education authors; TEACHER TRAINING Helping teachers specialize in physics; AAPT SUMMER MEETING The science of light; AAPT SUMMER MEETING Do you believe in skepticism?; E-LEARNING Massive investment in Swedish online learning; UK SCIENCE YEAR News from Science Year; 11-16 CURRICULUM Naming the energy parts; TEACHER TRAINING Electronic Discussion Group for Trainee Teachers; PUBLICATIONS Physics on Course 2002; WALES Physics in Powys; HIGHER EDUCATION HE solutions to the physics teacher shortage; SCOTLAND The 27th Scottish Stirling Meeting; NORTHERN IRELAND Belfast physics teachers' meeting; SCOTLAND Physics Summer School, Edinburgh 2001; AAPT SUMMER MEETING Physics education research: massive growth; AAPT SUMMER MEETING Just-In-Time Teaching;
Full Text Available UIA NewsA Thinking Head and a Nursing CowThe Regular General Meeting of the Members of the Self-Regulatory Organization IndependentPartnership “The Baikal Association of Architects and Engineers” of March 23“BukhArt”: the Beginning of the Second Five-Year PeriodThe VIIth Forum of Architects-Skiers from Siberia and UralThe Second Landscape Conference in Krasnoyarsk“Geo-Decor”, so Simple and Unexpected254 Years and the 20th AnniversaryThe Book “Irkutsk Architects” Arkhangelsk Museum of Wooden Architecture «Malye Korely»The Valletta Principles for the Safeguarding and Management of Historic Cities, Towns and Urban AreasCreative Project in VologdaThe Nomad 2. Circles and Spirals
The development of theories and techniques for big data analytics offers tremendous flexibility for investigating large-scale events and patterns that emerge over space and time. In this research, we utilize a unique open-access dataset "The Global Data on Events, Location and Tone" (GDELT) to model the image of China in mass media, specifically, how China has related to the rest of the world and how this connection has evolved upon time based on an autoregressive integrated moving average (ARIMA) model. The results of this research contribute both in methodological and empirical perspectives: We examined the effectiveness of time series models in predicting trends in long-term mass media data. In addition, we identified various types of connection strength patterns between China and its top 15 related countries. This study generates valuable input to interpret China's diplomatic and regional relations based on mass media data, as well as providing methodological references for investigating international rel...
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...
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...
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…
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...
Full Text Available BACKGROUND: Ccr4-Not is a highly conserved multi-protein complex consisting in yeast of 9 subunits, including Not5 and the major yeast deadenylase Ccr4. It has been connected functionally in the nucleus to transcription by RNA polymerase II and in the cytoplasm to mRNA degradation. However, there has been no evidence so far that this complex is important for RNA degradation in the nucleus. METHODOLOGY/PRINCIPAL FINDINGS: In this work we point to a new role for the Ccr4-Not complex in nuclear RNA metabolism. We determine the importance of the Ccr4-Not complex for the levels of non-coding nuclear RNAs, such as mis-processed and polyadenylated snoRNAs, whose turnover depends upon the nuclear exosome and TRAMP. Consistently, mutation of both the Ccr4-Not complex and the nuclear exosome results in synthetic slow growth phenotypes. We demonstrate physical interactions between the Ccr4-Not complex and the exosome. First, Not5 co-purifies with the exosome. Second, several exosome subunits co-purify with the Ccr4-Not complex. Third, the Ccr4-Not complex is important for the integrity of large exosome-containing complexes. Finally, we reveal a connection between the Ccr4-Not complex and TRAMP through the association of the Mtr4 helicase with the Ccr4-Not complex and the importance of specific subunits of Ccr4-Not for the association of Mtr4 with the nuclear exosome subunit Rrp6. CONCLUSIONS/SIGNIFICANCE: We propose a model in which the Ccr4-Not complex may provide a platform contributing to dynamic interactions between the nuclear exosome and its co-factor TRAMP. Our findings connect for the first time the different players involved in nuclear and cytoplasmic RNA degradation.
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: firstname.lastname@example.org). 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
, 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; email@example.com. 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
Full Text Available Age-related macular degeneration (AMD is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet" AMD, characterized by the development of choroidal neovacularization (CNV, could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin targeting for CNV.
reference to data availability and the decisions that might be made advertising promotions and product properties. Other uses and possible further...system for marketing new products. NEWS is designed to distinguish the variables and relations that are usually of interest for market -planning by
International Journal of Rehabilitation Research, 1987
Rehabilitation news items include, among others: a midpoint review of the implementation of the World Programme of Action Concerning Disabled Persons, an international study on the impact of new technologies on employment of disabled people, and a U.S. project to investigate disability service provision and innovations in other countries. (JDD)
D.J.C. van Dijk (Dick)
textabstractNews plays a crucial role in determining prices in financial markets. In an efficient market, current prices fully and correctly reflect all available information, such that only truly new information leads to price adjustment. This lecture shows that using high-frequency data makes it p
Soler, Dulce; Humphreys, Tricia L; Spinola, Stanley M; Campbell, James J
The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin-dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human TH populations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell-attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of TH subsets. We find CCR10 expressed by only a minority (approximately 30%) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However, essentially all members of the relatively small "effector" (CLA+/CCR4+/CD27-/CCR7-) skin-homing TH population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10% express CCR10. This suggests for the 2 models of TH skin homing studied here that CCR10+ TH cells have no advantage over other CLA+/CCR4+ TH cells in homing to cutaneous sites. We conclude that the skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized "effector" cutaneous TH cells to and/or within epidermal microenvironments.
Television news range among the most extensively investigated topics in communication studies. The book contributes to television news research by focusing on whether and how news viewers who watch the same news program form similar or different interpretations. The author develops a novel concept o
Maksl, Adam; Ashley, Seth; Craft, Stephanie
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…
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...
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...
A list of 296 ecologists of various description but more or less connected with Malesia occurs in Wallaceana no. 3 (Oct. 1974), a supplement of 183 in no. 4 (April 1975). Editor Dr. J.I. Furtado, School of Biological Sciences, University of Malaya, Pantai Valley, Kuala Lumpur. Please notify the Edit
Stormwater management modelers now have a new publication:Storm Water Management Modelling News and Notes. SWMM News and Notes features articles concerning new developments and research in the stormwater field, as well as new product reviews, dissertations, and books.
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...
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....
transform the way Americans receive news and information. But Saul Hansell of the New York Times believes none of this is a surprise to the media elites...References Anderson, B. (2004). “News Flash: Journalism, Infotainment and the Bottom-Line Business of Broadcast News.” Jossey- Bass , pp
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
胡珀; 黄民烈; 朱小燕
Today’s news readers can be easily overwhelmed by the numerous news articles online. To cope with information overload, online news media publishes timelines for continuously developing news topics. However, the timeline summary does not show the relationship of storylines, and is not intuitive for readers to comprehend the development of a complex news topic. In this paper, we study a novel problem of exploring the interactions of storylines in a news topic. An interaction of two storylines is signified by informative news events that play a key role in both storylines. Storyline interactions can indicate key phases of a news topic, and reveal the latent connections among various aspects of the story. We address the coherence between news articles which is not considered in traditional similarity-based methods, and discover salient storyline interactions to form a clear, global picture of the news topic. User preference can be naturally integrated into our method to generate query-specific results. Comprehensive experiments on ten news topics show the effectiveness of our method over alternative approaches.
Schmidt, Ana Lucía; Del Vicario, Michela; Quattrociocchi, Walter
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. PMID:28265082
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
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...
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 ...
Papa, A; Papadimitriou, E; Adwan, G; Clewley, J P; Malissiovas, N; Ntoutsos, I; Alexiou, S; Antoniadis, A
The frequency of CCR5 and CCR2 alleles in human immunodeficiency virus (HIV)-positive and HIV-negative populations of Northern Greece was investigated. The frequency of the CCR5Delta32 allele among the HIV-negative subjects was 0.052, while it was approximately two-fold lower among the seropositives, suggesting that the heterozygous genotype confers a partial resistance to the HIV infection. No significant difference in CCR2 allele frequency between the two groups was observed.
Samira H. Al-Mahruqi
Full Text Available Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5!32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%, HHE (20%, HHA (14% and HHF*2 (12%.
Al-Mahruqi, Samira H; Zadjali, Fahad; Beja-Pereira, Albano; Koh, Crystal Y; Balkhair, Abdullah; Al-Jabri, Ali A
Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5Δ32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2 (12%).
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 firstname.lastname@example.org; 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
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...... for the story and to do live stand ups –on location. Teams feed footage (pictures, sound and interviews) with low-cost satelliteequipment to DR. Here, other reporters edit the material to stories for allplatforms. The workflow is split into several parts. This is a fundamental change with many implications...... 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...
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.
Zare-Bidaki, Mohammad; Karimi-Googheri, Masoud; Hassanshahi, Gholamhossein; Zainodini, Nahid; Arababadi, Mohammad Kazemi
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 (Δ 32) in the exon 1 of the CCR5 gene, which is known as CCR5 Δ 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 Δ 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 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.
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
Mehlotra, Rajeev K; Hall, Noemi B; Bruse, Shannon E; John, Bangan; Blood Zikursh, Melinda J; Stein, Catherine M; Siba, Peter M; Zimmerman, Peter A
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-valuesCCR5 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.
Although there are many news search engines on the Web, finding the news items one wants can be challenging. Choosing appropriate search terms is one of the biggest challenges. Unless one has seen the article that one is seeking, it is often difficult to select words that were used in the headline or text of the article. The limited archives of…
<正>A distinguished scientist was participating in a panel discussion on the results of the nation’s future water supply．“Gentlemen,” he said．“I have some good news and bad news for you,Our study shows that by the year 2010 everyone will be drinking recycled sewage from
Hansen, Lars Kai; Arvidsson, Adam; Nielsen, Finn Årup
. In this paper we explore the apparent paradox in a quantitative analysis of information diffusion on Twitter. Twitter is interesting in this context as it has been shown to present both the characteristics social and news media. The basic measure of virality in Twitter is the probability of retweet. Twitter...... is different from email in that retweeting does not depend on pre-existing social relations, but often occur among strangers, thus in this respect Twitter may be more similar to traditional news media. We therefore hypothesize that negative news content is more likely to be retweeted, while for non-news tweets...... 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...
Sellebjerg, F; Kristiansen, Thomas Birk; Wittenhagen, P
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...
Holse, Mille; Assing, Kristian; Poulsen, Lars K.
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....
Marco Toledo Bastos
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.
T.A. Knoch (Tobias); J. Langowski (Jörg)
textabstractDespite the successful linear sequencing of the human genome its three-dimensional structure is widely unknown, although it is important for gene regulation and replication. For a long time the interphase nucleus has been viewed as a 'spaghetti soup' of DNA without much internal struc
Graber, Doris A.
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)
Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...
Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Oc...
Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.
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.
Hartley, Jannie Møller
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...... 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?...
Ren, Hui; Yu, Daoyong; Ge, Baosheng; Cook, Brian; Xu, Zhinan; Zhang, Shuguang
Chemokine receptors belong to a class of integral membrane G-protein coupled receptors (GPCRs) and are responsible for transmitting signals from the extracellular environment. However, the structural changes in the receptor, connecting ligand binding to G-protein activation, remain elusive for most GPCRs due to the difficulty to produce them for structural and functional studies. We here report high-level production in E.coli of 4 human GPCRs, namely chemokine receptors (hCRs) CCR5, CCR3, CXCR4 and CX3CR1 that are directly involved in HIV-1 infection, asthma and cancer metastasis. The synthetic genes of CCR5, CCR3, CXCR4 and CX3CR1 were synthesized using a two-step assembly/amplification PCR method and inserted into two different kinds of expression systems. After systematic screening of growth conditions and host strains, TB medium was selected for expression of pEXP-hCRs. The low copy number pBAD-DEST49 plasmid, with a moderately strong promoter tightly regulated by L-arabinose, proved helpful for reducing toxicity of expressed membrane proteins. The synthetic Trx-hCR fusion genes in the pBAD-DEST49 vector were expressed at high levels in the Top10 strain. After a systematic screen of 96 detergents, the zwitterionic detergents of the Fos-choline series (FC9-FC16) emerged as the most effective for isolation of the hCRs. The FC14 was selected both for solubilization from bacterial lysates and for stabilization of the Trx-hCRs during purification. Thus, the FC-14 solubilized Trx-hCRs could be purified using size exclusion chromatography as monomers and dimers with the correct apparent MW and their alpha-helical content determined by circular dichroism. The identity of two of the expressed hCRs (CCR3 and CCR5) was confirmed using immunoblots using specific monoclonal antibodies. After optimization of expression systems and detergent-mediated purification procedures, we achieved large-scale, high-level production of 4 human GPCR chemokine receptor in a two
Full Text Available Chemokine receptors belong to a class of integral membrane G-protein coupled receptors (GPCRs and are responsible for transmitting signals from the extracellular environment. However, the structural changes in the receptor, connecting ligand binding to G-protein activation, remain elusive for most GPCRs due to the difficulty to produce them for structural and functional studies. We here report high-level production in E.coli of 4 human GPCRs, namely chemokine receptors (hCRs CCR5, CCR3, CXCR4 and CX3CR1 that are directly involved in HIV-1 infection, asthma and cancer metastasis. The synthetic genes of CCR5, CCR3, CXCR4 and CX3CR1 were synthesized using a two-step assembly/amplification PCR method and inserted into two different kinds of expression systems. After systematic screening of growth conditions and host strains, TB medium was selected for expression of pEXP-hCRs. The low copy number pBAD-DEST49 plasmid, with a moderately strong promoter tightly regulated by L-arabinose, proved helpful for reducing toxicity of expressed membrane proteins. The synthetic Trx-hCR fusion genes in the pBAD-DEST49 vector were expressed at high levels in the Top10 strain. After a systematic screen of 96 detergents, the zwitterionic detergents of the Fos-choline series (FC9-FC16 emerged as the most effective for isolation of the hCRs. The FC14 was selected both for solubilization from bacterial lysates and for stabilization of the Trx-hCRs during purification. Thus, the FC-14 solubilized Trx-hCRs could be purified using size exclusion chromatography as monomers and dimers with the correct apparent MW and their alpha-helical content determined by circular dichroism. The identity of two of the expressed hCRs (CCR3 and CCR5 was confirmed using immunoblots using specific monoclonal antibodies. After optimization of expression systems and detergent-mediated purification procedures, we achieved large-scale, high-level production of 4 human GPCR chemokine receptor in a
Masip, Pere; Guallar, Javier; Suau, Jaume; Ruiz-Caballero, Carlos; Peralta, Miquel
Based on a quantitative approach, this paper presents some of the preliminary results of a research project focused on the analysis of the motivations that encourage citizens to actively participate in online news media, using the mechanisms provided by their websites, and through open social network platforms. The findings show that, although there is a widespread discourse of distrust in connection to journalists and the traditional media institutions, as well as general criticism of the ac...
case study, ways to work with the influence of endogenous factors (keywords, language settings, geo-location, Web history and clicking behaviour) and mitigate the effects of the exogenous factors (experimentation and randomisation) are suggested. Then, a new approach to studying search results is put......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...... forward, which builds on purposeful sampling of real-world participants or constructed research profiles. Finally, perspectives for news and journalism scholars in studying algorithmically generated content in a broader context are offered....
A. Paz Alencar (Amanda); Deuze, M.
textabstractThis 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
Liu, Fa-Yu; Safdar, Jawad; Li, Zhen-Ning; Fang, Qi-Gen; Zhang, Xu; Xu, Zhong-Fei; Sun, Chang-Fu
Migration and invasion of tumor cells are essential prerequisites for the formation of metastasis in malignant diseases. Previously, we have reported that CC chemokine receptor 7 (CCR7) regulates the mobility of squamous cell carcinoma of head and neck (SCCHN) cells through several pathways, such as integrin and cdc42. In this study, we investigated the connection between CCR7 and mitogen-activated protein kinase (MAPK) family members, and their influence on cell invasion and migration in metastatic SCCHN cells. Western blotting, immunostaining and fluorescence microcopy were used to detect the protein expression and distribution of MAPKs, and the Migration assay, Matrigel invasion assay and wound-healing assay to detect the role of MAPKs in CCR7 regulating cell mobility. To analyze the correlation between CCR7 and MAPK activity and clinicopathological factors immunohistochemical staining was emplyed. The results showed stimulation of CCL19 and the activation of CCR7 could induce ERK1/2 and JNK phosphorylation, while it had no efect on p38. After activation, ERK1/2 and JNK promoted E-cadherin low expression and Vimentin high expression. The MAPK pathway not only mediated CCR7 induced cell migration, but also mediated invasion speed. The immunohistochemistry results showed that CCR7 was correlated with the phosphorylation of ERK1/2 and JNK in SCCHN, and these molecules were all associated with lymph node metastasis. Therefore, our study demonstrates that MAPK members (ERK1/2 and JNK) play a key role in CCR7 regulating SCCHN metastasis.
Full Text Available 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 page such as Google news. The information is stored in XML format. A scientific news aggregator helps in structuring online resources into useful contents. These contents are automatically fetched from several online resources available on the Internet and categorized on a separate page. Mostly, RSS feeds are used to done this job. Atom feeds are more detailed and having advance feature than RSS feeds, helps to improve the performance of scientific news aggregator by giving more updated information. A modern view of an aggregator offers a friendly user interface for users by merging the news content. We are working on an interesting approach for the design and implementation of news aggregators which will collect and aggregate data from the web to acquire unstructured information and transform it into data that could be understood and dynamically processed. The proposed approach will combine various mechanisms in order to connect to the data sources specified, identify the categories of articles, extract the corresponding pieces of news and automatically place them into the knowledge database and automatically extract the new pieces of information in the knowledge base and display them on the Science News section
Legg, Angela M; Sweeny, Kate
Information often comes as a mix of good and bad news, prompting the question, "Do you want the good news or the bad news first?" In such cases, news-givers and news-recipients differ in their concerns and considerations, thus creating an obstacle to ideal communication. In three studies, we examined order preferences of news-givers and news-recipients and the consequences of these preferences. Study 1 confirmed that news-givers and news-recipients differ in their news order preferences. Study 2 tested two solutions to close the preference gap between news-givers and recipients and found that both perspective-taking and priming emotion-protection goals shift news-givers' delivery patterns to the preferred order of news-recipients. Study 3 provided evidence that news order has consequences for recipients, such that opening with bad news (as recipients prefer) reduces worry, but this emotional benefit undermines motivation to change behavior.
News about scientific advances in cancer prevention, program activities, and new projects are included here in NCI press releases and fact sheets, articles from the NCI Cancer Bulletin, and Clinical Trial News from the NCI website.
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...
Wu, Yingping; Deng, Riqiang; Wu, Wenyan
The G protein-coupled receptor of human chemokine receptor 5 (CCR5) is a key target in the human immunodeficiency virus (HIV) infection process due to its major involvement in binding to the HIV type 1 (HIV-1) envelope glycoprotein gp120 and facilitating virus entry into the cells. The identification of naturally occurring CCR5 mutations (especially CCR5 delta-32) has allowed us to address the CCR5 molecule as a promising target to prevent or resist HIV infection in vivo. To obtain high-affinity peptides that can be used to block CCR5, CCR5 analogs with high conformational similarity are required. In this study, two recombinant proteins named CCR5 N-Linker-E2 and CCR5 mN-E1-E2 containing the fragments of the CCR5 N-terminal, the first extracellular loop or the second extracellular loop are cloned from a full-length human CCR5 cDNA. The recombinant human CCR5 analogs with self-cleavage activity of the intein Mxe or Ssp in the vector pTwinI were then produced with a high-yield expression and purification system in Escherichia coli. Experiments of extracellular epitope-activity identification (such as immunoprecipitation and indirective/competitive enzyme-linked immunosorbent assay) confirmed the close similarity between the epitope activity of the CCR5 analogs and that of the natural CCR5, suggesting the applicability of the recombinant CCR5 analogs as antagonists of the chemokine ligands. Subsequent screening of high-affinity peptides from the phage random-peptides library acquired nine polypeptides, which could be used as CCR5 peptide antagonists. The CCR5 analogs and affinity peptides elucidated in this paper provide us with a basis for further study of the mechanism of inhibition of HIV-1 infection.
This article deals with mass media in modern democratic societies, using the example of Israeli news reports in German television (TV) news. Central to this interest are processes of mediating politics: political socialisation and education; that is to say, empowering citizens via TV news to participate in democratic processes. The article…
McFarlane, Delano J; Elhadad, Noémie; Kukafka, Rita
An important task performed during the analysis of health news coverage is the identification of news articles that are related to a specific health topic (e.g. obesity). This is often done using a combination of keyword searching and manual encoding of news content. Statistical language models and their evaluation metric, perplexity, may help to automate this task. A perplexity study of obesity news was performed to evaluate perplexity as a measure of the similarity of news corpora to obesity news content. The results of this study showed that perplexity increased as news coverage became more general relative to obesity news (obesity news approximately 187, general health news approximately 278, general news approximately 378, general news across multiple publishers approximately 382). This indicates that language model perplexity can measure the similarity news content to obesity news coverage, and could be used as the basis for an automated health news classifier.
Legg, Angela M; Sweeny, Kate
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.
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.
Trigt, Anna Maria van
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 profe
Giles, Ray, Ed.
This fall 2002 newsletter from the Community College League of California contains several articles, news stories, and the brochure from the 2002 Annual Convention, "Celebrating the Way California LEARNS." Articles include: (1) "Nursing Shortage Poses Dilemma for Colleges: Access vs. Efficiency," a discussion of the debate over…
St. Lifer, Evan; Olson, Renee; Milliot, Jim; Bing, Jonathan
Reviews library news for 1997. Highlights public library budgets, examined by number of patrons served; Internet filters and censorship; librarians and the media; private and government funding sources; outsourcing; expectations for growth in the publishing industry, emphasizing the Asian economic crisis; and new ideas from the next generation of…
Journal of Blacks in Higher Education, 1998
The "News and Views" section of this journal contains reports and comments on various issues related to current aspects of black higher education. The topics reviewed include affirmative action, college admissions policies, faculty diversity, and black enrollment in professional schools. Profiles of some black educators are also…
For all the progress in establishing a government news release system in China, the State Council Information Office acknowledges there is still much room for improvement Being a government spokesperson anywhere in the world is no easy job. It is particularly the case in China, where there is legislation in place on government information release. Cai Wu, Minister of the State Council Information Office,
Westley, Bruce H.
A revision of the first edition of "News Editing," this is a textbook for the newspaper editor. The duties of the editor are detailed, as are those of other newspaper employees. Among the basic editing skills the author includes suggestions for sentence structure, word usage, and vocabulary. Examples are given of editing for objectivity, handling…
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...
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...
The 25th anniversary of the Galapagos National Park. Fire at the Darwin Research Station. The control of introduced mammals. Good news about the Hood tortoises. The endangered land iguanas. Penguins, cormorants and flamingos in 1984. A workshop on national parks. International conservation award to Secretary Ripley. Visits and events at the Charles Darwin Research Station.
Jørndrup, Hanne; Bentsen, Martine
As newsroom staff around the world went about their day on 25 March 2015, hundreds of volunteers located in over 100 countries gathered to monitor their news media as part of the Fifth Global Media Monitoring Project (GMMP). The Global Media Monitoring Project (GMMP) is the world’s longest-running...
Schrøder, Kim Christian
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...... 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...
Kjetil Vaage Øie
Full Text Available This article focuses on user experiences on reading location-aware news on the mobile platform and aims to explore what experiences this kind of locative journalism generates and how such experiences change the users’ social interaction with news. We produced a specially designed mobile application and tailored news stories specific to this project called LocaNews in order to explore participants’ relation to the content in this journalistic format. The result is generated through a field study and a questionnaire of 32 people to find out how they experience the news presented in this format. The user participants’ responses are analyzed based on their news experiences, contextualizing places and their social interaction with the news within this form of journalism. Results showed that the local, semi-local and non-local user approaches the locative news in a different manner, but that the average user found this kind of news more interesting and more informative than ordinary news. The participants also have a problem identifying this as journalism, rather than an information service.
Toyoda, Hiromi; Miyagawa, Taku; Koike, Asako; Kanbayashi, Takashi; Imanishi, Aya; Sagawa, Yohei; Kotorii, Nozomu; Kotorii, Tatayu; Hashizume, Yuji; Ogi, Kimihiro; Hiejima, Hiroshi; Kamei, Yuichi; Hida, Akiko; Miyamoto, Masayuki; Imai, Makoto; Fujimura, Yota; Tamura, Yoshiyuki; Ikegami, Azusa; Wada, Yamato; Moriya, Shunpei; Furuya, Hirokazu; Takeuchi, Masaki; Kirino, Yohei; Meguro, Akira; Remmers, Elaine F; Kawamura, Yoshiya; Otowa, Takeshi; Miyashita, Akinori; Kashiwase, Koichi; Khor, Seik-Soon; Yamasaki, Maria; Kuwano, Ryozo; Sasaki, Tsukasa; Ishigooka, Jun; Kuroda, Kenji; Kume, Kazuhiko; Chiba, Shigeru; Yamada, Naoto; Okawa, Masako; Hirata, Koichi; Mizuki, Nobuhisa; Uchimura, Naohisa; Shimizu, Tetsuo; Inoue, Yuichi; Honda, Yutaka; Mishima, Kazuo; Honda, Makoto; Tokunaga, Katsushi
Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function.
... 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...
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 designing...... the Networking News workshop, offers an opportunity to make first hand studies of children’s IT supported social activities in an informal classroom setting....
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.
Nowadays Chinese people are attaching great importance to English news that not only offers worldwide information but gives a hand to English learners with their improvement in English. As is called the eyes of English news, headlines are partic-ularly important. Generally speaking, English news headlines are precise, brief and as attractive as possible. They have their own grammar features and vocabulary features while different devices are employed to make them expressive and striking.
Knudsen, T B; Kristiansen, T B; Katzenstein, T L;
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...
WANG Fei; HE Bei
Background Chronic obstructive pulmonary disease (COPD) is a progressive disease associated with a cellular inflammatory response mostly concerned with cigarette smoking.Chemokine receptors CCR1/5 play an important role in the inflammatory cells recruitment in the lung of COPD patients.The aim of this study was to determine the impact of cigarette smoking on the expression of CCR1/5 on inflammatory cells in induced sputum,and the relationship between the receptors expression and COPD severity.Methods Differential cells in induced sputum were counted and the optical densities of CCR1 and CCR5 on inflammatory cells in induced sputum from COPD patients (n=29),healthy smokers (n=11),and nonsmokers (n=6) were measured using immunocytochemistry.Concentrations of CCL3,the ligand of CCR1/5,in supernatant of induced sputum were detected by enzyme-linked immunosorbent assay.Results The expressions of CCR1 and CCR5 on inflammatory cells in healthy smokers were significantly higher than those in nonsmokers,and the expression of CCR1 in patients with COPD was significantly increased when compared with nonsmokers but not healthy smokers.The expressions of CCR1 and CCR5 on inflammatory cells in severe and very severe COPD patients were higher compared with mild and moderate COPD patients.CCL3 level was positively correlated with the total cell counts in induced sputum and smoking history,and negatively correlated with percentage of predicted FEV1.Conclusions Cigarette smoking could increase the expression of CCR1 on the inflammatory cells.Both CCR1 and CCR5 expressions on the inflammatory cells in induced sputum could be associated with COPD severity.
Hall, Spencer E; Mao, Allen; Nicolaidou, Vicky; Finelli, Mattea; Wise, Emma L; Nedjai, Belinda; Kanjanapangka, Julie; Harirchian, Paymann; Chen, Deborah; Selchau, Victor; Ribeiro, Sofia; Schyler, Sabine; Pease, James E; Horuk, Richard; Vaidehi, Nagarajan
Design of dual antagonists for the chemokine receptors CCR2 and CCR5 will be greatly facilitated by knowledge of the structural differences of their binding sites. Thus, we computationally predicted the binding site of the dual CCR2/CCR5 antagonist N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzohepten-8-yl] carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium (TAK-779), and a CCR2-specific antagonist N-(carbamoylmethyl)-3-trifluoromethyl benzamido-parachlorobenzyl 3-aminopyrrolidine (Teijin compound 1) in an ensemble of predicted structures of human CCR2 and CCR5. Based on our predictions of the protein-ligand interactions, we examined the activity of the antagonists for cells expressing thirteen mutants of CCR2 and five mutants of CCR5. The results show that residues Trp98(2.60) and Thr292(7.40) contribute significantly to the efficacy of both TAK-779 and Teijin compound 1, whereas His121(3.33) and Ile263(6.55) contribute significantly only to the antagonistic effect of Teijin compound 1 at CCR2. Mutation of residues Trp86(2.60) and Tyr108(3.32) adversely affected the efficacy of TAK-779 in antagonizing CCR5-mediated chemotaxis. Y49A(1.39) and E291A(7.39) mutants of CCR2 showed a complete loss of CCL2 binding and chemotaxis, despite robust cell surface expression, suggesting that these residues are critical in maintaining the correct receptor architecture. Modeling studies support the hypothesis that the residues Tyr49(1.39), Trp98(2.60), Tyr120(3.32), and Glu291(7.39) of CCR2 form a tight network of aromatic cluster and polar contacts between transmembrane helices 1, 2, 3, and 7.
This paper examines the paratextual structure of news texts, i.e., the headline system (superheadline, main headline, and subheadline) and the lead. In the first part of the paper T. A. van Dijk's interdisciplinary theory (1988) of "news in the press" is reviewed with special reference to the status and function assigned to the paratext.…
马海龙; 郑明华; 陈永平
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.
Reinecke Hansen, Kenneth
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...
Revkin, A. C.
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.
The chemokine receptor CCR5 regulates trafficking of immune cells of the lymphoid and the myeloid lineage (such as monocytes, macrophages and immature dendritic cells) and microglia. Because of this, there is an increasing recognition of the important role of CCR5 in the pathology of (neuro-) inflammatory diseases such as atherosclerosis and multiple sclerosis. Expression of CCR5 is under the control of a complexly organized promoter region upstream of the gene. The transcription factor cAMP-...
Lagane, Bernard; Garcia-Perez, Javier; Kellenberger, Esther
Maraviroc is a non-peptidic, low molecular weight CC chemokine receptor 5 (CCR5) ligand that has recently been marketed for the treatment of HIV infected individuals. This review discusses recent molecular modeling studies of CCR5 by homology to CXC chemokine receptor 4, their contribution to the understanding of the allosteric mode of action of the inhibitor and their potential for the development of future drugs with improved efficiency and preservation of CCR5 biological functions.
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
Wu, Kongtian; Xue, Xiaochang; Li, Meng; Qin, Xin; Zhang, Cun; Li, Weina; Hao, Qiang; Wang, Zenglu; Liu, Qian; Zhang, Wei; Zhang, Yingqi
Cysteine-cysteine chemokine receptor type 5 (CCR5) is an important co-receptor for human immunodeficiency virus (HIV) infection and CCR5 neutralizing agents have proven efficient in patients suffering from HIV infection. Here, we expressed and purified various CCR5 vaccines named rCCR5, PADRE-rCCR5, GST-C1 and GST-C2 composed of different epitopes of CCR5. Results showed that vaccines containing multiple epitopes (rCCR5 and PADRE-rCCR5) induced stronger immune responses than single-epitope ones (GST-C1 and GST-C2). In addition, the elicited antibodies can specifically bind CCR5(+) U937 but not CCR5(-) Wish cells. These results demonstrate that the CCR5 vaccines are useful for further research, especially for the in vitro preclinical evaluation of their potential as biological CCR5 neutralizing agents.
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
News language is formal,especially the high register vocabulary it employed to deliver the message unveiled by culturally and politically stamped style which challenges the translator a lot.Nida's formal and dynamic equivalence theory,Bielsa and Bassnett news translation theories and other methods and strategies are introduced to cope with these challenges and get the message across without distortion.
Calzada, J E; Nieto, A; Beraún, Y; Martín, J
In this study we investigated the possible role of two CCR5 gene polymorphisms, CCR5Delta32 deletion and CCR5 59029 A-->G promoter point mutation, in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease. These CCR5 polymorphisms were assessed in 85 seropositive (asymptomatic, n=53; cardiomyopathic, n=32) and 87 seronegative individuals. The extremely low frequency (0.009) of the CCR5Delta32 allele in our population did not allow us to analyse its possible influence on T. cruzi infection. We found no differences in the distribution of CCR5 59029 promoter genotype or phenotype frequencies between total chagasic patients and controls. However, we observed that the CCR5 59029-A/G genotype was significantly increased in asymptomatic with respect to cardiomyopathic patients (P=0.02; OR=0.33, 95% CI 0.10-0.94). In addition, the presence of the CCR5 59029-G allele was also increased in asymptomatics when compared with cardiomyopathics (P=0.02; OR=0.35, 95% CI 0.12-0.96). Our data suggest that the CCR5 59029 promoter polymorphism may be involved in a differential susceptibility to chagasic cardiomyopathy.
Rummel, Pia Cwarzko; Thiele, Stefanie; Hansen, Laerke Smidt
In addition to the 7TM receptor-conserved disulfide bridge between transmembrane helix (TM) 3 and extracellular loop (ECL) 2, chemokine receptors contain a disulfide bridge between the N-terminus and what previously was believed to be ECL-3. Recent crystal- and NMR-structures of CXCR4 and CXCR1...... 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...
Eskjær, Mikkel Fugl
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...
Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4+ lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4+ populations in blood, as well as by tis...
Trilling, D.; Schoenbach, K.
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 large-
Anibamine, a novel pyridine quaternary alkaloid recently isolated from Aniba sp., has been found to effectively bind to the chemokine receptor CCR5 with an IC50 at 1 μM in competition with 125I-gp120, an HIV viral envelope protein binding to CCR5 with high affinity. Since CCR5, a G-protein-coupled receptor, is an essential co-receptor for the human immunodeficiency virus type I (HIV-1) entry to host cells, a CCR5 antagonist that inhibits the cellular entry of HIV-1 provides a new therapy choi...
Padi, Satyanarayana S V; Shi, Xiang Q; Zhao, Yuan Q; Ruff, Michael R; Baichoo, Noel; Pert, Candace B; Zhang, Ji
Chemokine signaling is important in neuropathic pain, with microglial cells expressing CCR2 playing a well-established key role. DAPTA, a HIV gp120-derived CCR5 entry inhibitor, has been shown to inhibit CCR5-mediated monocyte migration and to attenuate neuroinflammation. We report here that as a stabilized analog of DAPTA, the short peptide RAP-103 exhibits potent antagonism for both CCR2 (half maximal inhibitory concentration [IC50] 4.2 pM) and CCR5 (IC50 0.18 pM) in monocyte chemotaxis. Oral administration of RAP-103 (0.05-1 mg/kg) for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia after partial ligation of the sciatic nerve in rats. Administered from days 8 to 12, RAP-103 (0.2-1 mg/kg) reverses already established hypersensitivity. RAP-103 relieves behavioral hypersensitivity, probably through either or both CCR2 and CCR5 blockade, because by using genetically deficient animals, we demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain. Moreover, RAP-103 is able to reduce spinal microglial activation and monocyte infiltration, and to inhibit inflammatory responses evoked by peripheral nerve injury that cause chronic pain. Our findings suggest that targeting CCR2/CCR5 should provide greater efficacy than targeting CCR2 or CCR5 alone, and that dual CCR2/CCR5 antagonist RAP-103 has the potential for broad clinical use in neuropathic pain treatment.
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.......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 designing...
Tsagkias, M.; Weerkamp, W.; de Rijke, M.
Online news agents provide commenting facilities for their readers to express their opinions or sentiments with regards to news stories. The number of user supplied comments on a news article may be indicative of its importance, interestingness, or impact. We explore the news comments space, and com
Nichols, John Spicer
The establishment of a regional news agency for Latin America to improve the balance of news flow and increase the transmission of news more applicable to regional problems has often been proposed. Despite wide acceptance of the concept, the birth of the Third World's first regional news agency, Agencia Latinoamericana de Informacion (LATIN), has…
... 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...
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...... perspective, through the lens of cognition and pragmatics, revealing the role played by cultural knowledge in comprehension and the underlying relationship between a text and its intended audience. It is argued that recipients ‘problematise’ the news texts, a process by which the texts answer questions...... that take their roots in the cultural knowledge of the recipients....
Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda
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…
Falteisek, Lukáš; Cerný, Jan; Janštová, Vanda
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…
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
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 wh
Sellebjerg, F; Kristiansen, T B; Wittenhagen, P
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)....
Thiele, Stefanie; Steen, Anne; Jensen, Pia C;
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...
McFarlane, Delano J.; Elhadad, Noémie; Kukafka, Rita
An important task performed during the analysis of health news coverage is the identification of news articles that are related to a specific health topic (e.g. obesity). This is often done using a combination of keyword searching and manual encoding of news content. Statistical language models and their evaluation metric, perplexity, may help to automate this task. A perplexity study of obesity news was performed to evaluate perplexity as a measure of the similarity of news corpora to obesit...
Fleming, Mark D; Pinkus, Jack L; Fournier, Marcia V; Alexander, Sarah W; Tam, Carmen; Loda, Massimo; Sallan, Stephen E; Nichols, Kim E; Carpentieri, David F; Pinkus, Geraldine S; Rollins, Barrett J
It has been suggested that a switch in chemokine receptor expression underlies Langerhans cell migration from skin to lymphoid tissue. Activated cells are thought to down-regulate CCR6, whose ligand macrophage inflammatory protein-3 alpha (MIP-3 alpha)/CCL20 is expressed in skin, and up-regulate CCR7, whose ligands are in lymphoid tissues. In Langerhans cell histiocytosis (LCH), pathologic Langerhans cells (LCs) accumulate in several tissues, including skin, bone, and lymphoid organs. We have examined 24 LCH cases and find that pathologic LCs expressed CCR6 and CCR7 coincidentally in all cases. Furthermore, MIP-3 alpha/CCL20 is expressed by keratinocytes in involved skin and by macrophages and osteoblasts in involved bone. Expression of CCR6 by pathologic LCs may contribute to their accumulation in nonlymphoid organs such as skin and bone, whereas CCR7 expression may direct them to lymphoid tissue. Histiocytes in Rosai-Dorfman disease and hemophagocytic syndrome also coexpressed CCR6 and CCR7, suggesting that this may be a general attribute of abnormal histiocytes.
Kramp, Birgit K; Megens, Remco T A; Sarabi, Alisina; Winkler, Sabine; Projahn, Delia; Weber, Christian; Koenen, Rory R; von Hundelshausen, Philipp
The chemokine CCL5 recruits monocytes into inflamed tissues by triggering primarily CCR1-mediated arrest on endothelial cells, whereas subsequent spreading is dominated by CCR5. The CCL5-induced arrest can be enhanced by heteromer formation with CXCL4. To identify mechanisms for receptor-specific functions, we employed CCL5 mutants and transfectants expressing receptor chimeras carrying transposed extracellular regions. Mutation of the basic 50s cluster of CCL5, a coordinative site for CCL5 surface presentation, reduced CCR5- but not CCR1-mediated arrest and transmigration. Impaired arrest was restored by exchanging the CCR5-N-terminus for that of CCR1, which supported arrest even without the 50s cluster, whereas mutation of the basic 40s cluster essential for proteoglycan binding of CCL5 could not be rescued. The enhancement of CCL5-induced arrest by CXCL4 was mediated by CCR1 requiring its third extracellular loop. The domain exchanges did not affect formation and co-localisation of receptor dimers, indicating a sensing role of the third extracellular loop for hetero-oligomers in an arrest microenvironment. Our data identify confined targetable regions of CCR1 specialised to facilitate CCL5-induced arrest and enhanced responsiveness to the CXCL4-CCL5 heteromer.
@@ Xinhua, China's biggest news wire service, began broadcasting English-language programs on its China Xinhua News Network Corp. (CNC) on July 1. CNC will soon go on to broadcast other programs in French, Spanish, Portuguese, Arabic and Russian. CNC TV itself, now broadcasting 24 hours a day, was inaugurated in December 2009 amid much fanfare as "an important move for Xinhua to enrich the agency's business sectors and embrace the multimedia world," said Xinhua President Li Congjun during its launch.
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: email@example.com. Sue: phone: 765/494-0823; fax: 765/494-0239; email: firstname.lastname@example.org. 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
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
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.
Muntinghe, Friso L. H.; Verduijn, Marion; Zuurman, Mike W.; Grootendorst, Diana C.; Carrero, Juan Jesus; Qureshi, Abdul Rashid; Luttropp, Karin; Nordfors, Louise; Lindholm, Bengt; Brandenburg, Vincent; Schalling, Martin; Stenvinkel, Peter; Boeschoten, Elisabeth W.; Krediet, Raymond T.; Navis, Gerjan; Dekker, Friedo W.
The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5 Delta 32) leads to deficiency of the receptor. We hypothesized that CCR5 Delta 32 modulates inflammation-driven mortality in patients with ESRD. We studied the inter
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...
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...
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 ...
Carlson, Marilyn; West, Richard
The Calculus Concept Readiness (CCR) instrument is based on the broad body of mathematics education research that has revealed major understandings, representational abilities, and reasoning abilities students need to construct in precalculus level courses to be successful in calculus. The CCR is a 25-item multiple-choice instrument, and the CCR taxonomy articulates what the CCR assesses. The methodology used to develop and validate the CCR is described and illustrated. Results from administering the CCR as a readiness examination in calculus are provided along with data to guide others in using the CCR as a readiness examination for beginning calculus.
Cornu, Tatjana I; Mussolino, Claudio; Bloom, Kristie; Cathomen, Toni
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.
Full Text Available Abstract Background The CCL2 chemokine is involved in promoting cancer angiogenesis, proliferation and metastasis by malignancies that express CCR2 receptor. Thus the CCL2/CCR2 axis is an attractive molecular target for anticancer drug development. Methods We have generated a novel fusion protein using GMCSF and an N-terminal truncated version of MCP1/CCL2 (6-76 [hereafter GMME1] and investigated its utility as a CCR2-specific tumoricidal agent. Results We found that distinct to full length CCL2 or its N-truncated derivative (CCL2 5-76, GMME1 bound to CCR2 on mouse lymphoma EG7, human multiple myeloma cell line U266, or murine and human medulloblastoma cell lines, and led to their death by apoptosis. We demonstrated that GMME1 specifically blocked CCR2-associated STAT3 phosphorylation and up-regulated pro-apoptotic BAX. Furthermore, GMME1 significantly inhibited EG7 tumor growth in C57BL/6 mice, and induced apoptosis of primary myeloma cells from patients. Conclusion Our data demonstrate that GMME1 is a fusokine with a potent, CCR2 receptor-mediated pro-apoptotic effect on tumor cells and could be exploited as a novel biological therapy for CCR2+ malignancies including lymphoid and central nervous system malignancies.
陈祥锦; 张茂泉; 张惠灏; 朱有志; 吴坤琳; 张德杰
目的 探讨三阴性乳腺癌(triple-negative breast cancer,TNBC)组织中CC族趋化因子受体4(cc chemokine receptor 4,CCR4)和CCR7的表达意义及其与临床病理特征和预后之间的相关性.方法 应用免疫组织化学染色SP法检测TNBC、HER-2过表达型乳腺癌、TNBC癌旁组织及乳腺良性肿瘤(3组,各38例)和管腔型乳腺癌组织(40例)中CCR4和CCR7的表达.结果 在TNBC组织中,CCR4和CCR7的表达率分别为47.4％ (18/38)和50％(19/38),与非TNBC组相比,差异有统计学意义(P值分别为0.001和0.004).CCR4表达与TNBC肿瘤直径(P=0.023)、腋窝淋巴结转移(P=0.006)、肿瘤分期(P=0.016)和远处转移(P=0.028)相关.Kaplan-Meier生存分析显示CCR4表达与TNBC患者总生存率(overall survival,OS)相关(P=0.018).CCR7表达和TNBC患者的腋窝淋巴结转移相关(P=0.038),而与TNBC患者无病生存率(disease free survival,DFS)和OS无关.多因素分析显示腋窝淋巴结转移是TNBC患者DFS的独立预测因素(P=0.025),而CCR4是TNBC患者OS的独立预测因素(P=0.022).结论 TNBC中CCR4和CCR7的表达与腋窝淋巴结转移相关；CCR4可作为TNBC患者预后的独立预测指标.%Objective To investigate the relationship between the expression of both CC chemokine receptor 4 (CCR4) and CCR7 and clinical pathology as well as prognosis in triple-negative breast cancer (TNBC). Methods The expression of CCR4 and CCR7 in TNBC, Her-2 over-expression breast cancer, TNBC paracancerous tissues and mammary gland benign tumor (38 cases each for the 3 groups) , and 40 cases of lumina breast cancer were assessed by immunohistochemical technology SP method. Results The positive rate of CCR4 and CCR7 in TNBC were 47. 4% (18/38) and 50% (19/38) , respectively. The difference between the expression of CCR4 and CCR7 in TNBC and that in non-TNBC showed a statistical significance (P = 0. 001 and 0. 004, respectively). The expression of CCR4 in TNBC was correlated with tumor size (P = 0. 023) , axilla
Matsuo, Kazuhiko; Koizumi, Keiichi; Fujita, Mitsugu; Morikawa, Toshio; Jo, Michiko; Shibahara, Naotoshi; Saiki, Ikuo; Yoshie, Osamu; Nakayama, Takashi
Chemokine receptors CCR3 and CCR4 are preferentially expressed by TH2 cells, mast cells, and/or eosinophils, all of which are involved in the pathogenesis of allergic diseases. Therefore, CCR3 and CCR4 have long been highlighted as potent therapeutic targets for allergic diseases. Japanese traditional herbal medicine Kampo consists of multiple crude drugs/herbs, which further consist of numerous chemical substances. Recent studies have demonstrated that such chemical substances appear to promising sources in the development of novel therapeutic agents. Based on these findings, we hypothesize that Kampo-related crude drugs/herbs would contain chemical substances that inhibit the cell migration mediated by CCR3 and/or CCR4. To test this hypothesis, we screened 80 crude drugs/herbs to identify candidate substances using chemotaxis assay. Among those tested, Ephedra Herb inhibited the chemotaxis mediated by both CCR3 and CCR4, Cornus Fruit inhibited that mediated by CCR3, and Rhubarb inhibited that mediated by CCR4. Furthermore, Ephedra Herb specifically inhibited the chemotaxis mediated by not only CCR3 and CCR4 but CCR8, all of which are selectively expressed by TH2 cells. This result led us to speculate that ephedrine, a major component of Ephedra Herb, would play a central role in the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8. However, ephedrine exhibited little effects on the chemotaxis. Therefore, we fractionated Ephedra Herb into four subfractions and examined the inhibitory effects of each subfraction. As the results, ethyl acetate-insoluble fraction exhibited the inhibitory effects on chemotaxis and calcium mobilization mediated by CCR3 and CCR4 most significantly. In contrast, chloroform-soluble fraction exhibited a weak inhibitory effect on the chemotaxis mediated by CCR8. Furthermore, maoto, one of the Kampo formulations containing Ephedra Herb, exhibited the inhibitory effects on the chemotaxis mediated by CCR3, CCR4, and CCR8
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.
Surya Rao Padmasri
Full Text Available Though potent anti-HIV therapy has spectacularly reduced the morbidity and mortality of human immunodeficiency virus (HIV-1 infection in the advanced countries, it continues to be associated with substantial toxicity, drug-drug interactions, difficulties in adherence, and abnormal cost. As a result, better effective, safe antiretroviral drugs and treatment strategies keep on to be pursued. In this process, CCR5 (chemokine receptor 5 inhibitors are a new class of antiretroviral drug used in the treatment of HIV. They are designed to prevent HIV infection of CD4 T-cells by blocking the CCR5. When the CCR5 receptor is unavailable, ′R5-tropic′ HIV (the variant of the virus that is common in earlier HIV infection cannot engage with a CD4 T-cell to infect the cell. In August 2007, the FDA approved the first chemokine (C-C motif CCR5 inhibitor, maraviroc, for treatment-experienced patients infected with R5-using virus. Studies from different cohort in regions, affected by clad B HIV-1, demonstrate that 81-88% of HIV-1 variants in treatment naïve patients are CCR5 tropic and that virtually all the remaining variants are dual/mixed tropic i.e., are able to utilize both CCR5 and CXCR4 coreceptors. In treatment experienced patients, 49−78% of the variants are purely CCR5 tropic, 22−48% are dual/mixed tropic, and 2-5% exclusively utilize CXCR4. A 32 bp deletion in the CCR5 gene, which results in a frame shift and truncation of the normal CCR5 protein, was identified in a few persons who had remained uninfected after exposure to CCR5 tropic HIV-1 virus. This allele is common in white of European origin, with prevalence near to 10%, but is absent among East Asian, American Indian, Tamil Indian, and African ethnic groups. HIV-infected individuals, who are heterozygous for CCR5 delta 32, have slower rates of disease progression. The currently available data supports the continuation of the development of CCR5 antagonists in different settings related
News headline translation is one of the most important types of news translation. As news headline is strongly purposeful, the translation of it must be achieved by some special methods. The history of news headline translation is almost as long as that of newspapers, but it has not been attached enough attention to. In the last twenty years, Chinese scholars of this field have paid much greater attention to news headline translation. Concerned studies of principles of news headline translation have also been made remarkable progress.
With the improvement of people's life, sports has become an indispensable part of our life, which promotes sports news. Besides, sports news is one of the most significant way to promote cultural communication and enhance mutual understanding. Thus, sports news has an increasing role in the communication between China and outside world due to its unique advantages. Therefore, sports news translation has great practical and theoretical significance in today's society. with the analysis on the function and characteristics of the sports news, This thesis studies the sports news translation and proposes some practical translation skills.
Lhasa-Nyingchi Railway StartsConstruction in 2014 The second extension of theQinghai-Tibet Railway, Lhasa-Nyingchi Railway connectingLhasa and Nyingchi Prefecture isnow at the feasibility study stagewith two designs going southwardand northward under discussion.The rail is going to be built in2014.
Kunkel, Eric J.; Boisvert, Judie; Murphy, Kristine; Vierra, Mark A.; Genovese, Mark C.; Wardlaw, Andrew J.; Greenberg, Harry B.; Hodge, Martin R.; Wu, Lijun; Butcher, Eugene C.; Campbell, James J.
Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4+ lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4+ populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue-infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4+ lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra-lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69+). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in α4β7 expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation. PMID:11786428
Monocytes participate critically in atherosclerosis. There are 2 major subsets expressing different chemokine receptor patterns: CCR2+CX3CR1+Ly-6Chi and CCR2–CX3CR1++Ly-6Clo monocytes. Both C-C motif chemokine receptor 2 (CCR2) and C-X3-C motif chemokine receptor 1 (CX3CR1) are linked to progression of atherosclerotic plaques. Here, we analyzed mouse monocyte subsets in apoE-deficient mice and traced their differentiation and chemokine receptor usage as they accumulated within atherosclerotic...
Latinovic, Olga; Schneider, Kate; Szmacinski, Henryk; Lakowicz, Joseph R; Heredia, Alonso; Redfield, Robert R
The CCR5 chemokine receptor is crucial for human immunodeficiency virus type 1 (HIV-1) infection, acting as the principal coreceptor for HIV-1 entry and transmission and is thus an attractive target for antiviral therapy. Studies have suggested that CCR5 surface density and its conformational changes subsequent to virion engagement are rate limiting for entry, and consequently, infection. Not all CCR5 antibodies inhibit HIV-1 infection, suggesting a need for more potent reagents. Here we evaluated full length single chain (FLSC) IgG1, a novel IgG-CD4-gp120(BAL) fusion protein with several characteristics that make it an attractive candidate for treatment of HIV-1 infections, including bivalency and a potentially increased serum half-life over FLSC, the parental molecule. FLSC IgG1 binds two domains on CCR5, the N-terminus and the second extracellular loop, lowering the levels of available CCR5 viral attachment sites. Furthermore, FLSC IgG1 synergizes with Maraviroc (MVC), the only licensed CCR5 antagonist. In this study, we used both microscopy and functional assays to address the mechanistic aspects of the interactions of FLSC IgG1 and MVC in the context of CCR5 conformational changes and viral infection. We used a novel stochastic optical reconstruction microscopy (STORM), based on high resolution localization of photoswitchable dyes to visualize direct contacts between FLSC IgG1 and CCR5. We compared viral entry inhibition by FLSC IgG1 with that of other CCR5 blockers and showed FLSC IgG1 to be the most potent. We also showed that lower CCR5 surface densities in HIV-1 infected primary cells result in lower FLSC IgG1 EC50 values. In addition, CCR5 binding by FLSC IgG1, but not CCR5 Ab 2D7, was significantly increased when cells were treated with MVC, suggesting MVC allosterically increases exposure of the FLSC IgG1 binding site. These data have implications for future antiviral therapy development.
Sasaki, Soichiro; Baba, Tomohisa; Nishimura, Tatsunori; Hayakawa, Yoshihiro; Hashimoto, Shin-Ichi; Gotoh, Noriko; Mukaida, Naofumi
From a murine breast cancer cell line, 4T1, we established a subclone, 4T1.3, which consistently metastasizes to bone upon its injection into the mammary fat pad. 4T1.3 clone exhibited similar proliferation rate and migration capacity as the parental clone. However, the intra-bone injection of 4T1.3 clone caused larger tumors than that of the parental cells, accompanied with increases in fibroblast, but not osteoclast or osteoblast numbers. 4T1.3 clone displayed an enhanced expression of a chemokine, CCL4, but not its specific receptor, CCR5. CCL4 shRNA-transfection of 4T1.3 clone had few effects on its in vitro properties, but reduced the tumorigenicity arising from the intra-bone injection. Moreover, intra-bone injection of 4T1.3 clone caused smaller tumors in mice deficient in CCR5 or those receiving CCR5 antagonist than in wild-type mice. The reduced tumor formation was associated with attenuated accumulation of CCR5-positive fibroblasts expressing connective tissue growth factor (CTGF)/CCN2. Tumor cell-derived CCL4 could induce fibroblasts to express CTGF/CCN2, which could support 4T1.3 clone proliferation under hypoxic culture conditions. Thus, the CCL4-CCR5 axis can contribute to breast cancer metastasis to bone by mediating the interaction between cancer cells and fibroblasts in bone cavity.
The economy principle of language obtained full manifestation in news English. This paper presents major ways in which people make news English economic, i.e. using short words, abbreviations, affixes, compounds and words with extended meanings and conversions.
Schrøder, Kim Christian; Steeg Larsen, Bent
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...
Swart, Joëlle; Peters, Chris; Broersma, Marcel
distinct news media repertoires are identified: 1) regionally-oriented 2) background-oriented 3) digital 4) laid-back and 5) nationally-oriented news use. Our findings indicate that users do not always use what they prefer, nor do they prefer what they use. Moreover, the boundaries they draw between news...... 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...... to each other to gain a fuller understanding of what news consumption entails in this rapidly changing media landscape....
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
English is used more than any other languages, so all of us should get a good command of it in order to be more competitive in this society. There're many ways to master this language, but through reading English language newspaper, with which we have so much contact everyday, is obviously more convenient and interesting. English language newspaper contain several parts, the features of each of them will be analyzed in this thesis together with a specific piece of news. Furthermore, some effective methods of reading and understanding English language news will be proposed.
Platt, Emily J; Durnin, James P; Kabat, David
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.
R. Berro; P.J. Klasse; D. Lascano; A. Flegler; K.A. Nagashima; R.W. Sanders; T.P. Sakmar; T.J. Hope; J.P. Moore
Resistance to small-molecule CCR5 inhibitors arises when HIV-1 variants acquire the ability to use inhibitor-bound CCR5 while still recognizing free CCR5. Two isolates, CC101.19 and D1/85.16, became resistant via four substitutions in the gp120 V3 region and three in the gp41 fusion peptide (FP), re
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, I show that issue characteristics and the selected news frame can determine whether and how emotions are elicited. Further, I provide evidence that affective news framing effects can arise as the r...
INTRODUCTION As English teachers, we have devoted a lot of time to the teaching of listening comprehension using radio broadcasts. We began by using VOA news in special English with freshmen and a mixture of news in special English and standard news broadcasts with sophomores. Later BBC news was used. We accumulated a considerable amount of experience and did some research into the design of listening comprehension exercises. This article discusses how listening ability may be improved by using such broadcasts.
This essay mainly studies the linguistic features of News English on stylistics.The study is made mainly on three aspects of News English.They are lexical features.sentence features and grammar features of News English.Through the study we find that News English,as a distinctive and new language.has its own lin-guistic features in words, sentences and grammar.
Gray Ian C
Full Text Available Abstract Background Several lines of evidence support a role for CCL2 (monocyte chemotactic protein-1 and its receptor CCR2 in the development of atherosclerosis. The aim of the present study was to determine the association of the CCR2 Val64Ile polymorphism with the development of coronary artery disease in the WOSCOPS study sample set. Findings A total of 443 cases and 1003 controls from the West of Scotland Coronary Prevention Study (WOSCOPS were genotyped for the Val64Ile polymorphism in the CCR2 gene. Genotype frequencies were compared between cases and controls. The CCR2 Val64Ile polymorphism was found not to be associated with coronary events in this study population (odds ratio 1.15, 95% CI 0.82-1.61, p = 0.41. Conclusions This case-control study does not support an association of the CCR2 Val64Ile polymorphism with coronary artery disease in the WOSCOPS sample set and does not confirm a possible protective role for CCR2 Val64Ile in the development of coronary artery disease.
Tang, Chengcheng; Zhang, Quanjun; Li, Xiaoping; Fan, Nana; Yang, Yi; Quan, Longquan; Lai, Liangxue
The lack of suitable animal model for HIV-1 infection has become a bottleneck for the development of AIDS vaccines and drugs. Wild-type rabbits can be infected by HIV-1 persistently and HIV-1 can be efficiently replicated resulting in syncytia in rabbit cell line co-expressing human CD4 and CCR5.Therefore, a rabbit highly expressing human CD4 and CCR5 may be an ideal animal model for AIDS disease study. In the present report, by using the efficient gene targeting technology, transcription activator-like effector nuclease (TALEN), we explored the feasibility of generating a HIV-1 model by knocking in human CD4 and CCR5 into rabbit genome. First we constructed two TALEN vectors targeting rabbit CCR5 gene and a vector with homologous arms. TALEN mRNAs and donor DNA were then co-injected into fertilized oocytes. After 3?5 days, 24 embryos were collected and used to conduct mutation analysis with PCR and sequencing. All the 24 embryos were detected with CCR5 knockouts and 5 were human CD4 and CCR5 knockins. Our results laid a foundation for establishing a new animal model for the study of AIDS.
Pardis C Sabeti
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.
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.
Tsagkias, M.; de Rijke, M.; Weerkamp, W.
Much of what is discussed in social media is inspired by events in the news and, vice versa, social media provide us with a handle on the impact of news events. We address the following linking task: given a news article, find social media utterances that implicitly reference it. We follow a three-s
D.E. Allen (David); M.J. McAleer (Michael); A.K. Singh (Abhay)
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 increas
Smit, Gerard; Haan, Yael de; Buijs, Laura; Bakker, Piet
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 qu
Reinhardt, Annika; Ravens, Sarina; Fleige, Henrike; Haas, Jan D; Oberdörfer, Linda; Łyszkiewicz, Marcin; Förster, Reinhold; Prinz, Immo
αβ T-cell development and selection proceed while thymocytes successively migrate through distinct regions of the thymus. For γδ T cells, the interplay of intrathymic migration and cell differentiation is less well understood. Here, we crossed C-C chemokine receptor (CCR)7-deficient (Ccr7(-/-) ) and CCR9-deficient mice (Ccr9(-/-) ) to mice with a TcrdH2BeGFP reporter background to investigate the impact of thymic localization on γδ T-cell development. γδ T-cell frequencies and numbers were decreased in CCR7-deficient and increased in CCR9-deficient mice. Transfer of CCR7- or CCR9-deficient BM into irradiated C57BL/6 WT recipients reproduced these phenotypes, pointing toward cell-intrinsic migration defects. Monitoring recent thymic emigrants by intrathymic labeling allowed us to identify decreased thymic γδ T-cell output in CCR7-deficient mice. In vitro, CCR7-deficient precursors showed normal γδ T-cell development. Immunohistology revealed that CCR7 and CCR9 expression was important for γδ T-cell localization within thymic medulla or cortex, respectively. However, γδ T-cell motility was unaltered in CCR7- or CCR9-deficient thymi. Together, our results suggest that proper intrathymic localization is important for normal γδ T-cell development.
Full Text Available Chemokine receptors are G protein-coupled receptors that contain seven transmembrane domains. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, and furthermore, targeting both CCR2 and CCR5 can be a useful strategy. Owing to the importance of these receptors, information regarding the binding site is of prime importance. Structural studies have been hampered due to the lack of X-ray crystal structures, and templates with close homologs for comparative modeling. Most of the previous models were based on the bovine rhodopsin and β2-adrenergic receptor. In this study, based on a closer homolog with higher resolution (CXCR4, PDB code: 3ODU 2.5 Å, we constructed three-dimensional models. The main aim of this study was to provide relevant information on binding sites of these receptors. Molecular dynamics simulation was done to refine the homology models and PROCHECK results indicated that the models were reasonable. Here, binding poses were checked with some established inhibitors of high pharmaceutical importance against the modeled receptors. Analysis of interaction modes gave an integrated interpretation with detailed structural information. The binding poses confirmed that the acidic residues Glu291 (CCR2 and Glu283 (CCR5 are important, and we also found some additional residues. Comparisons of binding sites of CCR2/CCR5 were done sequentially and also by docking a potent dual antagonist. Our results can be a starting point for further structure-based drug design.
Full Text Available Abstract Background Malaria afflicts 300–500 million people causing over 1 million deaths globally per year. The immunopathogenesis of malaria is mediated partly by co mplex cellular and immunomodulator interactions involving co-regulators such as cytokines and adhesion molecules. However, the role of chemokines and their receptors in malaria immunopathology remains unclear. RANTES (Regulated on Activation Normal T-Cell Expressed and Secreted is a chemokine involved in the generation of inflammatory infiltrates. Recent studies indicate that the degradation of cell-cell junctions, blood-brain barrier dysfunction, recruitment of leukocytes and Plasmodium-infected erythrocytes into and occlusion of microvessels relevant to malaria pathogenesis are associated with RANTES expression. Additionally, activated lymphocytes, platelets and endothelial cells release large quantities of RANTES, thus suggesting a unique role for RANTES in the generation and maintenance of the malaria-induced inflammatory response. The hypothesis of this study is that RANTES and its corresponding receptors (CCR1, CCR3 and CCR5 modulate malaria immunopathogenesis. A murine malaria model was utilized to evaluate the role of this chemokine and its receptors in malaria. Methods The alterations in immunomodulator gene expression in brains of Plasmodium yoelii 17XL-infected mice was analysed using cDNA microarray screening, followed by a temporal comparison of mRNA and protein expression of RANTES and its corresponding receptors by qRT-PCR and Western blot analysis, respectively. Plasma RANTES levels was determined by ELISA and ultrastructural studies of brain sections from infected and uninfected mice was conducted. Results RANTES (p Conclusion The upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during P. yoelii 17XL malaria.
王晓桃; 林文远; 陈蓓莉; 刘冯; 吴洪; 刘健; 莫东华
目的:探讨趋化因子受体CCR1和CCR5在多发性骨髓瘤(MM)患者骨髓单个核细胞(BMMNC)中的表达及临床意义.方法:半定量RT-PCR检测28例MM患者BMMNC中的CCR1和CCR5 mRNA水平.结果:46.4%患者同时表达CCR1、CCR5,17.86%患者仅表达CCR1,7.1%患者仅表达CCR5;骨质破坏＞2级患者的CCR1、CCR5相对灰度值明显高于骨质破坏≤2级的患者(P＜0.05);高度危险组中的CCR1、CCR5 相对灰度值明显高于中、低度危险组(P＜0.05),而中、低度危险组中的CCR1、CCR5相对灰度值无显著性差异(P＞0.05).结论:大部分MM 患者均表达CCR1和CCR5受体,监测CCR1、CCR5两种受体在MM中BMMNC的表达可以作为评价患者骨质破坏及预后的指标.
Desmetz, Caroline; Lin, Yea-Lih; Mettling, Clément; Portalès, Pierre; Rabesandratana, Herisoa; Clot, Jacques; Corbeau, Pierre
We have shown that the intensity of expression of the C-C chemokine receptor CCR5 at the single CD4(+) cell level strongly determines the efficiency of its function as a coreceptor for human immunodeficiency virus type 1. By analogy, we examined if the number of CCR5 molecules at the cell surface might determine its chemotactic response to CCR5 ligands. To test this hypothesis, we measured by flow cytometry the migration of primary human T cells towards the CCR5-binding chemokine CCL5 in vitro. First, we observed a dose-dependent blockage of this migration exerted by an anti-CCR5 monoclonal antibody. Second, we sorted peripheral blood mononuclear cells into five subpopulations expressing various cell surface CCR5 densities, and observed a correlation between the intensity of migration towards CCL5 and the level of CCR5 expression on these subpopulations. Third, we transduced CCR5(+) peripheral blood mononuclear cells with the CCR5 gene, and observed that the CCR5 over-expression induced an over-migration towards CCL5. Finally, we observed in healthy donors a correlation between the chemotactic response of peripheral blood CD8(+) T cell to CCL5 and their level of surface CCR5 expression. T-cell surface CCR5 density, which is constant over time for a given individual, but varies drastically among individuals, might therefore be an important personal determinant of T-cell migration in many biological situations where CCR5-binding chemokines play a role, such as graft rejection, T helper 1-mediated auto-immune diseases, and infectious diseases involving CCR5. Moreover, our data highlight the therapeutic potential of CCR5 antagonists in these situations.
Nielsen, Carol; Sassi, Brenda
Fourth graders in the Meroby School, Mexico, Maine, produce a weekly news program that is transmitted to all classrooms via closed circuit television. The classroom teacher is in charge of day-to-day preparation, working on the writing and the necessary skills with students. Teachers and students use their creativity to come up with new…
... Talk to Your Child About the News How Media Use Affects Your Child Helping Kids Deal With Bullies Gun Safety Posttraumatic Stress Disorder (PTSD) Healthy Habits for TV, Video Games, and the Internet Word! Violence Disasters Gun Safety Terrorism Someone at School Has ...
Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5−/−) mice. CCR5−/− and CCR5+/+ (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG3...
Nizamani, Sarwat; Memon, Nasrullah
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....
... page: https://medlineplus.gov/news/fullstory_161325.html Zika Connection to Rare Nerve Disorder Bolstered by Study ... has developed the strongest evidence to date that Zika virus can cause a rare nerve disorder called ...
Full Text Available Given the intense emphasis on weather forecast news in the US media, this study will approach the news as “affective mediated phenomenon” in a search for the problems which motivates practices or depletions. Through the ontological readings of ‘affect’ in the recent literature on “affective turn”, it aims to open up a new platform to analyze the fundamentals of relationality within televised and online weather forecasting and their extension in the society. I will focus on the Facebook group “Stop the Weather Channel from naming Winter Storms” which was created as a resistance to the everyday production of affective threat-values of The Weather Channel (TWC’s naming of storms. I will analyze both the shared images from TV (via YouTube videos and user comments on them utilizing Brian Massumi’s notion of “affective facts” and Anna Gibbs’ notion of “affect-contagion”. I will argue that, weather news produces affective registers which trigger continuous processes of re-making of the bodies as if it is a real situation. Thus, through the affective reality of anticipated alternatives created by weather news, performative threat-value of the thought-signs increases. I will show instances of mimetic relations between the bodies as anxiety formation through the portrayals of practices of emptying supermarkets, showing “signs” through visualized narration of cloud movements, and live-connections to the “scene”. Media’s emphasis on faces, values and rhythms of resonance with the portrayed bodies in anxiety from the previous storms works as an activation contour of affect-contagion. Weather news produces a form of subjectivity through affective mediations of technical means which amplifies audiences.
Hwang, Chul Ju; Park, Mi Hee; Hwang, Jae Yeon; Kim, Ju Hwan; Yun, Na Young; Oh, Sang Yeon; Song, Ju Kyung; Seo, Hyun Ok; Kim, Yun-Bae; Hwang, Dae Yeon; Oh, Ki-Wan; Han, Sang-Bae; Hong, Jin Tae
Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-Ä¸B activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment.
Yuan, Jing; Ren, Han-Yun; Shi, Yong-Jin; Liu, Wei
Blockade of CC chemokine receptor 5 (CCR5) by maraviroc may induce immunological changes independent of its antiviral effects and may have immunoregulation properties. This study was designed to determine the effects of blocking CCR5 on human activated T cells in vitro and investigate the potential immunological mechanisms. Human CD3+ T cells were purified from peripheral blood mononuclear cells and then activated by cytokines. We tested the surface expressions and relative messenger RNA (mRNA) levels of CCR2, CCR5, CCR6, CCR7, and CXCR3, chemotaxis toward their cognate ligands, internalization of chemokine receptors, and production of cytokines. In conclusion, blocking CCR5 by maraviroc not only can block CCR5 and CCR2 internalization processes induced by CCL5 and CCL2, but also inhibit T cell chemotactic activities toward their cognate ligands, respectively. Moreover, blocking CCR5 with maraviroc at high doses tends to decrease the production of TNF-α and IFN-γ. In addition, there might be a form of cross talk between CCR5 and CCR2, and this may offer a novel immunological effect for blockade of CCR5.
Gu, Sun Mi; Park, Mi Hee; Yun, Hyung Mun; Han, Sang Bae; Oh, Ki Wan; Son, Dong Ju; Yun, Jae Suk; Hong, Jin Tae
Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5-/-) mice. CCR5-/- and CCR5+/+ (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5-/- mice than CCR5+/+ mice. Immune cells (CD3+, CD4+, CD8+, B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5-/- mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5-/- mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5-/- mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.
(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 Â£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
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...
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
Full Text Available While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a−/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a−/− mice. In the mdr1a−/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation.
陈琳玲; 张佳; 高汉林; 廖端芳; 李凯
Lau, Gloria; Labrecque, Jean; Metz, Markus; Vaz, Roy; Fricker, Simon P
The chemokine receptors CCR5 and CCR2b share 89% amino acid homology. CCR5 is a co-receptor for HIV and CCR5 antagonists have been investigated as inhibitors of HIV infection. We describe the use of two CCR5 antagonists, Schering-C (SCH-C), which is specific for CCR5, and TAK-779, a dual inhibitor of CCR5 and CCR2b, to probe the CCR5 inhibitor binding site using CCR5/CCR2b chimeric receptors. Compound inhibition in the different chimeras was assessed by inhibition of chemokine-induced calcium flux. SCH-C inhibited RANTES (regulated on activation, normal T cell expressed and secreted) (CCL5)-mediated calcium flux on CCR5 with an IC50 of 22.8 nM but was inactive against monocyte chemoattractant protein-1 (CCL2)-mediated calcium flux on CCR2b. However, SCH-C inhibited CCL2-induced calcium flux against a CCR5/CCR2b chimera consisting of transmembrane domains IV-VI of CCR5 with an IC50 of 55 nM. A sequence comparison of CCR5 and CCR2b identified a divergent amino acid sequence located at the junction of transmembrane domain V and second extracellular loop. Transfer of the CCR5 sequence KNFQTLKIV into CCR2b conferred SCH-C inhibition (IC50 of 122 nM) into the predominantly CCR2b chimera. Furthermore, a single substitution, R206I, conferred partial but significant inhibition (IC50 of 1023 nM) by SCH-C. These results show that a limited amino acid sequence is responsible for SCH-C specificity to CCR5, and we propose a model showing the interaction with CCR5 Ile(198).
... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY 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;...
Most students entering our introductory astronomy course for nonscience majors arrive not merely lacking scientific facts-they also have misconceptions about the nature of science, and many have a handicapping ``science anxiety'' (in addition to math anxiety). So I have added a ``current science'' requirement to our introductory course. Each student must compile a file of five astronomy news articles taken from readily available sources.
Colin, Philippe; Bénureau, Yann; Staropoli, Isabelle; Wang, Yongjin; Gonzalez, Nuria; Alcami, Jose; Hartley, Oliver; Brelot, Anne; Arenzana-Seisdedos, Fernando; Lagane, Bernard
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.
Lee, Dong Hun; Park, Mi Hee; Hwang, Chul Ju; Hwang, Jae Yeon; Yoon, Hae Suk; Yoon, Do Young; Hong, Jin Tae
C-C chemokine receptor 5 (CCR5) regulates leukocyte chemotaxis and activation, and its deficiency exacerbates development of nephritis. Therefore, we investigated the role of CCR5 during lipopolysaccharide (LPS)-induced acute kidney injury. CCR5-deficient (CCR5-/-) and wild-type (CCR5+/+) mice, both aged about 10 months, had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg). Compared with CCR5+/+ mice, CCR5-/- mice showed increased mortality and renal injury, including elevated creatinine and blood urea nitrogen levels, following LPS challenge. Compared to CCR5+/+ mice, CCR5-/- mice also exhibited greater increases in the serum concentrations of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β following LPS challenge. Furthermore, infiltration of macrophages and neutrophils, expression of intracellular adhesion molecule (ICAM)-1, and the number of apoptotic cells were more greatly increased by LPS treatment in CCR5-/- mice than in CCR5+/+ mice. The concentrations of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β were also significantly increased in the kidney of CCR5-/- mice after LPS challenge. Moreover, primary kidney cells from CCR5-/- mice showed greater increases in TNF-α production and p38 MAP kinase activation following treatment with LPS compared with that observed in the cells from CCR5+/+ mice. LPS-induced TNF-α production and apoptosis in the primary kidney cells from CCR5-/- mice were inhibited by treatment with p38 MAP kinase inhibitor. These results suggest that CCR5 deficiency increased the production of TNF-α following LPS treatment through increased activation of the p38 pathway in the kidney, resulting in renal apoptosis and leukocyte infiltration and led to exacerbation of LPS-induced acute kidney injury.
马斌芳; 孙质健; 赵洁; 魏金花; 程胖; 冯潇; 李臻
Berro, Reem; Yasmeen, Anila; Abrol, Ravinder; Trzaskowski, Bartosz; Abi-Habib, Sarya; Grunbeck, Amy; Lascano, Danny; Goddard, William A; Klasse, Per Johan; Sakmar, Thomas P; Moore, John P
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.
JIANG Pei-juan; LIN Qi-de; BAO Shi-min; ZHAO Ai-min; ZHANG Yu; XIAO Shi-jin
Background Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4+ T cells.Methods Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/J×DBN2 (SA group, n=14), the normal pregnant mouse model CBA/J×BALB/c (NP group, n=13), and normal non-pregnant CBA/J mice (NNP group, n=11). The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4+ T cells was measured by double-label flow cytometry (FCM) method.Results In peripheral blood, the SA group had significantly lower CCR3 expression (P 0.05). In spleen, the SA group expressed significantly lower CCR3 expression (P 0.05). In thymus, the SA group had significantly lower CCR3 expression (P 0.05). Compared with the NNP group, the SA group had higher CCR3 expression (P 0.05) between the two groups.Conclusion The abnormal expression of CCR3, CCR5 and CXCR3 on CD4+ T cells may play an important role in the pathogenesis of spontaneous abortion.
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...
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
Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V
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...
Full Text Available Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC gene (APCMIN/+ mice to generate APCMIN/+ mice with CCR6 knocked out (CCR6KO-APCMIN/+ mice. CCR6KO-APCMIN/+ mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APCMIN/+ also had normal sized spleens as compared to the enlarged spleens found in APCMIN/+ mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APCMIN/+ as compared to APCMIN/+ mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy.
Kling, J C; Darby, J; Körner, H
Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self-healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7(-/-) mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self-healing response, we adoptively transferred CCR7(+) (B6.WT) DCs into the site of infection of B6.CCR7(-/-) mice. Surprisingly, instead of healing the lesion, B6.CCR7(-/-) mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7(-/-) mice transferred with B6.CCR7(-/-) DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7(-/-) DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.
C.L. Hyde; A. MacInnes; F.A. Sanders; J.F. Thompson; R.A. Mazzarella; O. Faergeman; D.F. van Wijk; L. Wood; M. Lira; S.A. Paciga
Background-There is mounting evidence to suggest that chemokine receptor 5 (CCR5) plays an important role in the development and progression of atherosclerosis. A naturally occurring variant of the CCR5 gene CCR532, exists at allele frequencies of typically 10% in European populations and results in
Muntinghe, Friso L. H.; Gross, Sascha; Bakker, Stephan J. L.; Landman, Gijs W. D.; van der Harst, Pim; Bilo, Henk J. G.; Navis, Gerjan; Zuurman, Mike W.
Aims: To test whether the genetic variant CCR5 Delta 32 in the CC-chemokine receptor 5, which is known to lead to CCR5 deficiency, is associated with mortality in type 2 diabetes patients. Methods: We examined the effect of presence or absence of the CCR5 Delta 32 on overall and cardiovascular morta
Full Text Available Abstract Background The chemokine receptor CCR7 is a key organizer of the immune system. Gene targeting in mice revealed that Ccr7-deficient animals are severely impaired in the induction of central and peripheral tolerance. Due to these defects, Ccr7-deficient mice spontaneously develop multi-organ autoimmunity showing symptoms similar to those observed in humans suffering from connective tissue autoimmune diseases. However, it is unknown whether mutations of CCR7 are linked to autoimmunity in humans. Results DNA samples were collected from 160 patients suffering from connective tissue autoimmune disease (Sjogren's syndrome, n = 40; systemic lupus erythematosus, SLE, n = 20 and systemic sclerosis, n = 100 and 40 health subjects (n = 40. All participants in this study were of German descent. Samples were screened for single nucleotide polymorphisms (SNP by sequencing the coding region of the CCR7 gene as well asthe exon flaking intron sites and parts of the regions encoding for the 5'- and 3'-UTR. CCR7 variants were rare. We identified six different sequence variants, which occurred in heterozygosis. The identified SNP were observed at position -60 C/T (observed 1x, +6,476 A/G (7x, +6,555 C/T (15x, +6,560 C/T (6x, +10,440 A/G (3x and +11,475 C/A (1x. Four of these variants (+6,476 A/G, +6,555 C/T, +6,560 C/T and +10,440 A/G display allelic frequencies between 1% and 5 % and were present in both patients and control groups. The variants +6,476 A/G, +6,555 C/T, +6,560 C/T are located in the intron 2, while the +10,440 A/G variant corresponds to a silent mutation in exon 3. The variants -60 C/T and +11,475 C/A which are located at the 5'-UTR and 3-UTR respectively, display allelic frequencies below 1%. No correlation between these variants and the autoimmune diseases investigated could be observed. However, reporter gene expression assay demonstrated that the mutation at the -60 C/T position in homozygosis leads to reduced luciferase activity
Social media are revolutionizing the ways that people communicate and the ways they get their news. Traditional news outlets are in decline, and no subject area is declining faster than science news. Every day there are fewer professional science journalists working in traditional media. On the other hand, ever greater numbers of scientists, science enthusiasts, and online journalists are turning to blogs, podcasts, eBooks, twitter feeds, and social media sites like Facebook and Tumbler to spread news about science. I will present an overview of the state of science journalism and speculate on the likely directions it seems to be heading. I will also offer some general guidelines to help scientists understand what makes a good science news story, as well as suggesting ways that they can get their work in the news.
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
Exposed seronegative individuals (ES) with persistent high-risk sexual behavior may be less susceptible to human immunodeficiency virus type 1 (HIV-1) infection because they carry the chemokine receptor (CR) gene alleles CCR5 open reading frame (ORF) Δ32, CCR5 promoter −2459G, or CCR2 ORF 64I (CCR2-64I), all of which have been found to diminish HIV-1 infectivity and/or disease progression. To investigate this, we determined the haplotypes for these three genetic loci in 93 ES and 247 low-risk...
郭满盈; 罗媛烨; 陈扬; 熊春林
目的 探讨趋化因子受体CCR6及CCR7在乳腺癌组织中的表达及其意义.方法 用免疫组织化学方法检测45例乳腺癌及10例乳腺纤维腺瘤组织中趋化因子受体CCR6及CCR7的表达,并对原位癌及发生转移的癌组织CCR6及CCR7的表达率进行比较.结果 在乳腺癌组织上检测到趋化因子受体CCR6及CCR7的表达(表达率分别为35.6%和48.9%),其中发生转移的癌组织CCR6及CCR7的表达率分别为41.7%和55.6%,未发生转移的癌组织CCR6及CCR7的表达率分别为11.1%和22.2%,乳腺纤维腺瘤组织中未发现CCR6及CCR7的表达.结论 乳腺癌组织上有趋化因子受体CCR6及CCR7的表达,其表达可能在乳腺癌的发生、发展和转移中发挥作用.%Objective To explore the expression of chemokine receptor CCR6 and CCR7 in breast cancer tissue and its clinical significance.Methods Forty-five cases of breast cancer specimens and ten cases of breast fibroadenoma specimens were analyzed by immunohistochemical staining for CCR6 and CCR7 expression. The rates of CCR6 and CCR7 expression were compared between primary and metastastic breast cancer tissue.Results The expression of CCR6 and CCR7 was detected in breast cancer (the positive rates were 35.6 % and 48.9% respectively). The CCR6 and CCR7 expression rates in primary and metastastic breast cancer tissue were 11.1%, 22.2% and 41.7%, 55.6% respectively, while CCR6 and CCR7 were not detected in breast fibroadenoma specimens.Conclusion CCR6 and CCR7 express in human breast cancer tissue, and they may play an important role in the occurrence, development and metastasis of human breast cancer.
Christiansen, Connie Carøe
demonstrates that diaspora as an analytic term is indeed relevant for immigrants, leaving room for questions of multiple belonging with implications for everyday life. According to recent data, people with migrant experience tend to seek news very broadly. Extensive news media consumption, desire for more...... 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....
Crawford, Doreen; Corkin, Doris; Coad, Jane; Hollis, Rachel
Some parents are unhappy with the way news is broken to them. This article seeks to educate and inform the reflective practitioner on a series of communication strategies to enhance their skills. This is important because the way news is disclosed can affect the way news is accepted and the level of support the family will require. The importance of clarity, honesty and empathy is emphasised.
The Good News and Bad News about Supporting Maturity Concepts Suzanne Garcia, SEI ®CMM, CMMI, IDEAL, and Capability Maturity Model are registered by...AND SUBTITLE CMMI: The Good News and Bad News about Supporting Maturity Concepts 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Dimensional Assessment of Technology Maturity in Fairborn, OH on 9-11 May 2006. U.S. Government or Federal Rights License 14. ABSTRACT 15. SUBJECT TERMS
Ørsten, Mark; Allern, Sigurd
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....
This paper aims to explore the underlying ideologies as well as the relationship between news discoutse and ideology by analyzing a news report on Saddam Hussei's capture in New York Times from the perspective of critical discourse analysis.While making the analysis,this paper studies the details of linguistic features,trausitivity,modality and themstic choice which are based on the three metafuoctions of language proposed by Halliday in systemic-functional grammar, so as to reveal how news discourse is used by powerful groups to reinforce dominant ideologies.and to gain profound insights about the stance and attitude maintained in news reports.
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.
Ferreira-Fernandes, H; Santos, A C C; Motta, F J N; Canalle, R; Yoshioka, F K N; Burbano, R R; Rey, J A; da Silva, B B; Pinto, G R
Chemokines are low-molecular weight proteins that play a key role in inflammatory processes. Genomic variations in chemokine receptors are associated with the susceptibility to various diseases. Polymorphisms in chemokine receptor type 5 (CCR5)-Δ32 and CCR2-V64I are related to human immunodeficiency virus infection resistance, which has led to genetic association studies for several other diseases. Given the heterogeneous distribution of these polymorphisms in different global populations and within Brazilian populations, we analyzed the prevalence of CCR5-Δ32 and CCR2-V64I polymorphisms in a mixed population from northeastern Brazil. The study included 223 individuals from the general population of the city of Parnaíba, Piauí, who had a mean age of 73 years. Of these individuals, 37.2% were men and 62.8% were women. Polymorphisms were analyzed using DNA extracted from peripheral blood leukocytes by using polymerase chain reaction alone (CCR5-Δ32) or accompanied by restriction endonuclease digestion (CCR2-V64I). In both cases, the genotypes were determined using 8% polyacrylamide gel electrophoresis and silver nitrate staining. The population conformed to Hardy-Weinberg equilibrium for both the loci studied. No individuals were homozygous for allele-Δ32, which was present in 1.8% of the population, whereas allele-64I was present in 13.9% of the participants studied; 74.9% were homozygous for the wild-type allele, while 22.4 and 2.7% were heterozygous and homozygous for the mutant allele, respectively. Additional studies are needed to investigate the relationship between these polymorphisms and disease etiopathogenesis in reference populations.
"As a calendar event, ‘China Textile’ Publishing House together with China Textile News appraised and selected the ten major news of China’s textile industry in 2009 as the news of the year according to the subscriptionon on a public poll basis ."
@@ "As a calendar event,'China Textile' Publishing House together with China Textile News appraised and selected the ten major news of China's textile industry in 2009 as the news of the year according to the subscriptionon on a public poll basis ."
van Cauwenberge, A.; d'Haenens, L.; Beentjes, H.
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 differen
Zweemer, Annelien J M; Bunnik, Julia; Veenhuizen, Margo;
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......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...
In dieser Arbeit wurde ein Kollektiv von duktalen Adenokarzinomen des Pankreas hinsichtlich einer Expression der Chemokinrezeptoren CCR7 und CXCR4 sowie des CCR7-Liganden CCL21 untersucht. Es konnte ein Zusammenhang zwischen der lymphatischen Ausbreitung des Karzinoms und der CCR7-Expression sowie ein Zusammenhang zwischen der CXCR4-Expression und hohen klinischen Tumorstadien dargestellt werden. Weiterhin wird die Expression CCL21 in intra- und peritumoralen Lymphgefäßen sowie in entzündeten...
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Weaver, Gail Cohen
Draws on resources in the ERIC system to discuss the following aspects of student journalism: recognizing and gathering the news; interviewing news sources; writing clear, concise, and accurate news stories; and understanding journalism law and ethics. (KS)
News,as an important way of communication is playing a crucial role in the comprehensive development of our country ranging from fast economic expansion,giant leap in science and technology,and progress in every aspects of social life.There is no doubt that News translation,in its specific and special way serves as an effective tool in spreading all sorts of information to a larger base of readers as rapid as possible.The function of the News is the transmission of information covering great events happening both at home and abroad in a timely and accurate manner.The information structure and the main ThemeRheme structure functions belong to the language of discourse.As we know,English pays emphasis on hypotactic relations while Chinese pay more attention to paratactic relations.What is more,English is the subject-predominant language with subject-predicate pattern easy to identify while Chinese is the topic-predominant language with topic-comment patterns as its prototype.The paper selects a large number of news items covering a wide range of subjects from CCTV news channel website and the Xinhua net as the paper’s corpus,Through the comparative study of both English and Chinese at the level of sentence then to text,the paper is trying to analyze the similarities and dissimilarities of source language and target language in their conversion process.Meanwhile,this paper draws a new conclusion that Theme-Rheme structures help us find the semantic connections between source language and target language.The novel point is that this is a two-way communication,namely,not only is the target language in accordance with source language,but also the source language conforms to the habitual usage of target language,realizing the stylistic equivalence between two texts.In a sense,the study of Theme-Rheme structure provides a great boost to the News Translation.
Muntinghe, Friso L. H.; Abdulahad, Wayel H.; Huitema, Minke G.; Damman, Jeffrey; Seelen, Marc A.; Lems, Simon P. M.; Hepkema, Bouke G.; Navis, Gerjan; Westra, Johanna
Background: In patients with end stage renal disease (ESRD) we observed protection from inflammation-associated mortality in CCR5 Delta 32 carriers, leading to CCR5 deficiency, suggesting impact of CCR5 Delta 32 on inflammatory processes. Animal studies have shown that CCR5 deficiency is associated
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
We have recently demonstrated that the CCR5Δ32 protein interacts with CCR5 and CXCR4 and down-modulates their cell surface expression. We have also reported the absence of detectable expression of the truncated CCR5Δ32 protein in four out of six human immunodeficiency virus-infected (HIV+) CCR5−/− individuals. To explain the defect in protein expression in these samples, we cloned and sequenced the promoter regions of the six HIV+ individuals. We have identified several polymorphisms in the C...
Toda, Etsuko; Terashima, Yuya; Esaki, Kaori; Yoshinaga, Sosuke; Sugihara, Minoru; Kofuku, Yutaka; Shimada, Ichio; Suwa, Makiko; Kanegasaki, Shiro; Terasawa, Hiroaki; Matsushima, Kouji
Chemokine receptors mediate the migration of leucocytes during inflammation. The cytoplasmic protein FROUNT binds to chemokine receptors CCR2 [chemokine (C-C motif) receptor 2] and CCR5, and amplifies chemotactic signals in leucocytes. Although the interaction between FROUNT and chemokine receptors is important for accurate chemotaxis, the interaction mechanism has not been elucidated. In the present study we identified a 16-amino-acid sequence responsible for high-affinity binding of FROUNT at the membrane-proximal C-terminal intracellular region of CCR2 (CCR2 Pro-C) by yeast two-hybrid analysis. Synthesized peptides corresponding to the CCR2 Pro-C sequence directly interacted with FROUNT in vitro. CCR2 Pro-C was predicted to form an amphipathic helix structure. Residues on the hydrophobic side are completely conserved among FROUNT-binding receptors, suggesting that the hydrophobic side is the responsible element for FROUNT binding. The L316T mutation to the hydrophobic side of the predicted helix decreased the affinity for FROUNT. Co-immunoprecipitation assays revealed that the CCR2 L316T mutation diminished the interaction between FROUNT and full-length CCR2 in cells. Furthermore, this mutation impaired the ability of the receptor to mediate chemotaxis. These findings provide the first description of the functional binding element in helix 8 of CCR2 for the cytosolic regulator FROUNT that mediates chemotactic signalling.
Collart, Martine A; Panasenko, Olesya O
The Ccr4-Not complex is an essential multi-subunit protein complex that plays a fundamental role in eukaryotic mRNA metabolism and has a multitude of different roles that impact eukaryotic gene expression . It has a conserved core of three Not proteins, the Ccr4 protein, and two Ccr4 associated factors, Caf1 and Caf40. A fourth Not protein, Not4, is conserved, but is only a stable subunit of the complex in yeast. Certain subunits have been duplicated during evolution, with functional divergence, such as Not3 in yeast, and Ccr4 or Caf1 in human. However the complex includes only one homolog for each protein. In addition, species-specific subunits are part of the complex, such as Caf130 in yeast or Not10 and Not11 in human. Two conserved catalytic functions are associated with the complex, deadenylation and ubiquitination . The complex adopts an L-shaped structure, in which different modules are bound to a large Not1 scaffold protein. In this chapter we will summarize our current knowledge of the architecture of the complex and of the structure of its constituents.
Paulissen, Sandra M J; van Hamburg, Jan Piet; Dankers, Wendy; Lubberts, Erik
The IL-17A producing T-helper-17 (Th17) cell population plays a major role in rheumatoid arthritis (RA) pathogenesis and has gained wide interest as treatment target. IL-17A expressing Th cells are characterized by the expression of the chemokine receptor CCR6 and the transcription factor RORC. In RA, CCR6+ Th cells were identified in peripheral blood, synovial fluid and inflamed synovial tissue. CCR6+ Th cells might drive the progression of an early inflammation towards a persistent arthritis. The CCR6+ Th cell population is heterogeneous and several subpopulations can be distinguished, including Th17, Th22, Th17.1 (also called non-classic Th1 cells), and unclassified or intermediate populations. Interestingly, some of these populations produce low levels of IL-17A but are still very pathogenic. Furthermore, the CCR6+ Th cells phenotype is unstable and plasticity exists between CCR6+ Th cells and T-regulatory (Treg) cells and within the CCR6+ Th cell subpopulations. In this review, characteristics of the different CCR6+ Th cell populations, their plasticity, and their potential impact on rheumatoid arthritis are discussed. Moreover, current approaches to target CCR6+ Th cells and future directions of research to find specific CCR6+ Th cell targets in the treatment of patients with RA and other CCR6+ Th cell mediated autoimmune diseases are highlighted.
Shi, Jie-Yi; Duan, Meng; Sun, Qi-Man; Yang, Liuxiao; Wang, Zhi-Chao; Mynbaev, Ospan A; He, Yi-Feng; Wang, Ling-Yan; Zhou, Jian; Tang, Qi-Qun; Cao, Ya; Fan, Jia; Wang, Xiao-Ying; Gao, Qiang
Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7(+) cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7(+) mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7(+) cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7(+) cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7(+) mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P CCR7(+) mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P CCR7(+) mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7(+) mononuclear cells featured a naive Treg-like phenotype (CD45RA(+)CD25(+)FOXP3(+)) and possessed tumor-promoting potential by producing TGF-β1. Moreover, CCR7(+) cells were also composed of several immunocytes, a third of which were CD8(+) T cells. CCR7(+) Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1.
Mencarelli, Andrea; Cipriani, Sabrina; Francisci, Daniela; Santucci, Luca; Baldelli, Franco; Distrutti, Eleonora; Fiorucci, Stefano
Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1α and β and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5(-/-) mice or adoptive transfer of splenic naïve CD4(+) T-cells from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+) leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.
Fabech, Sidsel Grøn
and newsmagazines have long been said to hold the power to define and represent national culture and identity. With the increasing globalization of cultures and the following need to redefine and negotiate national identity, the function of media as carrier and creator of identity seems to be reinforced. It is my...... aim to discuss how news media establish themselves as representatives of a certain national identity and narrative and are positioned in the national media landscape according to this. This paper raises the questions: Do national identity constructions need their “own” national media in order...
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
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.
In this work, we reveal the structure of global news coverage of disasters and its determinants by using a large-scale news coverage dataset collected by the GDELT (Global Data on Events, Location, and Tone) project that monitors news media in over 100 languages from the whole world. Significant variables in our hierarchical (mixed-effect) regression model, such as the number of population, the political stability, the damage, and more, are well aligned with a series of previous research. Yet, strong regionalism we found in news geography highlights the necessity of the comprehensive dataset for the study of global news coverage.
Hayasaka, Haruko; Kobayashi, Daichi; Yoshimura, Hiromi; Nakayama, Emi E; Shioda, Tatsuo; Miyasaka, Masayuki
During human immunodeficiency virus (HIV) infection, enhanced migration of infected cells to lymph nodes leads to efficient propagation of HIV-1. The selective chemokine receptors, including CXCR4 and CCR7, may play a role in this process, yet the viral factors regulating chemokine-dependent T cell migration remain relatively unclear. The functional cooperation between the CXCR4 ligand chemokine CXCL12 and the CCR7 ligand chemokines CCL19 and CCL21 enhances CCR7-dependent T cell motility in vitro as well as cell trafficking into the lymph nodes in vivo. In this study, we report that a recombinant form of a viral CXCR4 ligand, X4-tropic HIV-1 gp120, enhanced the CD4 T cell response to CCR7 ligands in a manner dependent on CXCR4 and CD4, and that this effect was recapitulated by HIV-1 virions. HIV-1 gp120 significantly enhanced CCR7-dependent CD4 T cell migration from the footpad of mice to the draining lymph nodes in in vivo transfer experiments. We also demonstrated that CXCR4 expression is required for stable CCR7 expression on the CD4 T cell surface, whereas CXCR4 signaling facilitated CCR7 ligand binding to the cell surface and increased the level of CCR7 homo- as well as CXCR4/CCR7 hetero-oligomers without affecting CCR7 expression levels. Our findings indicate that HIV-evoked CXCR4 signaling promotes CCR7-dependent CD4 T cell migration by up-regulating CCR7 function, which is likely to be induced by increased formation of CCR7 homo- and CXCR4/CCR7 hetero-oligomers on the surface of CD4 T cells.
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
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...
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,
Haroldsen, Edwin O.; Blake, Reed H.
In the traditional Turkish village, the coffee house acts as a modern-day parish pump in news transmission. Within the coffee house, there is evidence of a two-step flow of communication. The role of the influential person in this study is the same as that in other studies: as a mediator and interpreter of news. In social characteristics, however,…
Wiley, Gale F.
Presents description of local-area network of personal computers installed in the Broadcast News Laboratory at the University of Texas at Austin to help produce and teach broadcast news. Highlights include development and design of the system, software and hardware considerations, and the use of tutorials for writing and technical concepts. (LRW)
Altheide, David L.
A three-year research project, including more than one year in a network affiliate station, provided the material for an analysis of current practices in television news programming. Based on the thesis that the organization of news encourages the oversimplification of events, this analysis traces the foundation of the bias called the "news…
Ashley, Seth; Maksl, Adam; Craft, Stephanie
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,…
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...
Literacy Information and Communication System, 2011
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,…
Literature language and News language are two different language type,while,for attracting readers,writers more likely apply Literature language in News reports.This paper presents some comments on this phenomenon and make analysis,using examples to understand and comment on it.
Literature language and News language are two different language type, while, for attracting readers, writers more likely apply Literature language in News reports. This paper presents some comments on this phenomenon and make analysis, using examples to understand and comment on it.
Nizamani, Sarwat; Memon, Nasrullah
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...
V. Milea (Viorel)
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 messag
Literacy Information and Communication System, 2011
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…
Nansen, A; Marker, O; Bartholdy, C;
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...
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...
Rodell, Matthew; Beaudoing, Hiroko Kato; L'Ecuyer, Tristan; William, Olson
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.
This study examines stylistic features of the news story comments from major online news outlets and their possible ef-fects on the evolution of the English language. With a corpus composed of 34 examples drawn from renowned news sites such as The Washington Post, The Economist, Wall Street Journal, CNN and NBC, a detailed analysis on the stylistic features and effects of the news story comments has been conducted for the purpose of discovering possible links between a poster ’s linguistic behav-ior and his thought process. The result shows that interrogative, noun phrase and verb phrase are commonly used in news story comments by virtue of their slightly ostentatious nature. Rhetorical devices such as metaphor, simile and parataxis are frequently employed among comments. And the relationship between a poster’s educational background and his postings is also touched up-on at the end of this study.
collaboration and competition strategies. In addition, a novel method is developed that can be used to collect and analyze very large amounts of data on the resource exchanges that take place between news publishers and their business partners. The method allows for systematic mapping of the flows of resources...... leading American news publishers use to design their production networks. In the analysis, the activities carried out by and resource flows between a total of 1,356 business partners and news publishers in the American digital news publishing ecology are identified and visualized. In addition......News publishers in the industrialized world are experiencing a fundamental challenge to their business models because of the changing modes of consumption, competition, and production of their offerings that are associated with the emergence of the networked information society. The erosion...
<正>China’s Aluminium Processing Industry Profits Increased According to a report by China Nonferrous Metals Industry Association in the first quarter of this year, China’s aluminium processing industry realized some 40 per cent more profits compared that in the previous year, though the aluminium price increase has promoted the cost of production. This information is rather surprising to the industry analysts.
Chinese creativity blooms in Paris Following the event of"China in Paris·Unbounded Chinese Contemporary Creativity Night"show,which was listed in the official release schedule of Paris Fashion Week and held successfully in March
<正> Cable Industry Expected toConsume 1.7 Million Tons ofCopperAccording to industry experts,total turn over ofChina’s wire and cable industry will exceedRMB 160 billion by 2005,and the totalconsumption of copper is estimated to reach 1.7million tons.In 2002,the total output value ofChina’s cable industry was RMB 123.6 billionwhile the total sales revenue of the industrywas RMB 114.3 billion.2002 also saw aconsumption of 1.4 million tons of copper byChina’s cable industry,accounting for about 60percent of the total consumption of copper inthe domestic market.
"The twelfth ve-year plan" industrial transformation and upgrading plan released Textile industry was included in the key industries of reformRecently, the State Council officially released "industrial transformation and upgrading plan (2011-2015).
August PMI shows the shrinking of the export orders including textile industry The Purchasing Management Index of China (PMI) posted in September 1 shows that,the export orders index for August was 48.3%,dropped 2.1% from the previous month,which is the first time the figure fell (lower than 50%) since May 2009,
Textile & Clothes Orders Reach $4.56 Billon in Three Days Raw Material Prices Soaring Impact Canton Fair Leading by the cotton price, al-most all the textile and clothes raw material prices kept rising, which
<正>Policy, standard, regulation China mulling fuel tax to replace road tolls China’s top economic planning body is working with other organizations to handle the feasibility of setting a new fuel pricing mechanism and introducing fuel taxes to replace road tolls and cut oil prices.
<正>仪式·合作Ceremony&Cooperation海航集团捐赠中国公安民警英烈基金会和海地地震灾区HNA Donates to the Foundation for China Heroic Policeman Martyrs and Haiti Earthquake Disaster2010年1月18日10:00,海航集团向中国公安民警英烈基金会和海地地震灾区捐赠仪式在海航大厦四楼会议室举行。仪式开始前,全体人员起立默哀,向逝去的8名烈士和在地震中
Resources: Online schools video library GIREP Seminar: A seminar not a conference New Teaching Resource: Free living for teachers Space: NASA proposes MEER - Momentum Exchange Electrodynamic-Reboost Electronic Teaching Materials: Superconductivity motivates need for upper secondary curriculum subjects Gifted and Talented: Seminars seek challenges Space: Comet chasing Particle Physics: Playing with single electrons Physics on Stage: Teachers explore the meaning of life Physics on Stage: Greek national event Physics on Stage: Physics on the Slovak stage Physics on Stage: Clubbing in Germany Physics on Stage: The Sun's star performance Higher Education: Physics: so refreshing USA: Broadening the Base AAPT Summer Meeting: US teachers in good form Astronomy: High school astronomy in the Czech Republic Space: Express to Mars Particle Physics: Journey to the centre of the Earth? ASE 2004: Flight from the ASE Physics Songs: A powerful melody Teacher Training: European training looks for ideal model
<正>Chalco Enters Agreement with Vietnam on Bauxite Project During a State visit to Vietnam headed by China’s President Hu Jintao, Xiao Yaqing, Chairman and CEO of China Aluminium Corp. (Chalco) signed an agreement with his Vietnamese counterpart on the development of a bauxite project in Vietnam. Top officials of the two countries attended the signing ceremony in Hanoi. This project is known to be the largest one between the two countries up to present and it is taken by leaders of both countries as an important progress in promoting the bilateral relations in economy and trade.
摄影工作坊指导HIV感染者拍摄生活 南非摄影师Gideon Mendel从1993年开始追踪拍摄非洲的艾滋病患者，直到他觉得自己无法在这个题材上进行下去，难以举起相机。但是他对艾滋病的关注没有停止。
<正>New Zinc Smelter Started Running Out of Improved Market On July 1st, Huludao Nonferrous Metals Group Corp. launched its zinc production at a new smelter, and meanwhile another line with 50,000 tons annual capacity also restarted after five years of idling. The group’s zinc smelting capacity was originally designed for 130,000
Policy,standard,regulation China to enact a rule on inside car pollutants The first of its kind in China may come by the year end, an official at Beijing Municipal Labor Protection Research Institute said recently.
Townsend Observatory destroyed; BAA Lunar Section archives; Astro-Cymru; Royal star identified; Formation of Johannes Kepler Working Group; Tycho Brahe exhumed; Ancient observatory discovered in Iran...; ... and in Mexico; Calling all ex-occupants of interplanetary craft.
The list of eliminating backward production capability published Ministry of Industry and Information Technology (MIIT) declared enterprises’ list from 18 industries that to eliminate backward production
The consumer clothing prices rose 3.3% in January February 9,National Bureau of Statistics data show that in January,the national consumer price level rose by 4.5% year-on-year,consumer prices rose by 5.5%,prices of services rose by 2.2%; national consumer price level rose 1.5% month-on-month,consumer prices rose by 1.8%, prices of services rose by 0.8%. It is estimated that among the 4.5% year-on-year increase of comsumer prices of January, there are approximately 3.0% caused by the price
MOC Plans New Rule for Retail Business The access fee into supermarkets and department stores pushes flat prices and damage the interest of suppliers. Yao Jian, the spokenman of Ministry of Commerce said in a recent press conference that the MOC was drafting some rules to regulate this market
"12 five-year plan" Industrial Technology Innovation Plan released"12 five-year plan" Industrial Technology Innovation Plan was released by Ministry of Industry and Information Technology on November 14,clearing the objec-tives and priorities of industrial
The nation started temporary store up policy of cotton Notice of the Preplan of on the Startup of the Temporary Store Policy of Cotton2011was jointly announced on September 7,by Economic and Commercial Department of National Development and
Policy, standard, regulation Shanghai to enact local standards on small cars The technical condition document (DB31/T390-2007) takes effect on Dec 1, 2007. The standard is in fact a threshold for small cars sold in Shanghai.
<正> BriefingThe Administration recently issued a notice to initiate a new round campaign against illegal retrofit of automobiles. The move is aiming at matching the efforts of the 7 government departments concerned to fight against truck over-load campaign. The notice is attached by a name list of the approved auto makers and those not on the list should be closed this time, the notice read. The Administration is determined to basically put illegal retrofit to an end within three years.
"Made in China" Ad Campaign Calls for Global CooperationA 30-second TV commercial re-mains a hot topic in China nearly two weeks after four Chinese indus-try associations launched a "Made in China" ad campaign on the CNN
Textile industrial output value of the first 11 months increased27.5% The total production:from January to November,China’s35,900 large-scale(the main business income more than 20million Yuan)textile enterprises realized an industrial out-put value of4952.64billion Yuan,up27.5%,
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
Policy, standard, regulation The NDRC sets 15 preconditions for new energy vehicles Administrative rules for the production entry have appeared on the website of the NDRC. Fail of any one of the 15 preconditions may lead to the elimination of the total project.
Policy, standard, regulation The NDRC discontinues second-group failed passenger vehicle models The National Development and Reform Committee has recently announced the latest fuel consumption level data of passenger cars on its website.
PMI index down,the downward trend of economic growth continued China Federation of Logistics and Purchasing released November China’s Manufacturing Purchasing Managers Index(PMI) on December1,which indicated that the
China to Raise Export Tax Rebates for Textile,Garment Products China is raising tax rebates for certain exports to help producers cope with smaller profit margins as a result of slacking market demand,the yuan’s appreciation and rising production costs.
POLICY China set to restructure auto industry by mergers hina said it wanted to boost its auto industry by reducing the number of companies in the sector through mergers and promoting two or three carmakers to become the dominant players. The government's plans for auto industry reform were
The 3rd Textile Entrepreneurs Survey:Economic Situation Turns to Better,Confidence Returns To follow the situation of textile enterprises, and learn the confidence of entrepreneurs on their business, China Textile Entrepreneur Association
Policy, standard, regulationl Administration program for environmental protection during the 11th five-year collecting comments The State Environmental Protection Administration has recently issued the draft document for comments. The program is expected to form a framework and establish the policies for the period 2006-2010.
<正>Policy,standard,regulation New energy car purchasers to be granted 20 billionyuan subsidiesBoth the producers and users will enjoy the subsidiesthrough direct allowance and taxation cut,a seniorofficial at the Ministry of Finance told a forum recently
<正>Policy,standard,regulation China says to raise tax on big cars China’s cabinet agreed in principle to raise the consumption tax on cars with large engines to help save energy,the government said recently.
Radioactivity: Olympic Games: dirty and decaying? Awards: SciCast rewards the best in scientific short films Conference: Teachers conference is big in Boston Workshop: Experts and teachers mingle in Mexico Awards: Olympiad holds lavish ceremony Cinema: Indiana Jones has a skull full of physics Conference: ESERA announces Turkish delight for 2009 Forthcoming Events
T300 Carbon Fiber Technique Made Breakthrough Zhongfu Shenying Carbon Fiber&Key Equipment Program Completed CNTAC organized a technology achievement appraisal meeting in Lianyungang for the program of R&D of Annu
Policy, standard, regulationl China to formulate national standard for fuel cell powered vehiclesThe campaign has started in Shanghai where first two documents-vehicle term and safety requirement are expected to come in 2008.
<正>Policy, standard, regulation Chongqing enacts China’s first local rule to govern the natural gas vehicle industry The administrative method is due to take effect on July 1, 2008. The legal process took the local authorities 3 years.
IRELAND New courses for high-tech Ireland; SCIENCE YEAR Science Year launched with a jump; THE NETHERLANDS School science teachers face uncertainty; KOREA Embedding physics in a cultural context; TEACHING RESOURCES Teacher, get your hook; ICT RESOURCES Stock-take of ICT progress; INTERNET Teachers to test-drive new physics gateway; NEW ZEALAND Physics is valued in New Zealand; JAPAN Advancing Physics in Japan; HIGHER EDUCATION Networking works in Cologne; INSTITUTE MATTERS IoP demands a better deal for physics teachers; AUSTRALIA Physics numbers decline: educators blame the low impact curriculum; SCIENCE FOR THE PUBLIC More than sixty seconds in Glasgow; INTERNET A gift selection of papers from IoP; TEACHING STYLES I know what you did last summer;
Underwear Special Fund Established in China China’s f irst underwear technology fund, ZhengMintai China Knitting (Underwear) Fund is established re- cently. It is also the fi rst specail fund in the textile industry of China. This fund is supported by China
<正>Zinc Smelter Ordered to Stop On River Contamination Hazard Zinc production at China’s Shaoguan Smelter is called for a halt recently due to an accident which has led to the serious pollution to a river in Guangdong province, South China. Based on a report by the environmental authorities, a recent checkup found that the water running in the smelter area has increased cadmium contamination. Initial studies showed that the cadmium content came from the waste water discharged by the smelter during a period of equipment maintenance. This water contamination case is considered by the environmental control authorities as a serious pollution case in the area for breaking the related environmental protection laws and regulations.
Jack 8th China National Garment Brand Annual Awards announced March 25,Jack The 8th China National Garment Brand Annual Awards Presentation Ceremony held at the Beijing Century Theatre. 9 awards of Chinese clothing were unveiled,namely they are: brand style,innovation potential,quality,planning,marketing,public,value,achievements as well as other special awards such as: promote,support,clothing,manufacturing,commercial.
China Textile&Apparel Export Rebounds With the recovery of global economy,and the low base number of last year’s export,as well as the export product price rising droven by raw material price increase,the export of textile and apparel products turned to rebound in first half.
Textile Export Grew Fast, But Future Still Unclear According to the latest Customs data, the export of textile & garment kept stable growth from Jan. to May. The accumulated export in first five months
<正>China’s Export of Fabricated Aluminium Kept Growing According to China customs statistics, China’s export of fabricated aluminium in 2004 grew by 57.3 per cent or 157,000 tons year on year to reach 431,000 tons. Among the total export, aluminium plates and belts were 82,000 tons, up by 56.7 per cent year on year. Export of aluminium foil grew by 63.1 per cent to 75,000 tons and export of aluminium profile and rods grew by 57 per cent to 244,300 tons.
Meeting: Brecon hosts 'alternative-style' Education Group Conference Meeting: Schools' Physics Group meeting delivers valuable teaching update Saturn Mission: PPARC’s Saturn school resource goes online Funding: Grant scheme supports Einstein Year activities Meeting: Liverpool Teachers’ Conference revives enthusiasm for physics Loan Scheme: Moon samples loaned to schools Awards: Schoolnet rewards good use of ICT in learning Funding: PPARC provides cash for science projects Workshop: Experts in physics education research share knowledge at international event Bulgaria: Transit of Venus comes to town Conference: CERN weekend provides lessons in particle physics Summer School: Teachers receive the summer-school treatment
Wales: Dataloggers network teachers 11-16 Science: Educational magazines with the fun bits left in! Institute of Physics: Public Awareness of Physics Awards Events: TeachSpace 2001 Australia: Chemistry and Physics in Tasmanian Agriculture Resources: From out of this world, into your lab Nobel Prize: Nobel Prize in Physics, 2001 China: Physics education for the 21st century: avoiding a crisis Resources: The Royal Astronomical Society Forthcoming Events
4762 Products Enjoy Zero-tariff Treatment in Chinese MarketIn Summit on the Millennium Development Goals of UN, Chinese Government promised the zero-tariff treatment for the underdeveloped countries. From July 1st of 2010, about 4762 products from Bengal and other 31 underdeveloped countries could enjoy the zero-tariff treatment in Chinese market.
Physics on Stage: Physics on Stage focuses on life Women in Physics: DNA posters highlight the role of women Physics on Stage: Not just fair but better than ever Physics on Stage: Food inspires teaching of physics Physics on Stage: Powerful performances dispel the myth of boring physics Physics Songs: Physics inspires some of our readers to sing Physics on Stage: Awards recognize achievements of science teachers in Europe Curriculum: Japan tests Advancing Physics UK Assessment System: Assessment overhaul is overdue Future Physicists: Ambassadors are bringing physics alive Physics at work: Physics at work still going strong Teaching Teachers: US coalition helps new teachers Forthcoming Events
High-tech Prop up National Flag in Tian’anmen Square During the 60th National Day Ceremony,thousands of national flags are going to fly over the streets.They are all manufactured by an exclusive producer,Beijing Red Flag Co.,Ltd.
Cotton prices where to go after purchase and reserve end April,this year’s cotton purchasing and reserve work came to an end,the policy factors that support cotton prices weakened. For some time,how the cotton price will change has become the focus of widespread concern of the industry.
China consumption in July hit 12-year high According to the statistics from National Bureau of Statistics of China, the retail sales of social consumer goods reached RMB 862.9 billion yuan in July,increased by 23.3% year on year and this is the highest record since February of 1996.Statistics
<正>China and Cuba will Jointly Build up a Nickel Plant China’s Minmetals Corp. will jointly build up a nickel plant in Cuba with its Cuban partner. The new production facilities there is expected to largely increase Cuba’s present nickel production of 75,000 tons/year. According to the agreement, China will hold 49 per cent of the share with Cuba holding 51 per cent. In addi-
Voices from Textile Industry Deputies in NPC,CPPCC Annual Sessions 2010:The Dream of Textile Giant Needs Policy Support National People’s Congress and National Committee of CPPCC Annual Sessions 2010 opened on March 3rd and March 5th respectively at the Great Hall of the
Cross-Straits trade deal benefits textile cooperation Chinese mainland and Taiwan negotiators signed the long-awaited Economic Cooperation Framework Agreement (ECFA) in Chongq-ing on June 29th, a move hailed by
Six Textile Achievements Granted National Technology Award The National Technology Awards were released on Jan.11st in Beijing.Six textile achievements were acquired those awards."High Efficient Short-flow Embedded Composite Spinning Technology and Industrialization"by Shandong
<正>A 1.2 Million Ton Alumina Project Started in Henan With RMB3 billion investment, a 1.2 million tons/year alumina project started construction recently in Dengfeng City, Henan province. The first phase of the project is expected to turn out 300,000 tons alumina/year, and with RMB1 billion investment for the first phase, production will begin in July next year. This project is invested jointly by Henan’s Wuzhou Aluminium Co. Ltd. and Dengdian Electricity Group Co.. The raw materials will all come from the low grade ores left by Chalco, and in Dengfeng there are some 70 million tons of such resources. Dengdian Group has 700,000 KW of electricity capacity and it will meet the project’s requirements for water, electricity, heat and other supplies.
<正>China’s Aluminium Producers are Making Losses Due to Over Capacity According to a report from the State Development and Reform Commission. China’s aluminium production capacity is already as high as 10.3 million tons/year and the capacities staying idle is 2.6 million tons with over half of the aluminium producers making losses. Statistics shows that due to over capacity and the high alumina price, the price for electrolytic aluminium went down constantly and the aluminium producers are
<正>Jiangxi Copper Co. Receives Additional Silver Export Quota Information from China’s Jiangxi Foreign Economy and Trade Bureau shows that Jiangxi Copper Co. recently received another 50 tons of silver export quota from the Ministry of Commerce. According to Jiangxi Copper Co., it intends to sell 370 tons of silver in 2005.
<正>Jiangxi Copper Stays as China’s Top Gold and Silver Smelter Jiangxi Copper Group Co., China’s largest copper smelter, produced 12 tons of gold and 300 tons of silver in 2004, increasing by 20 per cent and 36 per cent respectively on the 2003 basis. In the recent two years, Jiangxi Copper improved the gold and silver production facilities with the gold recovery rates lifted from 76.54 per cent to 99.57 per cent, and the silver recovery rates was raised from 72.5 per cent to 98.96 per cent. The company remains as the largest gold and silver smelter in China.
<正>A China Invested Zinc Mine in Mongolia will Start Operation A zinc mine invested by China Nonferrous Metals Construction Group Corp. Ltd. in Mongolia is expected to go into operation in August this year. Based on a report, this zinc mine is the first overseas project developed by the company and also the largest one invested by a Chinese company in Mongolia. The project is built through compensation trade with the mine products for paying back the cost of construction. China has acquired 51 per cent of the shares for this project.
<正>Titanium Dioxide Plants Joined Hands for Overseas Supply Stimulated by the booming demand both in China and abroad in recent years, Guangxi titanium oxide producers have their annual production capacity exceeded 150,000 tons and their actual output is already over 120,000 tons/year. Although the province has become China’s top producer region in titanium dioxide production capacity and actual output, the development of the mines in the province has lacked behind. Presently, the province can only supply about 100,000 tons ferro-titanium concentrates, but the demand at full production capacities by the titanium dioxide producers there
2010～2011 most competitive textile enterprises unveiled China National Textile Industry Council announced recently the evaluation result of 2010～2011 most competitive textile enterprises. At the meanwhile
<正>Metal Scrap Imports Reached 6.5 Million tons in 2005 Information from a forum held recently in Guangzhou showed that in 2005, China’s imports of scrap metals reached 6.5 million tons, accounting for about one third of the world scrap metals trade and China has become the largest importer country of scrap
<正>China Faces the Shortage of Tungsten Resources Due to many years of mining and the lack of prospecting work, China is facing the shortage of tungsten resources. Tungsten ore supply is already getting tight presently. China is rich in tungsten resources with its known tungsten deposit accounting for over 60 per cent of the world, but over 80 per cent of the tungsten con-
Consumer survey: local brands are favored 75.7 percent purchasers would choose locally owned brands, if they are able to buy one in the near future, according to a latest survey done by the Horizon Key, a professional survey company. The result echoes the
<正>Policy, standard, regulation Shanghai to curb government car use to save energy Thousands of government vehicles in Shanghai will be taken off the roads for at least one day each week from the first day of November, the local government recently announced.
China Apparel Retail Sales Value+24.6%Y/Y in H1 The year-on-year growth of sales value remained stable According to the State Statistics Bureau,in the first half of 2011,the retail sales value of textile products including clothing,shoes,hats for
Textile & Garment Trading Volume Up 5.9% in Canton Fair Upon the closing of The 106th Canton Fair,the organizer reported 5.9% growth of the textile & garment trading volume.It is always regardes as a signal that the worst time for textile & garment industry has passed.Nevertheless, the break point might come at the mid of 2010 since the whole situation is still under recovery.
Textile Industry Sees Signs of an Easing Decline Under the interaction of global economic recession and easingdomestic macro environment,Chinese textile industry is also facingthe unstable drive of two markets,overseas and domestic.
Textile Exporters Report Profit Shrinking in First Four Monthse Ministry of Industry & Infor-mation Technology recently released China Industry Economic Operation Report 2011 Spring Edition, whichestimated the steady growth of con-sumer product industry in the future.From Jan. to Apr, the industrialadded value of statistics-worthy con-sumer product industry rose 14.2%;that’s 1.4 percentage points lowerfrom a year ago. Of which, the pace
Pofitable running of textile industry in the Jan.-Apr. period According to the latest figure released by the Statistics Center of China National Textile Industry Council,from January to April this year,the gross industrial output value
"蓝色"年代最新"Blue"车款潮流若以"Blue"为词根,衍生出频率最高的词组、语句会是什么?blue sky,blue sea,blueJazz,还是 blueberry?"Blue"通常寓意"蓝色"、"忧郁"、"蓝调",然而在汽车制造业,近年来却赋予了"Blue"一个新的意义:"环保"!各大厂商在争相推出"Blue"技术,如Bluetec、BlueMotion 之后,便开始了新的"环保战役"。
China Sees First Quarterly Trade Deficit in 6 Years, Textile & Clothes Trade Remains Surplus China saw a trade deficit of 1.02 billion U.S. dollars from January to March this year, the fir st quarterly trade
East China Fair Revealed Encouraging Trading Volume The just closed 20th East China Fair revealed that the trading volume reached 2.733billion USD in the fi ve days session,up21.95% from same period last year.Both the trading volume and visitor numbers implied that the foreign trade was recovering.
<正>Policy,standard,regulation Eco-friendly cars to get policy support in China Favorable policies that support the development of new energy vehicles are expected to come out this year,an insider from the China Association of Automobile Manufacturers was quoted as saying.
Major Export Markets Going Up in Frist Four Months According to Customs Data,the export of textile and clothing accumulated to 70.255 billion USD in first four months,rising 27.05% from the same period last year.
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
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.
Sgambelluri, Francesco; Diani, Marco; Altomare, Andrea; Frigerio, Elena; Drago, Lorenzo; Granucci, Francesca; Banfi, Giuseppe; Altomare, Gianfranco; Reali, Eva
Recent results have identified critical components of the T cell response involved in the initiation and amplification phases of psoriasis. However the link between T cell responses arising in the skin and the systemic inflammation associated with severe psoriasis is largely unknown. We hypothesized that specific subsets of memory T cells recirculating from the skin could play a role. We therefore dissected the circulating memory T cell compartment in patients by analyzing the TCM, TEM and Teff phenotype, the pattern of CCR4 and CCR5 chemokine receptor expression and the expression of the tissue homing molecule CD103. For each subset we calculated the correlation with the Psoriasis Area and Severity Index (PASI) and with the extent of systemic inflammation measured as serum level of the prototypic short pentraxin, C reactive protein (CRP). Validation was performed by comparison with gene expression data in psoriatic plaques. We found that circulating CD103(+)CCR4(+)CCR5(+) and CCR4(+)CCR6(-) CD8(+) Teff cells, were highly correlated with CRP levels as well as with the validated index PASI, reflecting a link between skin involvement and systemic inflammation in patients with severe psoriasis. In addition we observed a contraction of circulating CCR5(+) T cells in psoriasis patients, with a highly significant inverse correlation between CCR5(+)CD4 T cells and the PASI score. Increased expression of CCR5 and CCL5 genes in psoriatic skin lesions was consistent with an accumulation of CCR5(+) cells in psoriatic plaques indicating a role for CCR5/CCL5 axis in disease pathogenesis.
程慧玲; 刘建伟; 马万山; 迟伟玲
目的 探讨系统性红斑狼疮(SLE)患者趋化因子受体CCR4和CCR5在外周血淋巴细胞表面的表达及其意义.方法 流式细胞仪计数法对113例SLE患者和50例健康体检者外周血淋巴细胞表面CCR4和CCR5的表达情况进行检测,分析及评价SLE患者外周血淋巴细胞中CCR4+和CCR5+T淋巴细胞的百分数.结果 非狼疮性肾炎(nLN)SLE组外周血CCR4+CD4+T%明显高于健康对照组(P<0.01);狼疮性肾炎SLE组外周血CCR4+CD4+T%明显高于健康对照组(P<0.001);LN SLE组外周血CCR4+CD4+T%明显高于nLN SLE组(P<0.01);nLN SLE组外周血CCR5+CD4+T%高于健康对照组(P<0.05);LN SLE组外周血CCR5+CD4+T%明显高于健康对照组(P<0.001);LN SLE组外周血CCR5+CD4+T%明显高于nLN SLE组(P<0.01).SLE活动组血清CCR4+CD4+T%与CCR5+CD4+T%较非活动组和对照组明显升高(P<0.01);活动性狼疮性肾炎(LN)与活动性无肾损伤组及对照组比较,其差异具有显著统计学意义(P<0.01).nLN SLE组外周血CCR4+CD4+T%与CCR5+CD4+T%有相关性(r=0.619,P<0.05);LN SLE组外周血CCR4+CD4+T%与CCR5+CD4+T%有明显相关性(r=0.68,P<0.01);血清CCR4+CD4+T%水平随着SLE疾病活动水平明显升高,与总的系统性红斑狼疮疾病活动性指数(SLEDAI)评分密切相关(r=0.6382,P<0.001);与SLEDAI肾评分亦密切相关(r=0.6980,P<0.001);而CCR5+CD4+T%与疾病活动度不相关(r=0.16,P＞0.05).结论 以上结果表明CCR4和CCR5在T细胞趋化至病变部位的过程中可能发挥重要作用,CCR4+CD4+T%与CCR5+CD4+T%可能在肾损伤中起着十分重要的作用,血清CCR4+CD4+T%、CCR5+CD4+T%与SLE疾病活动密切相关,可作为SLE疾病活动,尤其是监测狼疮性肾损伤的重要指标.
Ayanna J Flegler
Full Text Available 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.
Flegler, Ayanna J; Cianci, Gianguido C; Hope, Thomas J
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.
Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R
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.
Hauser, Mark A; Kindinger, Ilona; Laufer, Julia M; Späte, Anne-Katrin; Bucher, Delia; Vanes, Sarah L; Krueger, Wolfgang A; Wittmann, Valentin; Legler, Daniel F
The homeostatic chemokines CCL19 and CCL21 and their common cognate chemokine receptor CCR7 orchestrate immune cell trafficking by eliciting distinct signaling pathways. Here, we demonstrate that human CCR7 is N-glycosylated on 2 specific residues in the N terminus and the third extracellular loop. Conceptually, CCR7 glycosylation adds steric hindrance to the receptor N terminus and extracellular loop 3, acting as a "swinging door" to regulate receptor sensitivity and cell migration. We found that freshly isolated human B cells, as well as expanded T cells, but not naïve T cells, express highly sialylated CCR7. Moreover, we identified that human dendritic cells imprint T cell migration toward CCR7 ligands by secreting enzymes that deglycosylate CCR7, thereby boosting CCR7 signaling on T cells, permitting enhanced T cell locomotion, while simultaneously decreasing receptor endocytosis. In addition, dendritic cells proteolytically convert immobilized CCL21 to a soluble form that is more potent in triggering chemotactic movement and does not desensitize the receptor. Furthermore, we demonstrate that soluble CCL21 functionally resembles neither the CCL19 nor the CCL21 phenotype but acts as a chemokine with unique features. Thus, we advance the concept of dendritic cell-dependent generation of micromilieus and lymph node conditioning by demonstrating a novel layer of CCR7 regulation through CCR7 sialylation. In summary, we demonstrate that leukocyte subsets express distinct patterns of CCR7 sialylation that contribute to receptor signaling and fine-tuning chemotactic responses.
Yoshino, Miya; Okuyama, Kazuki; Murata, Akihiko; Tomura, Michio; Hayashi, Shin-ichi
Under homeostatic conditions, skin DCs migrate to regional LNs transporting self-antigens (self-Ags). The transport of self-Ags is considered to be critical for maintaining peripheral tolerance. Although the chemokine receptor CCR7 potently induces the migration of skin DCs to regional LNs, Ccr7(-/-) (Ccr7-KO) mice do not show skin auto-immune diseases. To resolve this inconsistency, we examined Ccr7-KO epidermis- or dermis-hyperpigmented transgenic (Tg) mice, in which the transport of skin self-Ags is traceable by melanin granules (MGs). Under CCR7-deficient conditions, the transport of epidermal MGs to regional LNs was impaired at 7 weeks of age. However, epidermal MGs could be transported when they had accumulated in the dermis. Ccr7-KO-dermis-pigmented Tg mice confirmed the presence of CCR7-independent transport from the dermis. Compared with WT-dermis-pigmented Tg mice, the amount of transported melanin and number of MG-laden CD11c(+) cells were both approximately 40% of the WT levels, while the number of MG-laden CD205(+) or CD207(+) cells decreased to about 10% in skin regional LNs of Ccr7-KO-dermis-pigmented Tg mice. Cell sorting highlighted the involvement of CD11c(+) cells in the CCR7-independent transport. Here, we show that CCR7-independent transport of skin self-Ags occurs in the dermis. This system might contribute to the continuous transport of self-Ags, and maintain peripheral tolerance.
夏承来; 严鹏科; 黄汉辉
目的 研究CCR5△32及CCR5 siRNA修饰的PBMC细胞对HIV-1假病毒的拮抗作用.方法 将CCR5△32和CCR5siRNA的基因连接到腺病毒载体上,用磷酸钙法将其转入人源性PBMC,Westernblot检测CCR5△32稳定表达情况以及CCR5siRNA对CCR5的抑制情况.构建HIV-1假病毒,检测荧光素酶报告基因的活性,判断病毒的感染情况.结果 CCR5△32在PBMC细胞上获得稳定表达,CCR5siRNA抑制PBMC细胞中CCR5的表达;修饰后的PBMC细胞并不能被HIV-1假病毒感染.结论 修饰后的PBMC细胞具有较好的拮抗HIV-1假病毒感染的作用.
Mohammad Ubaidullah Bokhari
Full Text Available People are nowadays opting news search engines for searching news instead of traditional web search engines as, number of specialized news search services have been developed. So it becomes necessary to evaluate these news search systems and help users to select the best one. Lots of work has been done to measure the traditional effectiveness of web search engines, major work has been done for relevance based evaluation using precision based measures, where topical relevance is often the main selection criteria, but less work has been done to measure the time-sensitive effectiveness of the news search systems where freshness matters. In this paper we used a scheme using mathematical statistics to measure the time-sensitive effectiveness of four news search systems, i.e., how well they retrieve the fresh documents. To our knowledge there is a lack of a good measure that combines both time-independent effectiveness and the relative freshness of news items so our scheme, using top ten results for 100 news queries on four news search engines with the basic idea to pull all the relevant results from the news search systems we want to compare together into a single ranked list based on their recency and analyse the relative positions of these results, will be useful in stuffing this gap.
Santos, Erinaldo Ubirajara Damasceno dos; Lima, Géssica Dayane Cordeiro de; Oliveira, Micheline de Lucena; Heráclio, Sandra de Andrade; Silva, Hildson Dornelas Angelo da; Crovella, Sergio; Maia, Maria de Mascena Diniz; Souza, Paulo Roberto Eleutério de
Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.
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...... by a high degree of urgency. Urgency refers to the need to catch and processinputs fast. A tendency that is becoming more widespread in other industries where theproduction cycle tends to be reduced. The test is don on original data on the newspaper industrycollected by the author. The conclusions drawn...... 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...
Holst, P J; Orskov, C; Qvortrup, K;
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...
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.
Konstantis, Apostolos; Exiara, Triada
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. PMID:25709183
... collection of news for the public press or radio or television broadcasting or in the dissemination of news through the public press or by means of radio or television broadcasting; or (2) In the collection or..., press association, radio or television news broadcasting agency, or news ticker service, to any...
Bahrani, Taher; Sim, Tam Shu
The present paper focuses on the role of audio/visual mass media news in language learning. In this regard, the two important issues regarding the selection and preparation of TV news for language learning are the content of the news and the linguistic difficulty. Content is described as whether the news is specialized or universal. Universal…
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
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...... that emphasize the significance of spatiotemporal dynamics. The emphasis here is on the interrelations and mobilities of digital news audiences, based on a recognition of the productive impacts of media use while being careful to note the limitations of a paradigm shift that points solely to the possibilities...
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
Su, S B; Mukaida, N; Wang, J; Nomura, H; Matsushima, K
cDNA cloning has revealed the presence of at least three distinct human receptors for macrophage inflammatory protein-1alpha (MIP-1alpha) and RANTES: C-C chemokine receptor (CCR) 1, 4, and 5. To clarify the physiological role of CCR1, we prepared specific antibodies to CCR1 by immunizing rabbits with recombinant glutathione-S-transferase (GST) fused with its NH2-terminal portion. The resultant antibodies stained positively 293 cells transfected with CCR1 cDNA but neither parental cells nor cells transfected with CXCR1 [interleukin-8 (IL-8) receptor type A] cDNA, confirming its specificity. Immunofluorescence analysis revealed that peripheral blood lymphocytes and monocytes but not neutrophils express CCR1. Positive staining of transfectants, monocytes, and lymphocytes was inhibited by the GST protein fused with the NH2-terminal portion of CCR1, further indicating that this antibody recognized the NH2-terminal portion of CC CKR1. A majority of CD3+, CD4+, CD8+, or CD16+ peripheral blood lymphocytes but not CD19+ lymphocytes expressed CCR1. Among CD4+ peripheral blood lymphocytes, CD45RO+ cells expressed a larger number of CCR1 compared with CD45RO-. Moreover, CD34+ cells in human bone marrow as well as cord blood were uniformly stained with this antibody. Furthermore, the antibody inhibited calcium mobilization in CCR1 transfectants stimulated with human rMIP-1alpha, suggesting that its NH2-terminal portion is critically involved in ligand binding or signaling. Finally, the antibody partially inhibited monocyte chemotactic activities of human rMIP-1alpha, suggesting that CCR1 is a functional receptor for MIP-1alpha on human peripheral blood monocytes.
Pfaff, Jennifer M; Wilen, Craig B; Harrison, Jessamina E; Demarest, James F; Lee, Benhur; Doms, Robert W; Tilton, John C
We previously reported on a panel of HIV-1 clade B envelope (Env) proteins isolated from a patient treated with the CCR5 antagonist aplaviroc (APL) that were drug resistant. These Envs used the APL-bound conformation of CCR5, were cross resistant to other small-molecule CCR5 antagonists, and were isolated from the patient's pretreatment viral quasispecies as well as after therapy. We analyzed viral and host determinants of resistance and their effects on viral tropism on primary CD4(+) T cells. The V3 loop contained residues essential for viral resistance to APL, while additional mutations in gp120 and gp41 modulated the magnitude of drug resistance. However, these mutations were context dependent, being unable to confer resistance when introduced into a heterologous virus. The resistant virus displayed altered binding between gp120 and CCR5 such that the virus became critically dependent on the N' terminus of CCR5 in the presence of APL. In addition, the drug-resistant Envs studied here utilized CCR5 very efficiently: robust virus infection occurred even when very low levels of CCR5 were expressed. However, recognition of drug-bound CCR5 was less efficient, resulting in a tropism shift toward effector memory cells upon infection of primary CD4(+) T cells in the presence of APL, with relative sparing of the central memory CD4(+) T cell subset. If such a tropism shift proves to be a common feature of CCR5-antagonist-resistant viruses, then continued use of CCR5 antagonists even in the face of virologic failure could provide a relative degree of protection to the T(CM) subset of CD4(+) T cells and result in improved T cell homeostasis and immune function.
Kang, HyunJun; Minder, Petra; Park, Mi Ae; Mesquitta, Walatta-Tseyon; Torbett, Bruce E; Slukvin, Igor I
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.
Ahlenstiel, Golo; Woitas, Rainer P; Iwan, Agathe; Nattermann, Jacob; Feldmann, Georg; Rockstroh, Jürgen K; Oldenburg, Johannes; Kupfer, Bernd; Sauerbruch, Tilman; Spengler, Ulrich
In hepatitis C virus (HCV) infection antiviral T cells express the CC chemokine receptor 5 (CCR5). Their recruitment to the liver is an important step in the immune response. A 32 base pair deletion in the CCR5 gene leads to reduced expression and total loss of CCR5 in CCR5-Delta32 heterozygous and homozygous subjects, respectively. However, the role of this mutation for antiviral immunity remains unclear. Here, we analysed proliferation, IFN-gamma and IL-4 secretion (ELISpot) induced by the HCV antigens core, NS3, NS4, and NS5a in 21 anti-HCV-positive haemophiliac patients in relationship to their CCR5 genotypes (CCR5 wildtype n = 10, CCR5-Delta32 heterozygous n = 5 and CCR5-Delta32 homozygous n = 6). Furthermore, T cell migration in response to the CCR5 ligands CCL3, -4 and -5 was studied. Overall IFN-gamma responses to HCV proteins were only slightly greater in CCR5 wild-type patients than in CCR5-Delta32 carriers (0.6 versus 0.24 SFC/10(4) PBMC; p = 0.043). This difference was consistently seen with all tested HCV antigens. In contrast, neither T cell migration, nor PBMC proliferation, nor IL-4 production differed between CCR5 genotypes. Interruption of the CCR5 signalling pathway due to CCR5-Delta32 may potentially result in subtle reduction of HCV specific IFN-gamma responses in anti-HCV-positive haemophiliac patients.
陈超; 高向东; 顾觉奋
Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn
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% of the Scand......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...
Zhang, Wenbo; Wei, Rui; Chen, Su; Jiang, Jing; Li, Huiyu; Huang, Haijiao; Yang, Guang; Wang, Shuo; Wei, Hairong; Liu, Guifeng
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.
齐铁雄; 高国花; 刘世华
目的 探讨感染EB病毒的传染性单核细胞增多症(IM)患儿CCR3和CCR5的表达,以期了解Th1/Th2细胞的分化情况.方法 观察患儿外周血异型淋巴细胞比例,测定患儿的嗜异凝集抗体,用双抗体夹心酶联免疫吸附法(ELISA)测定患儿抗EBV-CA-IgM、抗EBV-CA-IgG及抗EBV-NA-IgG,筛选出符合诊断标准的IM患儿.并用流式细胞检测仪检测淋巴细胞中CCR3和CCR5的表达.结果 IM感染组异型淋巴细胞比例高于对照组(P＜0.05).IM感染组CCR3+细胞率高于对照组(P＜0.05),CCR5+细胞率低于对照组(P＜0.05).CCR3与发热持续时间、异型淋巴细胞百分数呈正相关(P＜0.05).CCR5与发热持续时间呈负相关(P＜0.05).结论 IM患儿CCR3+表达增高,CCR5+表达降低,存在以Th2细胞优势分化状态为特征的T辅助细胞分化失衡.CCR3和CCR5可以作为判断IM病情轻重的重要参考指标.%Objective To explore the expression of periphery blood leucocyte CCR3 and CCR5 and to comprehend T helper cell in the Children with Epstein-Barr virus associated infectious mononucleosis.Methods We defined the children according to the diagnosis criterion through Paul-Bunnell test inspecting the children's periphery blood unusual lymphocyte and detecting their anti-EBV-CA-IgM, anti-EBV-CA-IgG and anti-EBV-NA-IgG by ELISA and counted the ratio of CCR3 + and CCR5 + cells in lymphocytes with flow cytometry. Results The ratio of unusual lymphocyte in IM was higher than that of the healthy control group (P ＜ O. 05). The ratio of CCR3 + cells in IM group was higher than that of the healthy control group (P ＜ 0.05). The ratio of CCR5 + cells in IM group was significantly lower than that of the healthy control group. CCR3 + had direct interrelation with fever continued time and the ratio of unusual lymphocyte. There was a negative interrelation between CCR5 and fever continued time ( P ＜ 0. 05 ). Conclusions Children infectious of IM expressed higher level of CCR3 + and lower
Pablo Rodríguez; Dimitrina Jivkova Semova
En este artículo analizamos, desde la teoría del framing, la información ofre - cida por los dos canales de noticias 24 horas del grupo News Corporation, Sky News y Fox News, con relación a la crisis nuclear de Corea del Norte en el periodo 9 -23 de abril de 2013. Nos centramos en aspectos como la “foxificación”, la presencia de expertos militares en los bloques de noti - cias y los encuadres informativos. En el caso de Sky News, la información se ofrece desde el prisma de los sucesos a nivel...
Bonnie R Pedersen
Full Text Available BACKGROUND: CCR5 and CCR2 gene polymorphisms (SNPs have been associated with protection against HIV transmission in adults and with delayed progression to AIDS. The CCR5 Delta32 deletion and SNP -2459G are associated with reduced expression of the CCR5 protein. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the association between infant CCR2/CCR5 diplotype and HIV mother to child transmission (MTCT in Malawi. Blood samples from infants (n = 552 of HIV positive women who received nevirapine were genotyped using a post-PCR multiplex ligase detection reaction and haplotypes were identified based on 8 CCR2/CCR5 SNPs and the open reading frame 32 base pair deletion. Following verification of Hardy-Weinberg equilibrium, log linear regression was performed to examine the association between mutations and MTCT. Overall, protection against MTCT was weakly associated with two CCR5 SNPs, -2459G (Risk ratio [RR], 0.78; confidence interval [CI], 0.54-1.12, and the linked CCR5 -2135T (RR, 0.78; CI, 0.54-1.13. No child carried the CCR5 Delta32 SNP. Maternal Viral Load (MVL was found to be an effect measure modifier. Among mothers with low MVL, statistically significant protection against MTCT was observed for -2459G (RR, 0.50; CI, 0.27-0.91, and -2135T (RR, 0.51; CI, 0.28-0.92. Statistically significant protection was not found at high MVL. CONCLUSIONS/SIGNIFICANCE: Results from this study suggest that CCR5 SNPs -2459G and -2135T associated with reduced receptor expression protect against MTCT of HIV at low MVLs, whereas high MVLs may over-ride differences in coreceptor availability.
Barassi, C.; Soprana, E.; Pastori, C.; Longhi, R.; Buratti, E.; Lillo, F.; Marenzi, C.; Lazzarin, A.; Siccardi, A. G.; Lopalco, L.
The genital mucosa is the main site of initial human immunodeficiency virus type 1 (HIV-1) contact with its host. In spite of repeated sexual exposure, some individuals remain seronegative, and a small fraction of them produce immunoglobulin G (IgG) and IgA autoantibodies directed against CCR5, which is probably the cause of the CCR5-minus phenotype observed in the peripheral blood mononuclear cells of these subjects. These antibodies recognize the 89-to-102 extracellular loop of CCR5 in its native conformation. The aim of this study was to induce infection-preventing mucosal anti-CCR5 autoantibodies in individuals at high risk of HIV infection. Thus, we generated chimeric immunogens containing the relevant CCR5 peptide in the context of the capsid protein of Flock House virus, a presentation system in which it is possible to engineer conformationally constrained peptide in a highly immunogenic form. Administered in mice via the systemic or mucosal route, the immunogens elicited anti-CCR5 IgG and IgA (in sera and vaginal fluids). Analogous to exposed seronegative individuals, mice producing anti-CCR5 autoantibodies express significantly reduced levels of CCR5 on the surfaces of CD4+ cells from peripheral blood and vaginal washes. In vitro studies have shown that murine IgG and IgA (i) specifically bind human and mouse CD4+ lymphocytes and the CCR5-transfected U87 cell line, (ii) down-regulate CCR5 expression of CD4+ cells from both humans and untreated mice, (iii) inhibit Mip-1β chemotaxis of CD4+ CCR5+ lymphocytes, and (iv) neutralize HIV R5 strains. These data suggest that immune strategies aimed at generating anti-CCR5 antibodies at the level of the genital mucosa might be feasible and represent a strategy to induce mucosal HIV-protective immunity. PMID:15890924
Haruko Hayasaka; Daichi Kobayashi; Hiromi Yoshimura; Nakayama, Emi E.; Tatsuo Shioda; Masayuki Miyasaka
During human immunodeficiency virus (HIV) infection, enhanced migration of infected cells to lymph nodes leads to efficient propagation of HIV-1. The selective chemokine receptors, including CXCR4 and CCR7, may play a role in this process, yet the viral factors regulating chemokine-dependent T cell migration remain relatively unclear. The functional cooperation between the CXCR4 ligand chemokine CXCL12 and the CCR7 ligand chemokines CCL19 and CCL21 enhances CCR7-dependent T cell motility in v...
Schäuble, Karin; Hauser, Mark A.; Rippl, Alexandra; Bruderer, Roland; Otero, Carolina; Gröttrup, Marcus; Legler, Daniel F.
The chemokine receptor CCR7 is essential for lymphocyte and dendritic cell homing to secondary lymphoid organs. Owing to the ability to induce directional migration, CCR7 and its ligands CCL19 and CCL21 are pivotal for the regulation of the immune system. Here, we identify a novel function for receptor ubiquitylation in the regulation of the trafficking process of this G-protein-coupled seven transmembrane receptor. We discovered that CCR7 is ubiquitylated in a constitutive, ligand-independen...
Shi, Bingjie; Li, Juan; Shi, Xuanling; Jia, Wenxu; Wen, Yi; Hu, Xiongbing; Zhuang, Fengfeng; Xi, Jianzhong; Zhang, Linqi
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity, and low cytotoxicity. We report here systematic design and characterization of 28 novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity, and lower cytotoxicity compared with zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials. Sequence analysis of target cell line GHOST-CCR5-CXCR4 and human primary CD4 T cells showed that the double-strand breaks at the TALEN targeted sites resulted in truncated or nonfunctional CCR5 proteins thereby conferring protection against HIV-1 infection in vitro. None of the CCR5-TALENs had detectable levels of off-target nuclease activity against the homologous region in CCR2 although substantial level was identified for CCR5-ZFN in the primary CD4 T cells. Our results suggest that the CCR5-TALENs identified here are highly functional nucleases that produce protective genetic alterations to human CCR5. Application of these TALENs directly to the primary CD4 T cells and CD34 hematopoietic stem cells (HSCs) of infected individuals could help to create an immune system resistant to HIV-1 infection, recapitulating the success of "Berlin patient" and serving as an essential first step towards a "functional" cure of AIDS.
With the development of the whole world, news has become an essential part in our daily life. Therefore, it is very necessary to do some research on news. In view of the distinctive features of news itself and cultural differences between the West and the East, the thesis tries to discuss that to convey an accurate translation Nida ’s functional equivalence theory can be applied to compare the accuracy between the source language and the target language. A brief introduction of this theory is given at the beginning. The author puts more efforts to investigate how the theory is feasible to guide the news translation at lexical level in the next section.
Pedersen, Rasmus Tue
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.......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...
of contemporary media flows intersect with the everywhere ‘lived’ geographies of individuals, and how this changes as we move from an era of mass media consumption to digitalized media practices. It then outlines some key conceptual aspects to consider, from the spatial politics of news consumption, to questions......If we want to understand much of what makes news use meaningful for people, it is important to accentuate not only what they consume, how and when, but also where. Simply put, the places and spaces of news consumption matter, and matter significantly, for how people choose, interpret, and attend...... to the news. This chapter outlines the importance of space and place when it comes to audiences/users of journalism and the gradual recognition of this in digital journalism studies, with an eye to highlighting pertinent research trajectories. It first explores how the everyday digital geographies...
Haifa Ayub Gigawy
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
Based on the neologism in the broadcast news reporting, this paper will introduce different kinds of the most frequently used words today, including the extended meanings of the conventional words and new words created by word formation.
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
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
International audience; 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 gp1...
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.
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
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.
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.
Venuti, Assunta; Pastori, Claudia; Siracusano, Gabriel; Riva, Agostino; Sciortino, Maria Teresa; Lopalco, Lucia
Natural human Abs, recognizing an epitope within the first extramembrane loop of CCR5 (the main HIV coreceptor), induce a long-lasting internalization (48 h) of the protein, whereas all known CCR5 modulating molecules show a short-term kinetics (60-90 min). Despite extensive studies on the regulation of CCR5 signaling cascades, which are the effect of concomitant CCR5 internalization by exogenous stimuli such as Abs, downstream signaling continues to be poorly understood. In this article, we report a hitherto unrecognized mechanism of CCR5 modulation mediated by G protein-dependent ERK1 activity. We further demonstrate that ERK1 is localized mainly in the cytoplasmic compartment and that it interacts directly with the CCR5 protein, thus provoking possible CCR5 degradation with a subsequent de novo synthesis, and that re-expression of CCR5 on the cell membrane required several days. In contrast, the RANTES treatment induces a recovery of the receptor on the cell membrane in short-term kinetics without the involvement of de novo protein synthesis. The said new pathway could be relevant not only to better understand the molecular basis of all pathologic conditions in which CCR5 is involved but also to generate new tools to block viral infections, such as the use of recombinant Abs.
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
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.
Hellmann, Jason; Sansbury, Brian E; Holden, Candice R; Tang, Yunan; Wong, Blenda; Wysoczynski, Marcin; Rodriguez, Jorge; Bhatnagar, Aruni; Hill, Bradford G; Spite, Matthew
Accumulation of immune cells in adipose tissue promotes insulin resistance in obesity. Although innate and adaptive immune cells contribute to adipose inflammation, the processes that sustain these interactions are incompletely understood. Here we show that obesity promotes the accumulation of CD11c(+) adipose tissue immune cells that express C-C chemokine receptor 7 (CCR7) in mice and humans, and that CCR7 contributes to chronic inflammation and insulin resistance. We identified that CCR7(+) macrophages and dendritic cells accumulate in adipose tissue in close proximity to lymph nodes (LNs) (i.e., perinodal) and visceral adipose. Consistent with the role of CCR7 in regulating the migration of immune cells to LNs, obesity promoted the accumulation of CD11c(+) cells in LNs, which was prevented by global or hematopoietic deficiency of Ccr7 Obese Ccr7(-/-) mice had reduced accumulation of CD8(+) T cells, B cells, and macrophages in adipose tissue, which was associated with reduced inflammatory signaling. This reduction in maladaptive inflammation translated to increased insulin signaling and improved glucose tolerance in obesity. Therapeutic administration of an anti-CCR7 antibody phenocopied the effects of genetic Ccr7 deficiency in mice with established obesity. These results suggest that CCR7 plays a causal role in maintaining innate and adaptive immunity in obesity.
Cowan, Jennifer E; McCarthy, Nicholas I; Anderson, Graham
Current models of Foxp3(+) regulatory T cell (Treg) development involve CCR7-mediated migration of thymocytes into the thymus medulla to enable essential interactions with medullary epithelium. However, increased Foxp3(+) thymic Treg numbers in Ccr7(-/-) mice challenge this view, and the role of CCR7 in Treg development, emigration, and/or recirculation is unknown. Here, we have examined CCR7 and Rag2pGFP levels during Treg development and generated Rag2pGFPCcr7(-/-) mice to study its impact on the intrathymic Treg pool. We reveal surprising developmental heterogeneity in thymocytes described as Treg precursors, showing that they contain recirculating CCR6(+)CCR7(-)Rag2pGFP(-) T cells. Although CCR7 defines bona fide Rag2GFP(+) Treg precursors, it is not required for Treg production and emigration. Rather, we show that lack of CCR7 renders the thymus more receptive to Treg thymus homing. Our study reveals a role for CCR7 in limiting Treg recirculation back to the thymus and enables separation of the mechanisms controlling Treg production and thymic recirculation.
Lee, S Y; Yoo, H I; Kim, S H
Tooth movement by application of orthodontic biophysical force primarily reflects the role of soluble molecules released from the periodontal ligament (PDL). Thus far, many factors have been reported to be involved in orthodontic tooth movement (OTM), but key molecules that orchestrate responses of periodontal tissues to biophysical force are still enigmatic. In this in vivo study, in which the upper first molars in rats were moved, differential display-polymerase chain reaction revealed that CC chemokine receptor 5 (CCR5) level was differentially increased during OTM. Strong immunoreactivity for CCR5 was found in the PDL undergoing force application. Moreover, the in vitro compression or tension force application to primary cultured human PDL cells increased the expression of CCR5 and CCR5 ligands. In vitro tension force on human PDL cells did not induce RANKL, an osteoclastogenesis-inducing factor, but did induce the upregulation of IL12, an osteoclast inhibitory factor, and osteoblast differentiation factors, including Runx2, which was attenuated under tension by CCR5 gene silencing whereas augmented with CCR5 ligands. In contrast, in vitro compression force did not induce the expression of osteoprotegerin, a decoy receptor for RANKL and Runx2, but did induce the upregulation of RANKL, which was attenuated under compression by CCR5 gene silencing. These results suggest that the CCR5-CCR5 ligands axis in PDL cells may play a crucial role in the remodeling of periodontal tissues and can be a therapeutic target for achieving efficient OTM.
Sciaranghella, Gaia; Wang, Cuiwei; Hu, Haihong; Anastos, Kathryn; Merhi, Zaher; Nowicki, Marek; Stanczyk, Frank Z; Greenblatt, Ruth M; Cohen, Mardge; Golub, Elizabeth T; Watts, D Heather; Alter, Galit; Young, Mary A; Tsibris, Athe M N
Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P CCR5 expression.
Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad;
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...
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.
Elena Yuryevna Ilyinova
Full Text Available The issues stated in the article line with the current interest to pragmatic value of news releases in modern media. The news is thought to be a verbalized focal reflection of some event that was chosen by media professionals for setting the current information agenda. Having generated the opinions on the newsworthiness the authors present a set of values that may be used for measurement of relevance and clarity of an event reflection in the news content with frequency, clarity, predictability, unexpectedness, amplitude, cultural proximity, elite nations, elite people, personification, negativity among them. The novelty of the research is that the newsworthiness is checked with the focus to lexical (thematic representation of the news in a diachronic approach: the empirical base of the research was taken from the archives of UK national and local media sources (18–20th cent. and implied comparison of lexical means that reflected an event itself and some values of human interest potential in the news stories written in defined periods. The article states the trend for dynamics in the way the event is reflected in the news stories – the information core of the story is merged with detailed reporting parts, and their content is conditioned by social and moral values.
Full Text Available Efficient Market Hypothesis is the popular theory about stock prediction. With its failure much research has been carried in the area of prediction of stocks. This project is about taking non quantifiable data such as financial news articles about a company and predicting its future stock trend with news sentiment classification. Assuming that news articles have impact on stock market, this is an attempt to study relationship between news and stock trend. To show this, we created three different classification models which depict polarity of news articles being positive or negative. Observations show that RF and SVM perform well in all types of testing. Naïve Bayes gives good result but not compared to the other two. Experiments are conducted to evaluate various aspects of the proposed model and encouraging results are obtained in all of the experiments. The accuracy of the prediction model is more than 80% and in comparison with news random labelling with 50% of accuracy; the model has increased the accuracy by 30%.
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.
C-C chemokine receptor type 5 (CCR5) has been recognized as a major co-receptor in the HIV-1 entry process. Currently, many kinds of novel small molecule CCR5 antagonists for the treatment of AIDS have been identified and progressed into clinical trials. In this article, after brief introduction of the mechanism of action, current progress in drug research for various small molecule CCR5 antagonists is reviewed.%趋化因子受体5(CCR5)是HIV-1侵入宿主细胞的主要辅助受体之一.目前已发现许多小分子CCR5拮抗剂,其中一些化合物已进入临床研究和应用.本文介绍了小分子CCR5拮抗剂的作用机制,综述了近几年来各种不同结构类型的小分子CCR5拮抗剂的研究进展.
Medeiros, Gabriela A; Silvério, Jaline C; Marino, Ana Paula M P; Roffê, Ester; Vieira, Valeska; Kroll-Palhares, Karina; Carvalho, Cristiano E; Silva, Andréa Alice; Teixeira, Mauro M; Lannes-Vieira, Joseli
The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.
Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Sakata-Yanagimoto, Mamiko; Niino, Daisuke; Taniguchi, Hiroaki; Moriuchi, Yukiyoshi; Miyahara, Masaharu; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Utsunomiya, Atae; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi
Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.
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 ...
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.
Boyd, Michelle J; Zaff, Jonathan F; Phelps, Erin; Weiner, Michelle B; Lerner, Richard M
Using data from the 4-H Study of Positive Youth Development, a longitudinal study involving U.S. adolescents, multi-group structural equation modeling (SEM) was used to evaluate whether news media use is predictive of a set of civic indicators (civic duty, civic efficacy, neighborhood social connection, and civic participation) for youth in Grades 8, 9, and 10, via an indirect effect of interpersonal communication about politics with parents. The proposed model had a good fit within each grade. News media use was predictive of interpersonal communication with parents and in turn, interpersonal communication was predictive of civic duty, civic efficacy, neighborhood social connection, and civic participation. The cross-group comparison of the structural model suggests that the predictive qualities of news media use and interpersonal communication are comparable across grades. The role of media use and interpersonal communication in fostering civic development and socialization as well as implications for future research are discussed.
Garcia-Perez, Javier; Rueda, Patricia; Staropoli, Isabelle; Kellenberger, Esther; Alcami, Jose; Arenzana-Seisdedos, Fernando; Lagane, Bernard
CC chemokine receptor 5 (CCR5) is a G-protein-coupled receptor for the chemokines CCL3, -4, and -5 and a coreceptor for entry of R5-tropic strains of human immunodeficiency virus type 1 (HIV-1) into CD4(+) T-cells. We investigated the mechanisms whereby nonpeptidic, low molecular weight CCR5 ligands block HIV-1 entry and infection. Displacement binding assays and dissociation kinetics demonstrated that two of these molecules, i.e. TAK779 and maraviroc (MVC), inhibit CCL3 and the HIV-1 envelope glycoprotein gp120 binding to CCR5 by a noncompetitive and allosteric mechanism, supporting the view that they bind to regions of CCR5 distinct from the gp120- and CCL3-binding sites. We observed that TAK779 and MVC are full and weak inverse agonists for CCR5, respectively, indicating that they stabilize distinct CCR5 conformations with impaired abilities to activate G-proteins. Dissociation of [(125)I]CCL3 from CCR5 was accelerated by TAK779, to a lesser extent by MVC, and by GTP analogs, suggesting that inverse agonism contributes to allosteric inhibition of the chemokine binding to CCR5. TAK779 and MVC also promote dissociation of [(35)S]gp120 from CCR5 with an efficiency that correlates with their ability to act as inverse agonists. Displacement experiments revealed that affinities of MVC and TAK779 for the [(35)S]gp120-binding receptors are in the same range (IC(50) ∼6.4 versus 22 nm), although we found that MVC is 100-fold more potent than TAK779 for inhibiting HIV infection. This suggests that allosteric CCR5 inhibitors not only act by blocking gp120 binding but also alter distinct steps of CCR5 usage in the course of HIV infection.
Duan, Hongmei; Yang, Pingting; Fang, Fang; Ding, Shuang; Xiao, Weiguo
Rheumatoid arthritis (RA) is a systemic inflammatory disease. C-C chemokine receptor type 5 (CCR5) is found in inflamed synovium of RA patients and is necessary for formation of RA. We aimed to check whether delivery of CCR5-specific small interfering RNA (siRNA) via electroporation suppresses local inflammation in arthritis rats. Vectors encoding siRNA that target CCR5 or negative control siRNA were constructed for gene silencing and the silencing effects of suppressing CCR5 expression in synovium examined by western blot. The vector with strongest effect was delivered into the knee joint of adjuvant-induced arthritis (AIA) rats by the in vivo electroporation method 7, 10, 13, and 16 days after immunization with Complete Freund's adjuvant. During an observation of 28 days, behavior, paw swelling, arthritis and histopathologic scoring were estimated. The expression level of CCR5 in synovium was evaluated by western blot and real-time PCR. Anti-CCR5 D1 siRNA was effectively inhibited CCR5 expression in vitro. Moreover, delivery of the siRNA into inflammatory joint also suppressed the expression of CCR5 in vivo and markedly suppressed paw swelling and inflammation. Local electroporation of anti-CCR5 siRNA into the left inflamed joints could achieve the silencing of CCR5 gene and alleviate local inflammation just in the knee joint injected with siRNA other than the opposite joint. Inhibition of CCR5 expression may provide a potential for treatment of RA.
Picard, "News Coverage as the Contagion of Terrorism: Dangerous Charged Backed by Dubious Science," Political Communication and Persuasion 3 (1986): 386...September 18, 1972): 34. Picard, Robert G. "News Coverage as the Contagion of Terrorism: Dangerous Charges Backed by Dubious Science." Political Communication and
Wulfemeyer, K. Tim; McFadden, Lori L.
To date, most of the scholarly research and critical articles about ethics in journalism have dealt with newspapers and television rather than with radio. To help fill this gap, a study surveyed a segment of the radio news community to determine some of the attitudes, values, and beliefs of news directors concerning ethics in their workplace.…
Full Text Available Abstract Background Maraviroc (MVC and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug-bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists in vitro is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists in vitro including MVC, vicriviroc and AD101. Findings Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293-Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists. Conclusions Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC-bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists in vitro. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC.
Iversen, Astrid K. N.; Christiansen, Claus Bohn; Attermann, Jørn
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...
Yoshiura, Chie; Ueda, Takumi; Kofuku, Yutaka; Matsumoto, Masahiko; Okude, Junya; Kondo, Keita; Shiraishi, Yutaro; Shimada, Ichio, E-mail: email@example.com [The University of Tokyo, Graduate School of Pharmaceutical Sciences (Japan)
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.
Yoshiura, Chie; Ueda, Takumi; Kofuku, Yutaka; Matsumoto, Masahiko; Okude, Junya; Kondo, Keita; Shiraishi, Yutaro; Shimada, Ichio
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.
Schneider, M. A.; Meingassner, J. G.; Lipp, M.; Moore, H D; Rot, A.
CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice displa...
Fox, James M; Kasprowicz, Richard; Hartley, Oliver; Signoret, Nathalie
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. However, the effect of CCR5 conformations on other cell types and on the process of down-modulation remains unclear. We used mAbs, some already shown to detect distinct CCR5 conformations, to compare the behavior of CCR5 on in vitro generated human T cell blasts, monocytes and MDMs and CHO-CCR5 transfectants. All human cells express distinct antigenic forms of CCR5 not detected on CHO-CCR5 cells. The recognizable populations of CCR5 receptors exhibit different patterns of down-modulation on T lymphocytes compared with myeloid cells. On T cell blasts, CCR5 is recognized by all antibodies and undergoes rapid chemokine-mediated internalization, whereas on monocytes and MDMs, a pool of CCR5 molecules is recognized by a subset of antibodies and is not removed from the cell surface. We demonstrate that this cell surface-retained form of CCR5 responds to prolonged treatment with more-potent chemokine analogs and acts as an HIV-1 coreceptor. Our findings indicate that the regulation of CCR5 is highly specific to cell type and provide a potential explanation for the observation that native chemokines are less-effective HIV-entry inhibitors on macrophages compared with T lymphocytes.
Adlakha, Deepti; Hipp, J Aaron; Brownson, Ross C
Physical inactivity is the fourth leading risk factor for global mortality, with most of these deaths occurring in low and middle-income countries (LMICs) like India. Research from developed countries has consistently demonstrated associations between built environment features and physical activity levels of populations. The development of culturally sensitive and reliable measures of the built environment is a necessary first step for accurate analysis of environmental correlates of physical activity in LMICs. This study systematically adapted the Neighborhood Environment Walkability Scale (NEWS) for India and evaluated aspects of test-retest reliability of the adapted version among Indian adults. Cultural adaptation of the NEWS was conducted by Indian and international experts. Semi-structured interviews were conducted with local residents and key informants in the city of Chennai, India. At baseline, participants (N = 370; female = 47.2%) from Chennai completed the adapted NEWS-India surveys on perceived residential density, land use mix-diversity, land use mix-access, street connectivity, infrastructure and safety for walking and cycling, aesthetics, traffic safety, and safety from crime. NEWS-India was administered for a second time to consenting participants (N = 62; female = 53.2%) with a gap of 2-3 weeks between successive administrations. Qualitative findings demonstrated that built environment barriers and constraints to active commuting and physical activity behaviors intersected with social ecological systems. The adapted NEWS subscales had moderate to high test-retest reliability (ICC range 0.48-0.99). The NEWS-India demonstrated acceptable measurement properties among Indian adults and may be a useful tool for evaluation of built environment attributes in India. Further adaptation and evaluation in rural and suburban settings in India is essential to create a version that could be used throughout India.
Full Text Available Physical inactivity is the fourth leading risk factor for global mortality, with most of these deaths occurring in low and middle-income countries (LMICs like India. Research from developed countries has consistently demonstrated associations between built environment features and physical activity levels of populations. The development of culturally sensitive and reliable measures of the built environment is a necessary first step for accurate analysis of environmental correlates of physical activity in LMICs. This study systematically adapted the Neighborhood Environment Walkability Scale (NEWS for India and evaluated aspects of test-retest reliability of the adapted version among Indian adults. Cultural adaptation of the NEWS was conducted by Indian and international experts. Semi-structured interviews were conducted with local residents and key informants in the city of Chennai, India. At baseline, participants (N = 370; female = 47.2% from Chennai completed the adapted NEWS-India surveys on perceived residential density, land use mix-diversity, land use mix-access, street connectivity, infrastructure and safety for walking and cycling, aesthetics, traffic safety, and safety from crime. NEWS-India was administered for a second time to consenting participants (N = 62; female = 53.2% with a gap of 2–3 weeks between successive administrations. Qualitative findings demonstrated that built environment barriers and constraints to active commuting and physical activity behaviors intersected with social ecological systems. The adapted NEWS subscales had moderate to high test-retest reliability (ICC range 0.48–0.99. The NEWS-India demonstrated acceptable measurement properties among Indian adults and may be a useful tool for evaluation of built environment attributes in India. Further adaptation and evaluation in rural and suburban settings in India is essential to create a version that could be used throughout India.
Adlakha, Deepti; Hipp, J. Aaron; Brownson, Ross C.
Physical inactivity is the fourth leading risk factor for global mortality, with most of these deaths occurring in low and middle-income countries (LMICs) like India. Research from developed countries has consistently demonstrated associations between built environment features and physical activity levels of populations. The development of culturally sensitive and reliable measures of the built environment is a necessary first step for accurate analysis of environmental correlates of physical activity in LMICs. This study systematically adapted the Neighborhood Environment Walkability Scale (NEWS) for India and evaluated aspects of test-retest reliability of the adapted version among Indian adults. Cultural adaptation of the NEWS was conducted by Indian and international experts. Semi-structured interviews were conducted with local residents and key informants in the city of Chennai, India. At baseline, participants (N = 370; female = 47.2%) from Chennai completed the adapted NEWS-India surveys on perceived residential density, land use mix-diversity, land use mix-access, street connectivity, infrastructure and safety for walking and cycling, aesthetics, traffic safety, and safety from crime. NEWS-India was administered for a second time to consenting participants (N = 62; female = 53.2%) with a gap of 2–3 weeks between successive administrations. Qualitative findings demonstrated that built environment barriers and constraints to active commuting and physical activity behaviors intersected with social ecological systems. The adapted NEWS subscales had moderate to high test-retest reliability (ICC range 0.48–0.99). The NEWS-India demonstrated acceptable measurement properties among Indian adults and may be a useful tool for evaluation of built environment attributes in India. Further adaptation and evaluation in rural and suburban settings in India is essential to create a version that could be used throughout India. PMID:27049394
Berg, Christian; Spiess, Katja; von Lüttichau, Hans Rudolf;
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...
... AGENCY 40 CFR Parts 141 and 142 Announcement of Public Meeting on the Consumer Confidence Report (CCR... Internet on February 23, 2012, to obtain stakeholder input on the Consumer Confidence Report (CCR) Rule as.... Background: Consumer Confidence Reports are a key part of the public's right-to-know as established in...
An, Jun-Ling; Ishida, Yuko; Kimura, Akihiko; Tsokos, Michael; Kondo, Toshikazu
Sepsis is a systemic inflammatory disease with high mortality. In the present study, we immunohistochemically examined CCR2 and CX3CR1 expression in sepsis-induced lung injury, and discussed its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48h. Immunohistochemically, mononuclear cells recruited into the lungs expressed CCR2 and CX3CR1 in both sepsis and non-septic groups. In double-color immunofluorescence analysis, CCR2- or CX3CR1-positive cells could be identified as CD68-positive macrophages. Moreover, most of CD68-positive macrophages expressed both CCR2 and CX3CR1. Morphometrically, the average of CCR2- and CX3CR1-positive macrophages was significantly increased in sepsis group, compared with control group (sepsis vs. control: 41.6+/-1.3% vs. 8.0+/-0.4% in CCR2; 36.2+/-1.3% vs. 9.2+/-0.4% in CX3CR1). These observations implied that CCR2- or CX3CR1-positive macrophages were recruited into the lungs under several pathological conditions. In particular, their recruitment might be more evident in sepsis. Moreover, from the forensic aspects, immunohistochemical detection of CCR2 and CX3CR1 expression in the lungs can be considered as valuable diagnostic tools for the postmortem diagnosis of sepsis.
Santella, Joseph B; Gardner, Daniel S; Duncia, John V; Wu, Hong; Dhar, Murali; Cavallaro, Cullen; Tebben, Andrew J; Carter, Percy H; Barrish, Joel C; Yarde, Melissa; Briceno, Stephanie W; Cvijic, Mary Ellen; Grafstrom, R Robert; Liu, Richard; Patel, Sima R; Watson, Andrew J; Yang, Guchen; Rose, Anne V; Vickery, Rodney D; Caceres-Cortes, Janet; Caporuscio, Christian; Camac, Daniel M; Khan, Javed A; An, Yongmi; Foster, William R; Davies, Paul; Hynes, John
High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.
Xu, Guoyan G; Guo, Jia; Wu, Yuntao
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.
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.
Muntinghe, Friso L. H.; Carrero, Juan Jesus; Navis, Gerjan; Stenvinkel, Peter
Background and aims: Recently we reported on a genetically predisposed protection from C-reactive protein (CRP) related mortality in dialysis patients carrying the functional CC-chemokine receptor 5 deletion 32 allele (CCR5 Delta 32) mutation. Since CCR5 Delta 32 is associated with a less pro-inflam
Heather L Evans-Marin
Full Text Available T cells reactive to microbiota regulate the pathogenesis of inflammatory bowel disease (IBD. As T cell trafficking to intestines is regulated through interactions between highly specific chemokine-chemokine receptors, efforts have been made to develop intestine-specific immunosuppression based on blocking these key processes. CCR9, a gut-trophic chemokine receptor expressed by lymphocytes and dendritic cells, has been implicated in the regulation of IBD through mediating recruitment of T cells to inflamed sites. However, the role of CCR9 in inducing and sustaining inflammation in the context of IBD is poorly understood. In this study, we demonstrate that CCR9 deficiency in effector T cells and Tregs does not affect the development of colitis in a microbiota antigen-specific, T cell-mediated model. However, Treg cells express higher levels of CCR9 compared to those in effector T cells. Interestingly, CCR9 inhibits Treg cell development, in that CCR9-/- mice demonstrate a high level of Foxp3+ Tregs, and ligation of CCR9 by its ligand CCL25 inhibits Treg cell differentiation in vitro. Collectively, our data indicate that in addition to acting as a gut-homing molecule, CCR9 signaling shapes immune responses by inhibiting Treg cell development.
Xia, X; Liu, K; Zhang, H; Shang, Z
Metastasis is an important cause of cancer-related mortality. In this study, we investigated the role of CCR7 in the lymph node metastasis of tongue carcinoma. Immunohistochemistry and Western blot revealed the expression of CCR7 in tongue SCC tissues and cell lines. In addition, we examined the expression of CCL21, a ligand of CCR7, in normal and diseased lymph nodes using immunohistochemistry and/or real-time PCR. The CCR7 expression was significantly correlated with cervical lymph node metastasis, tumor staging, and histological grade (P = 0.015, 0.040, and 0.015, respectively). The multivariate analysis showed that regional lymph node metastasis, the expression of CCR7, and LVD were the independent poor prognostic factors. Knockdown of CCR7 gene resulted in a significant inhibition of migration and invasion of SCC4 cells in vitro without affecting the proliferation and apoptosis of tumor cells. Also, CCR7 knockdown obviously inhibited cervical lymph node metastasis in an animal tumor model. Our study indicated that CCR7 may play an important role in progression of tongue SCC and could be a promising target for tongue SCC therapy.
Martens, H. A.; Kallenberg, C. G. M.; Bijl, M.
CCR5 and its ligands play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A deletion of 32 bp in its gene leads to the production of a non-functional receptor. Although a protective effect of CCR5 Delta 32 for the development of RA has been suggested, future stud
A.W.R. van Kuijk; C.E. Vergunst; D.M. Gerlag; B. Bresnihan; J.J. Gomez-Reino; R. Regine; P.C. Verschueren; C. van der Leij; M. Maas; M.C. Kraan; P.P. Tak
Objective C-C chemokine receptor type 5 (CCR5), a chemokine receptor expressed on T cells and macrophages, and its ligands are found in inflamed synovial tissue (ST) of patients with rheumatoid arthritis (RA). The rationale for testing CCR5 blockade in patients with RA was supported by the effects o
Boyd, Michelle J.; Zaff, Jonathan F.; Phelps, Erin; Weiner, Michelle B.; Lerner, Richard M.
Using data from the 4-H Study of Positive Youth Development, a longitudinal study involving U.S. adolescents, multi-group structural equation modeling (SEM) was used to evaluate whether news media use is predictive of a set of civic indicators (civic duty, civic efficacy, neighborhood social connection, and civic participation) for youth in Grades…
肖君华; 胡芳; 徐红岩; 苏兵; 蒋跃明; 罗竞春; 张蔚翎; 谈家桢; 金力; 卢大儒
CCR5-Δ2, CCR2-641, mutants in two chemokine receptors and SDF1-3’ A, mutant in a ligand gene, can delay AIDS pathogenesis. The distribution of the three polymorphic loci was studied in 1 046 DNA samples from 26 provinces (cities) in China. No CCR5-Δ32 was observed. CCR2-64I and SDF1-3’ A had reverse distribution cline from south to north in China, with average frequency of 20.8% and 24.8% respectively. Relative hazard was evaluated. Important information to the epidemiology of AIDS and the origin and spread of these polymorphic loci in Chinese was provided.
CCR5-Δ32,CCR2-64I,mutants in two chemokine receptors and SDF1-3′A,mutant in a ligand gene,can delay AIDS pathogenesis.The distribution of the three polymorphic loci was studied in 1 046 DNA samples from 26 provinces (cities) in China.No CCR5-Δ32 was observed.CCR2-64I and SDF1-3′A had reverse distribution cline from south to north in China,with average frequency of 20.8% and 24.8% respectively.Relative hazard was evaluated.Important information to the epidemiology of AIDS and the origin and spread of these polymorphic loci in Chinese was provided.
左亚刚; 王宝玺; 刘秀荣; 赵芃; 阎倩姝
目的 探讨CCR5△32基因多态性与尖锐湿疣的关系.方法 收集60例尖锐湿疣患者和50例健康对照者的DNA标本,采用PCR方法 扩增CCR5基因片段,比较两组的基因型差别.结果 60例尖锐湿疣和50例健康对照者中均未发现突变型CCR5 △32基因型.结论 CCR5 △32基因多态性与尖锐湿疣无相关性.
Pon, R K; Cardenas, A F; Buttler, D J
An explosive growth of online news has taken place. Users are inundated with thousands of news articles, only some of which are interesting. A system to filter out uninteresting articles would aid users that need to read and analyze many articles daily, such as financial analysts and government officials. The most obvious approach for reducing the amount of information overload is to learn keywords of interest for a user (Carreira et al., 2004). Although filtering articles based on keywords removes many irrelevant articles, there are still many uninteresting articles that are highly relevant to keyword searches. A relevant article may not be interesting for various reasons, such as the article's age or if it discusses an event that the user has already read about in other articles. Although it has been shown that collaborative filtering can aid in personalized recommendation systems (Wang et al., 2006), a large number of users is needed. In a limited user environment, such as a small group of analysts monitoring news events, collaborative filtering would be ineffective. The definition of what makes an article interesting--or its 'interestingness'--varies from user to user and is continually evolving, calling for adaptable user personalization. Furthermore, due to the nature of news, most articles are uninteresting since many are similar or report events outside the scope of an individual's concerns. There has been much work in news recommendation systems, but none have yet addressed the question of what makes an article interesting.
Full Text Available News reading has changed from the traditional model of hardcopy newspapers to online news access. Thousands of news sources are available on internet each having millions of articles to choose from, leaving users tangled to find out a relevant article that matches their interests and liking. Recommender Systems can be used as a solution to this information overload problem by identifying the interest areas of a user by creating user profiles, maintaining those profiles to keep accommodating changing user interests and presenting a set of recent news articles formed as recommendations based on those user profiles. This paper presents an algorithm, which requests one time input from users (during the signup about their preference of news categories (like Sports, Entertainment etc., which they would like to subscribe and creates a personalized profile for each user. Subsequently, it requests an optional feedback on the recommended articles, to intelligently update user profiles, and recommend relevant articles to them, based on their changing interests. The paper also presents a simulation of the proposed algorithm on various use cases to depict the correctness and robustness of the algorithm. Also, it gives a brief idea about implementation details and challenges associated with the algorithm.
Reis Junior, Jose S.B.; Barroso, Antonio C.O.; Menezes, Mario O., E-mail: firstname.lastname@example.org, E-mail: email@example.com, E-mail: firstname.lastname@example.org [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)
Using a modified epidemiological model, the dissemination of news by media agents after the occurrence of large scale disasters was studied. A modified compartmented model was developed in a previous paper presented at INAC 2007. There it used to study to the Chernobyl's nuclear accident (1986) and the Concorde airplane crash (2000). Now the model has been applied to a larger and more diverse group of events - nuclear, non-nuclear and naturally caused disasters. To be comprehensive, old and recent events from various regions of the world were selected. A more robust news repository was used, and improved search techniques were developed to ensure that the scripts would not count false positive news. The same model was used but with improved non-linear embedded simulation optimization algorithms to generate the parameters of interest for our model. Individual parameters and some specific combination of them allow some interesting perceptions on how the nature of the accident / disaster gives rise to different profiles of growth and decay of the news. In our studies events involving nuclear causes generate news repercussion with more explosive / robust surge profiles and longer decaying tails than those of other natures. As a consequence of these differences, public opinion and policy makers are also much more sensitive to some issues than to others. The model, through its epidemiological parameters, shows in quantitative manner how 'nervous' the media content generators are with respect to nuclear installations and how resilient this negative feelings about nuclear is. (author)
Sibley, Chris G.; Osborne, Danny; Bulbulia, Joseph
News coverage of Islamic extremism is reigniting debates about the media’s role in promoting prejudice toward Muslims. Psychological theories of media-induced prejudice date to the 1950’s, and find support from controlled experiments. However, national-scale studies of media effects on Muslim prejudice are lacking. Orthogonal research investigating media-induced prejudice toward immigrants has failed to establish any link. Moreover, it has been found that people interpret the news in ways that confirm pre-existing attitudes, suggesting that media induced Muslim prejudice in liberal democracies is unlikely. Here, we test the association between news exposure and anti-Muslim prejudice in a diverse national sample from one of the world’s most tolerant societies, where media effects are least likely to hold (N = 16,584, New Zealand). In support of media-induced Islamophobia, results show that greater news exposure is associated with both increased anger and reduced warmth toward Muslims. Additionally, the relationship between media exposure and anti-Muslim prejudice does not reliably vary with political ideology, supporting claims that it is widespread representations of Muslims in the news, rather than partisan media biases, that drives anti-Muslim prejudice. PMID:28362823
Barr, Erika L; Ouburg, Sander; Igietseme, Joseph U; Morré, Servaas A; Okwandu, Edith; Eko, Francis O; Ifere, Godwin; Belay, Tesfaye; He, Qing; Lyn, Deborah; Nwankwo, Gift; Lillard, James W; Black, Carolyn M; Ananaba, Godwin A
T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification of the immunogenetic factors predisposing to complication development. The chemokine receptor CCR5 is crucial for T cell activation and function since its deficiency causes suppression of T cell response. We investigated the hypothesis that the clearance of genital chlamydial infection in CCR5-deficient mice could be delayed in the short term; however, a beneficial effect could include protection against inflammation-related complications such as TFI. In a translational study in humans, we investigated the effect of a functional 32 bp deletion in the CCR5 gene on the risk of developing tubal pathology in Dutch Caucasian women with immunologic evidence [i.e., immunoglobulin G (IgG) responses] of chlamydial infection. When genitally-infected wild-type (WT) and CCR5 knockout (CCR5KO) mice were evaluated for microbiologic shedding of chlamydiae, there was a greater intensity of infection and delayed resolution in the knockout mice. However, compared to WT mice, the fertility of infected CCR5KO mice (measured by pregnancy rate) was only mildly affected in the short term and unaffected in the long term (70% vs 30% reduction in the short term, and 50 vs 0% in the long term, respectively). Immunobiologic analysis revealed that the diminished capacity of CCR5KO to control acute chlamydial infection correlated with the relatively low chemokine [interferon-inducible protein 10 (IP-10) and regulated upon activation normal cell expressed and secreted (RANTES)] and cytokine (mainly interferon-gamma and tumor necrosis
Gupta, A; Padh, Harish
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.
冯潇; 程胖; 赵洁; 肖岚; 李臻
Objective:To observe the expression and the cellular localization of regulated upon activation normal T-cell expressed and secreted (RANTES) as well as its receptors CCR1 and CCR5 in the rat epididymis.Methods:Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of RANTES and its receptors mRNA in rat epididymis.The presence of RANTES and its receptors protein was assayed by Western blotting.Paraffin-embedded sections were prepared from rat epididymis,and immunohistochemical staining was carried out to detect cellular location of RANTES and its receptors.Colocalization of RANTES,CCR1,and CCR5 in rat epididymis was detected by immunofluorescence.Results:RT-PCR analysis showed the specific expression of RANTES and its receptors in the segments of adult rat epididymis.The distinctive single band of RANTES protein and its receptors protein was identified in the segments of rat epididymis with Western blotting.The positive staining of RANTES and its receptors were mainly observed in the basal cells of the epididymal epithelium.The immunofluorescence of RANTES coincided with CCR1 and CCR5 in the basal cells of epididymis.Conclusion:The expressions of RANTES and its receptors CCR1 and CCR5 were found restricted in the basal cells of the rat epididymis.These results revealed that RANTES may play a role in the physiological function of the basal cells of rat epididymis through autocrine or/and paracrine way.%目的:观察受激活调节正常T细胞表达和分泌因子(RANTES)与其受体CCR1、CCR5在大鼠附睾中的表达和定位.方法:采用免疫组织化学法检测成年大鼠附睾上皮RANTES及其受体的细胞定位,免疫荧光双标染色分别显示RANTES与CCR1、CCR5的细胞共定位情况.RT-PCR检测RANTES及其受体mRNA表达水平,免疫印迹检测RANTES及其受体的蛋白量.结果:RANTES与其受体CCR1、CCR5在大鼠附睾各段呈特异性表达.免疫印迹在大鼠附睾各段检测到RANTES及其受体CCR
Cowan, Jennifer E; McCarthy, Nicholas I; Parnell, Sonia M; White, Andrea J; Bacon, Andrea; Serge, Arnauld; Irla, Magali; Lane, Peter J L; Jenkinson, Eric J; Jenkinson, William E; Anderson, Graham
αβT cell development depends upon serial migration of thymocyte precursors through cortical and medullary microenvironments, enabling specialized stromal cells to provide important signals at specific stages of their development. Although conventional αβT cells are subject to clonal deletion in the medulla, entry into the thymus medulla also fosters αβT cell differentiation. For example, during postnatal periods, the medulla is involved in the intrathymic generation of multiple αβT cell lineages, notably the induction of Foxp3(+) regulatory T cell development and the completion of invariant NKT cell development. Although migration of conventional αβT cells to the medulla is mediated by the chemokine receptor CCR7, how other T cell subsets gain access to medullary areas during their normal development is not clear. In this study, we show that combining a panel of thymocyte maturation markers with cell surface analysis of CCR7 and CCR4 identifies distinct stages in the development of multiple αβT cell lineages in the thymus. Although Aire regulates expression of the CCR4 ligands CCL17 and CCL22, we show that CCR4 is dispensable for thymocyte migration and development in the adult thymus, demonstrating defective T cell development in Aire(-/-) mice is not because of a loss of CCR4-mediated migration. Moreover, we reveal that CCR7 controls the development of invariant NKT cells by enabling their access to IL-15 trans-presentation in the thymic medulla and influences the balance of early and late intrathymic stages of Foxp3(+) regulatory T cell development. Collectively, our data identify novel roles for CCR7 during intrathymic T cell development, highlighting its importance in enabling multiple αβT cell lineages to access the thymic medulla.
Wang, Lei; Zhang, Yong-zhen; Xu, Wen-teng; Jia, Xiao-dong; Chen, Song-lin
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.
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
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.
Full Text Available Background and Objective It has became a hotspot research about the target metastasis of malignant tumor in recent years. It has been proven that metastasis of malignant tumor is a nonrandom but highly-organized and selective process. The aim of this study is by analysing the expression of CC Chemokine Receptor 7 (CCR7 in pulmonary tumor tissue and metastasized lymph nodes in NSCLC, to explore the relationship between the expression of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and explore the significance. Methods SABC immunohitochemcal staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of Squamous cell Carcinoma, 12 cases of Adenosquamous Carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections use 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field (×400 of microscope by double blind method. Results 1. The expression of CCR7 in pulmonary tumor tissue was remarkably higher than normal lung tissue (P<0.005; 2. The expression of CCR7 between pulmonary tumor tissue and metastasized lymph nodes had no significant differences (P=0.177; 3. The expression of CCR7 had correlation with lymph nodes metastasis, The expression level in lymph nodes metastasis group was significantly higher than that in no lymph nodes metastasis group (P=0.016; 4. Along with the increment that clinical stage, the CCR7 expression had increases the high trend (P=0.003. Conclusion CCR7 is over-expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.
Employees of CERN can now sign up for a free account at Swisster.ch, an English language website devoted to Swiss news and current affairs. « prev next » The website, which is aimed at English speakers in Switzerland, normally requires an annual subscription of 300 CHF, but has teamed up with sponsors to offer a free subscription for CERN employees. The service provides a daily newsletter containing the main news and other information sent to subscribers every working day. The Swisster website also offers a variety of services such as health, education and food forums called "corners", as well as weather & snow forecasts, blogs and even a TV guide for Anglophones. The editorial team of English-speaking journalists is based in Lausanne, Geneva, Zurich and Neuchatel and covers news for expatriates and English speakers living and working in Switzerland. Swisster.ch also has a Saturday morning radio show from 08:30 to 09:30, on Radio Cit�...
Wei, Dong; Cimini, Giulio; Wu, Pei; Liu, Weiping; Zhang, Yi-Cheng
Recommendation systems represent an important tool for news distribution on the Internet. In this work we modify a recently proposed social recommendation model in order to deal with no explicit ratings of users on news. The model consists of a network of users which continually adapts in order to achieve an efficient news traffic. To optimize network's topology we propose different stochastic algorithms that are scalable with respect to the network's size. Agent-based simulations reveal the features and the performance of these algorithms. To overcome the resultant drawbacks of each method we introduce two improved algorithms and show that they can optimize network's topology almost as fast and effectively as other not-scalable methods that make use of much more information.
Morley, Sharon Celeste; Wang, Chen; Lo, Wan-Lin; Lio, Chan-Wang J.; Zinselmeyer, Bernd H.; Miller, Mark J.; Brown, Eric J.; Paul M Allen
Chemokines promote lymphocyte motility by triggering F-actin rearrangements and inducing cellular polarization. Chemokines can also enhance cell-cell adhesion and co-stimulate T cells. Here we establish a requirement for the actin-bundling protein L-plastin (LPL) in CCR7- and S1P1-mediated T cell chemotaxis using LPL−/− mice. Disrupted motility of mature LPL−/− thymocytes manifested in vivo as diminished thymic egress. Two-photon microscopy of LPL−/− lymphocytes revealed reduced velocity and ...
... gov/news/fullstory_161477.html Mixed News on Drug Abuse Among Lesbian, Gay Americans This group is more ... said Kana Enomoto, deputy principal administrator at the Substance Abuse and Mental Health Services Administration (SAMHSA). She spoke ...
Shin, J. K.
As a continuous opinion dynamics model, the information accumulation system (IAS) includes three basic mechanisms of the news, the inheritance and the diffusion as contributing to the information accumulation process of a system. A system is composed of agents who diffuse information through internal interaction, while each of them has incomplete memory or inheritance rate. The news comes from external sources of information, such as mass media. Previously the model IAS was studied only for the small news problems. In this study, a tipping news problem is considered. A key question of the problem is: what is the minimum strength of advertisement that can tip the minority opinion to a majority one? Dynamics of the IAS is briefly revisited with a special interest on nonlinear behavior of the model. In particular, it is shown that a discrete map of the IAS for a single color problem can be transformed into a logistic map, from which the dynamics of the IAS can be better understood. To show the applicability of the IAS model, the result is applied to explain the concept of the critical population size, which claims that there is a minimum population size for a social knowledge system to be continuously inherited without being lost. And critical size of the tipping news is found analytically in terms of IAS parameters. Some of the key results from the present study are compared in detail with the results from the Brownian particle model, which is believed to be the most similar model to the IAS. The concept of tipping news is used to show that a traditional society can tip at an exceptionally low inter-community exposure. Finally, the result was applied to the language competition problem.
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.
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.
周长鑫; 章阳; 孟凡云; 李文磊; 关众; 范海燕
mRNA was significantly higher in breast cancer tissues than in paracarcinoma tissues(P ＜ 0.01)and breast fibroadenoma tissues (P ＜ 0.05).The difference of relative expression quantity of CCR5 mRNA had statistical significance between breast cancer tissues in stage Ⅱ and Ⅲ(P ＜ 0.05 ),but not between breast fibroadenoma tissues and paracarcinoma tissues(P ＞0.05).2.The relative expression quantity of CCR5 mRNA was significantly higher in metastatic axillary nodes than in nonmetastatic nodes (P ＜ 0.05 ).3.Polymorphism CCR5-△32 wasn't found in any specimen.4.The relative expression of CCR5 mRNA had connection with breast oncogene C-erbB-2 and whether there was axillary lymph node metastasis,but no connection with other immunological and biochemical indicators.Conclusions CCR5 mRNA is significantly higher expressed in breast cancer and metastatic axillary nodes.The interaction between CCR5 and its ligands promotes the progress of breast cancer and axillary lymph node metastasis.CCR5 can be taken as a molecular indicator to predict axillary lymph node metastasis in breast cancer and provides new targert for clinical therapy.
Critical discourse analysis studies the relations between discourse, power, dominance, etc. and the position of the analyst. News report, which is a sociopolitical and official discourse, is often greatly affected by power or dominant ideologies and it affects people’s ideologies and attitudes. The comparative study of two pieces of news report on the same event respectively from China Daily and Times New York shows that ideology and power relationship are hidden in the public discourses and serve their purpose of forming people’s ideology.
the attacks at the Charlie Hebdo office in Paris in January 2015. This article analyses how the Danish television channel DR1 framed the attacks in the newscast from the first shot at Krudttønden and for the following week. Furthermore, the analysis will discuss how the framing of the shooting as a “terror...... attack” transformed the news coverage into a “news media” media event, abandoning the journalistic norm of critical approach while the media instead became the scene of national mourning...
Lyon, H O; Kiernan, J A
of the International Standards Organization (ISO/TC 212) and its working groups, WG 1, WG 2 and WG 3. In this issue of News from the BSC, H.O. Lyon provides information from the annual meeting of ISO/TC 212 that took place June 2-4, 2008 in Vancouver, British Columbia, Canada. In addition, under the heading......In the three earlier editions of News from the Biological Stain Commission (BSC), under the heading of "Regulatory affairs," the BSC's International Affairs Committee reported on the work of Technical Committee 212, Clinical Laboratory Testing and in Vitro Diagnostic Test Systems...
Kiernan, J.A.; Lyon, Hans Oluf
of the International Standards Organization (ISO/TC 212) and its working groups, WG 1, WG 2 and WG 3. In this issue of News from the BSC, H.O. Lyon provides information from the annual meeting of ISO/TC 212 that took place June 2-4, 2008 in Vancouver, British Columbia, Canada. In addition, under the heading......In the three earlier editions of News from the Biological Stain Commission (BSC), under the heading of "Regulatory affairs," the BSC's International Affairs Committee reported on the work of Technical Committee 212, Clinical Laboratory Testing and in Vitro Diagnostic Test Systems...
@@ Note:Hosted by China Rare Earth Information Center and National RE Information Net and sponsored by Chinese RE Society Information Specialty Committee,China RE Society Technology εt Economy Specialty Committee,Northern RE Industry Productivity Promotion Center,and principal medias in China RE industry such as publications "China RE Information" and "Chinese Rare Earths" and China RE Website,2006 Top 10 China Rare Earth Scientific News,which were selected from 100 pieces of candidate rare earth scientific news nationwide,were announced recently.
Nielsen, Kristian Hvidtfelt; Kjærgaard, Rikke Schmidt
Climate change has become one of the most favored topics in mass media, political discourses, and scientific discussions during the past decade. By the end of 2007 the scientific journals Science and Nature both demonstrated the urgency of climate change by emphasizing the importance and necessity...... of appreciating climate change, its severe consequences, and its anthropogenic causes. During that year the two journals’ online news services Nature News and ScienceNOW framed climate change to fit particular agendas resulting in markedly different narratives. This article demonstrates that Nature News reported...
The paper will present and discuss a framework for grasping some of the democratic consequences of biased TV news programs. In line with Jürgen Habermas, one can ask what consequences it has for a democratic public sphere that the national TV news landscape is biased in term of source diversity...... (gender and ethnicity). With Peter Dahlgren’s analysis of television as a space for civic identity and agency, the paper engages in a discussion of contributions and limitations of TV news framed by some of the dimensions of civic cultures (knowledge, values, trust, practices and identities)....
A good headline can not only attract readers' attention and trigger their desire to read, but also help them grasp the main points. Thus, news headlines act as guides for readers to choose the information they need. Headlines play a peculiar and essential role in news reporting. In order to understand the headline well, it's better for us to know something about the features and translations of English news headlines. In this paper, the strategies of translation of English news headlines are introduced.
Kobbernagel, Christian; Schrøder, Kim Christian
repertoires from the ensemble of old and new media available. This article presents an innovative mixed-method approach with considerable explanatory power to the exploration of patterns of news media consumption. This approach tailors Q-methodology in the direction of a qualitative study of news consumption...... of six audience news repertoires in Denmark, also preserves the qualitative thickness of the participants’ verbal accounts of the communicative figurations of their day-in-the-life with the news media...
Lei Li; Ding-Ding Wang; Shun-Zhi Zhu; Tao Li
Online news articles,as a new format of press releases,have sprung up on the Internet.With its convenience and recency,more and more people prefer to read news online instead of reading the paper-format press releases.However,a gigantic amount of news events might be released at a rate of hundreds,even thousands per hour.A challenging problem is how to efficiently select specific news articles from a large corpus of newly-published press releases to recommend to individual readers,where the selected news items should match the reader's reading preference as much as possible.This issue refers to personalized news recommendation.Recently,personalized news recommendation has become a promising research direction as the Internet provides fast access to real-time information from multiple sources around the world.Existing personalized news recommendation systems strive to adapt their services to individual users by virtue of both user and news content information.A variety of techniques have been proposed to tackle personalized news recommendation,including content-based,collaborative filtering systems and hybrid versions of these two.In this paper,we provide a comprehensive investigation of existing personalized news recommenders.We discuss several essential issues underlying the problem of personalized news recommendation,and explore possible solutions for performance improvement.Further,we provide an empirical study on a collection of news articles obtained from various news websites,and evaluate the effect of different factors for personalized news recommendation.We hope our discussion and exploration would provide insights for researchers who are interested in personalized news recommendation.
Full Text Available The 32-bp deletion in the HIV-1 co-receptor CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals for the deleted allele and partial protection against HIV-1 during disease progression in heterozygotes. Natural ligands for CCR5, MIP-1alpha, MIP-1ß and RANTES, have been shown to inhibit HIV replication in CD4+ T cells. In the present study, we examined the CCR5 genotype by PCR and the plasma levels of RANTES and MIP-1alpha by ELISA among blood donors (N = 26 and among HIV-1-infected individuals (N = 129. The control group consisted of healthy adult volunteers and HIV-1-infected subjects were an asymptomatic and heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. The frequency of the CCR5 mutant allele (delta32ccr5 in this population was 0.032; however, no delta32ccr5 homozygote was detected. These results could be related to the intense ethnic admixture of the Brazilian population. There was no correlation between circulating ß-chemokines (MIP-1alpha, RANTES and viral load in HIV-infected individuals. RANTES concentrations in plasma samples from HIV+ patients carrying the homozygous CCR5 allele (CCR5/CCR5 (28.23 ng/ml were higher than in the control samples (16.07 ng/ml; P<0.05; however, this HIV+ patient group (mean 26.23 pg/ml had significantly lower concentrations of MIP-1alpha than those observed in control samples (mean 31.20 pg/ml; P<0.05. Both HIV-1-infected and uninfected individuals heterozygous for the delta32ccr5 allele had significantly lower concentrations of circulating RANTES (mean 16.07 and 6.11 ng/ml, respectively than CCR5/CCR5 individuals (mean 28.23 and 16.07 ng/ml, respectively; P<0.05. These findings suggest that the CCR5 allele and ß-chemokine production may affect the immunopathogenesis of HIV-1.
Human immunodeficiency virus type 1 (HIV-1) infection of individuals carrying the two alleles of the CCR5Δ32 mutation (CCR5−/−) has rarely been reported, but how the virus overcomes the CCR5Δ32 protective effect in these cases has not been delineated. We have investigated this in 6 infected (HIV+) and 25 HIV− CCR5−/− individuals. CD4+ T lymphocytes isolated from HIV− CCR5−/− peripheral blood mononuclear cells (PBMCs) showed lower levels of CXCR4 expression that correlated with lower X4 Env-me...
朱长斌; 蒋子恺; 程枫; 钱关祥
CCR5, as the member of CC receptor family, with its ligands being CCL3 (MIP-1α), CCL4 (MIP-1β) and CCL5 (RANTES), is categorized as 7 trans-membrane domain G-protein coupled receptor. CCR5 is expressed in monocytes/macrophages as well as lymphocytes inducing chemotaxis and recruitment in inflammatory response and is an important co-receptor of human immunodeficiency virus ( HIV) -1 virus, leading to the multifunction of CCR5 in progression of various kind of immunological diseases and invasion of HIV-1. Moreover, the expression of CCR5 on the surface of tumor cells and stromal cells contributes to mediating multiple biological behaviors of cancers such as proliferation and invasion. Advanced technologies also lead to the revealing of structure, function, signal transduction and roles of CCRS in the progression of related diseases.%CCR5为趋化因子CC受体家族成员,属7次跨膜G蛋白耦联受体,配体为CCL3 (MIP-1α)、CCL4( MIP-1β)、CCL5( RANTES).CCR5主要表达于单核/巨噬细胞和淋巴细胞,与其配体介导CCR5+免疫细胞的趋化、募集过程.因此,多种免疫性疾病的发生和发展过程均有CCR5参与.CCR5是人类免疫缺陷病毒Ⅰ型(HIV-1)入侵时的重要辅助受体,而在肿瘤细胞和各类肿瘤相关间质细胞的表面也可见其表达,并介导肿瘤增殖、浸润等多种生物学过程.随着相关研究技术的发展,进一步加深了对CCR5的结构、功能、信号通路及其在相关疾病中的作用的认识.
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
News, by no means a neutral vehicle, is in reality ideologically driven and controlled by news values to which the use of news sources is of great help. Geis once argued that the single most important power of the press is its capacity to say what the important issues are at any particular time and to determine whose voices will be heard on any given issue (Geis, 1987:10). News sources may tell readers something, but it may also mislead readers since people cannot think about and make sense out of news events without imposing a bias on the news. It is, therefore, worth our attention and effort to understand how news source works, how it affects readers' perceptions of news events, how it is produced, how it is shaped by values and ideology.
R. van der Wurff
Internet is generally expected to have one of two effects on traditional news media: It displaces them, or it forces them into distinct market niches. A shared assumption underlying both expectations is that news media displacement, or substitution, is a function of the degree to which news media ar
Gebremeskel, G.G.; Vries, A.P. de
We investigate the role of geographic proximity in news consumption. Using a month-long log of user interactions with news items of ten information portals, we study the relationship between users' geographic locations and the geographic foci of information portals and local news categories. We find
... 7 Agriculture 6 2010-01-01 2010-01-01 false Photographs for news or advertising. 500.9 Section 500... for news or advertising. Photographs for news purposes may be taken at the USNA without prior permission. Photographs for advertising and other commercial purposes may be taken, but only with the...
Baumgartner, S.E.; Wirth, W.
The present study investigates the role of affective priming during the processing of news articles. It is assumed that the valence of the affective response to a news article will influence the processing of subsequent news articles. More specifically, it is hypothesized that participants who read
This introduction to the nonbibliographic databases offered by the Dow Jones News/Retrieval Service describes file content and search strategies in four groups: Dow Jones Business and Economic News; Dow Jones Quotes (market prices for stocks and other securities); Financial and Investment Services; General News and Information Services. Examples…
Minard, A.-L.; Speranza, M; Urizar, R.; Altuna, B.; Erp, van M.G.J.; Schoen, A.M.; Son, van C.M.
In this paper, we present the NewsReader MEANTIME corpus, a semantically annotated corpus of Wikinews articles. The corpus consists of 480 news articles, i.e. 120 English news articles and their translations in Spanish, Italian, and Dutch. MEANTIME contains annotations at different levels. The docum
Political News always reports the facts happening in the country's political life, which mainly including the guidelines, this paper aims to analyze the application of Vague Language in political news in magazine in details. In this way, to help the readers understand and appreciate the political news better.
In recent years, many world top level sports events take place in China. The exchange in sports field between China and international society adds more significance to the E-C translation of sports news. This paper analyses the lexical features of sports news and then explains some difficulties in the translation of the words of sports news.
With the metaphors in News English as data,this dissertation aims at making a breakthrough in news English translation.Based on the CIT which gives comprehensive and insightful explanation to the metaphors in news English,the author proposes two strategies applied in the metaphor translationin this area.
With the metaphors in News English as data, this dissertation aims at making a breakthrough in news English translation. Based on the CIT which gives comprehensive and insightful explanation to the metaphors in news English, the author proposes two strategies applied in the metaphor translation in this area.
Gaudino, James L.
To determine how to articulate a concrete definition of the substance of the journalist's occupation, this paper offers a propositional framework of news value based on Kurt Lewin's gatekeeper model. First, the paper follows the established suggestion that news decisions are best studied from a gatekeeping perspective or that "news is…
... media attempts to influence any Agency employee on a substantial interest matter. ... 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...
<正>Interception can shake Murdoch’s the News Corporation;can also make the president of a country quit the political scene;even can trigger a coup.There’s no exaggeration. Only knowing yourself as well as the enemy,then you can fight a hundred battles with no danger of defeat. But how can one know the enemy? Interception is the most powerful tool. It is doomed to have connection with political scene ever since its birth.
CD8 T Cells Enter the Splenic T Cell Zones Independently of CCR7, but the Subsequent Expansion and Trafficking Patterns of Effector T Cells after Infection Are Dysregulated in the Absence of CCR7 Migratory Cues.
Sharma, Naveen; Benechet, Alexandre P; Lefrançois, Leo; Khanna, Kamal M
CCR7 is an important chemokine receptor that regulates T cell trafficking and compartmentalization within secondary lymphoid organs. However, the T cell-intrinsic role of CCR7 during infection in the spleen is not well understood. This study was designed to understand how CCR7-dependent localization and migration of CD8(+) T cells in different compartments of the spleen affected the primary and recall responses after infection. To this end, we used adoptive transfer of naive Ag-specific CD8 T cells (OT-I) that either lacked CCR7 or constitutively expressed CCR7 (CD2-CCR7) in mice that were subsequently infected i.v. with Listeria monocytogenes. We show that naive CCR7(-/-)CD8(+) T cells failed to enter the T cell zone, whereas CD2-CCR7 OT-I cells were exclusively confined to the T cell zones of the spleen. Surprisingly, however, CCR7(-/-) OT-I cells entered the T cell zones after infection, but the entry and egress migratory pattern of these cells was dysregulated and very distinct compared with wild-type OT-I cells. Moreover, CCR7-deficient OT-I cells failed to expand robustly when compared with wild-type OT-I cells and were preferentially skewed toward a short-lived effector cell differentiation pattern. Interestingly, CCR7(-/-), CD2-CCR7, and wild-type OT-I memory cells responded equally well to rechallenge infection. These results highlight a novel role of CCR7 in regulating effector CD8 T cell migration in the spleen and demonstrate differential requirement of CCR7 for primary and secondary CD8 T cell responses to infection.
Mathieu Paul Rodero
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.
Full Text Available BACKGROUND: Dimerization has emerged as an important feature of chemokine G-protein-coupled receptors. CXCR4 and CCR5 regulate leukocyte chemotaxis and also serve as a co-receptor for HIV entry. Both receptors are recruited to the immunological synapse during T-cell activation. However, it is not clear whether they form heterodimers and whether ligand binding modulates the dimer formation. METHODOLOGY/PRINCIPAL FINDINGS: Using a sensitive Fluorescence Resonance Energy Transfer (FRET imaging method, we investigated the formation of CCR5 and CXCR4 heterodimers on the plasma membrane of live cells. We found that CCR5 and CXCR4 exist as constitutive heterodimers and ligands of CCR5 and CXCR4 promote different conformational changes within these preexisting heterodimers. Ligands of CCR5, in contrast to a ligand of CXCR4, induced a clear increase in FRET efficiency, indicating that selective ligands promote and stabilize a distinct conformation of the heterodimers. We also found that mutations at C-terminus of CCR5 reduced its ability to form heterodimers with CXCR4. In addition, ligands induce different conformational transitions of heterodimers of CXCR4 and CCR5 or CCR5(STA and CCR5(Delta4. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest a model in which CXCR4 and CCR5 spontaneously form heterodimers and ligand-binding to CXCR4 or CCR5 causes different conformational changes affecting heterodimerization, indicating the complexity of regulation of dimerization/function of these chemokine receptors by ligand binding.
Lee, Chul-Joo; Long, Marilee; Slater, Michael D; Song, Wen
The authors compared local TV news with national TV news in terms of cancer coverage using a nationally representative sample of local nightly TV and national network TV (i.e., ABC, CBS, NBC, and CNN) cancer news stories that aired during 2002 and 2003. Compared with national TV news, local TV cancer stories were (a) much shorter in length, (b) less likely to report on cancer prevention (i.e., preventive behaviors and screening tests), and (c) less likely to reference national organizations (i.e., National Cancer Institute, American Cancer Society, National Institutes of Health, Centers for Disease Control and Prevention, Food and Drug Administration) that have made clear recommendations about ways to prevent cancer. The implications of these findings for health communication research and cancer education were discussed.
Arvind B Chavhan
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.
Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau
Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis. PMID:26691857
Tamamis, Phanourios; Floudas, Christodoulos A
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.
Qi, Chunxia; Jia, Xiaopeng; Lu, Lingling; Ma, Ping; Wei, Min
C-C chemokine receptor 5 (CCR5) is a receptor for chemokines and a co-receptor for HIV-1 entry into the target CD4+ cells. CCR5 delta 32 deletion is a loss-of-function mutation, resistant to HIV-1 infection. We tried to induce the CCR5 delta 32 mutation harnessing the genome editing technique, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR and CRISPR associated protein 9, Cas9) in the commonly used cell line human embryonic kidney HEK 293T cells. Surprisingly, we found that HEK293T cells are heterozygous for CCR5 delta 32 mutation, in contrast to the wild type CCR5 cells, human acute T cell leukemia cell line Jurkat and human breast adenocarcinoma cell line MDA-MB-231 cells. This finding indicates that at least one human cell line is heterozygous for the CCR5 delta 32 mutation. We also found that in PCR amplification, wild type CCR5 DNA and mutant delta 32 DNA can form mismatched heteroduplex and move slowly in gel electrophoresis.
Full Text Available C-C chemokine receptor 5 (CCR5 is a receptor for chemokines and a co-receptor for HIV-1 entry into the target CD4+ cells. CCR5 delta 32 deletion is a loss-of-function mutation, resistant to HIV-1 infection. We tried to induce the CCR5 delta 32 mutation harnessing the genome editing technique, CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR and CRISPR associated protein 9, Cas9 in the commonly used cell line human embryonic kidney HEK 293T cells. Surprisingly, we found that HEK293T cells are heterozygous for CCR5 delta 32 mutation, in contrast to the wild type CCR5 cells, human acute T cell leukemia cell line Jurkat and human breast adenocarcinoma cell line MDA-MB-231 cells. This finding indicates that at least one human cell line is heterozygous for the CCR5 delta 32 mutation. We also found that in PCR amplification, wild type CCR5 DNA and mutant delta 32 DNA can form mismatched heteroduplex and move slowly in gel electrophoresis.
Boyle, S T; Ingman, W V; Poltavets, V; Faulkner, J W; Whitfield, R J; McColl, S R; Kochetkova, M
The chemokine receptor CCR7 is widely implicated in breast cancer pathobiology. Although recent reports correlated high CCR7 levels with more advanced tumor grade and poor prognosis, limited in vivo data are available regarding its specific function in mammary gland neoplasia and the underlying mechanisms involved. To address these questions we generated a bigenic mouse model of breast cancer combined with CCR7 deletion, which revealed that CCR7 ablation results in a considerable delay in tumor onset as well as significantly reduced tumor burden. Importantly, CCR7 was found to exert its function by regulating mammary cancer stem-like cells in both murine and human tumors. In vivo experiments showed that loss of CCR7 activity either through deletion or pharmacological antagonism significantly decreased functional pools of stem-like cells in mouse primary mammary tumors, providing a mechanistic explanation for the tumor-promoting role of this chemokine receptor. These data characterize the oncogenic properties of CCR7 in mammary epithelial neoplasia and point to a new route for therapeutic intervention to target evasive cancer stem cells.
Full Text Available Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+ and mature dendritic (MHCII+CD11c+ cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.
Affò, Silvia; Rodrigo-Torres, Daniel; Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau
Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.
Zhao, Lanfu; Wang, Yuan; Xue, Yafei; Lv, Wenhai; Zhang, Yufu; He, Shiming
Glioblastoma (GBM) is the most prevalent malignant primary brain tumor in adults and exhibits a spectrum of aberrantly aggressive phenotype. Tumor cell proliferation and invasion are critically regulated by chemokines and their receptors. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. Nonetheless, the roles of the CCR5 in GBM still remain unclear. The present study provides the evidence that the chemokine receptor CCR5 is highly expressed and associated with poor prognosis in human GBM. Mechanistically, CCL5-CCR5 mediates activation of Akt, and subsequently induces proliferation and invasive responses in U87 and U251 cells. Moreover, down-regulation of CCR5 significantly inhibited the growth of glioma in U87 tumor xenograft mouse model. Finally, high CCR5 expression in GBM is correlated with increased p-Akt expression in patient samples. Together, these findings suggest that the CCR5 is a critical molecular event associated with gliomagenesis.
Andrews, Glen; Jones, Carolyn; Wreggett, Keith A
A novel mechanism for antagonism of the human chemokine receptors CCR4 and CCR5 has been discovered with a series of small-molecule compounds that seems to interact with an allosteric, intracellular site on the receptor. The existence of this site is supported by a series of observations: 1) intracellular access of these antagonists is required for their activity; 2) specific, saturable binding of a radiolabeled antagonist requires the presence of CCR4; and 3) through engineering receptor chimeras by reciprocal transfer of C-terminal domains between CCR4 and CCR5, compound binding and the selective structure-activity relationships for antagonism of these receptors seem to be associated with the integrity of that intracellular region. Published antagonists from other chemical series do not seem to bind to the novel site, and their interaction with either CCR4 or CCR5 is not affected by alteration of the C-terminal domain. The precise location of the proposed binding site remains to be determined, but the known close association of the C-terminal domain, including helix 8, as a proposed intracellular region that interacts with transduction proteins (e.g., G proteins and beta-arrestin) suggests that this could be a generic allosteric site for chemokine receptors and perhaps more broadly for class A G protein-coupled receptors. The existence of such a site that can be targeted for drug discovery has implications for screening assays for receptor antagonists, which would need, therefore, to consider compound properties for access to this intracellular site.
Jaehne, E J; Baune, B T
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.
Alencar, A.; Kruikemeier, S.
This study investigates to what extent audiovisual infotainment features can be found in the narrative structure of television news in three European countries news. Content analysis included a sample of 639 news reports (or reporter packages) aired in the first three weeks of September 2013, in six
Trilling, D.; Schönbach, K.
In the ongoing debate on the role of the Internet in public discourse, it is often assumed that online news fundamentally changes mass communication. But is there a relationship between online news use and a differentiation in overall news consumption patterns? The results of a large-scale survey co
Holland, Wade B.
An issue of "Soviet Cybernetics: Recent News Items" consists of English translations of the leading recent Soviet contributions to the study of cybernetics. Articles deal with cybernetics in the 21st Century; the Soviet State Committee on Science and Technology; economic reforms in Rudnev's ministry; an interview with Rudnev; Dnepr-2; Dnepr-2…
Cohesion embodies the non-structural resources in English discourse and indicates the latent continuity existing in the text.On the basis of cohesion theory,this paper analyzes textual cohesion of the selected news reports form BBC website,in order to explore the way of structuring the text and realizing the meaning of the text.
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...
Bollerslev, Tim; Li, Jia; Xue, Yuan
We provide new empirical evidence for the way in which financial markets process information. Our results are based on high-frequency intraday data along with new econometric techniques for making inference on the relationship between trading intensity and spot volatility around public news...
Gumus, Agah; Ozad, Bahire
Over the last decade, comparisons of the effects of the traditional news media and the Internet have been made in relation to comprehension and remembering. This study aims at assessing the effects of single and compound presentational elements, and making predictions for the future. One of the two main aims of this study is to measure…
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 th...... challenges the conventional routines and symbolic power of journalism as a place where, metaphorically, people can come together....
This column is designed to give JCE readers a few highlights from Chem 13 News, a monthly publication for chemistry educators from the University of Waterloo in Ontario, Canada, and provides annotations describing a particular activity or a variety of sources from which new and creative ideas can be extracted.
Lefevere, J.; De Swert, K.; Walgrave, S.
Common people that are apparently randomly selected by journalists to illustrate a news story (popular exemplars) have a substantial effect on what the audience think about the issue. This effect may be partly due to the mere fact that popular exemplars attract attention and act as attention command
This thesis presents an empirical analysis and normative theoretical evaluation of Reddit, a social news website, focusing on its coverage of the 2012 US presidential election campaign. It explores the site's structural features and organization, and evaluates its coverage by standards derived from...
Hermes, Joke; Graaf, Christa de
This paper will query whether a dedicated news platform can attune to young people’s civic needs? That is to ask: can this be a space that follows a social media logic of conversation and ‘give and take’ – with producers and consumers changing roles or even losing the distinction? How could and woul
to the news. This chapter outlines the importance of space and place when it comes to audiences/users of journalism and the gradual recognition of this in digital journalism studies, with an eye to highlighting pertinent research trajectories. It first explores how the everyday digital geographies...
Menkveld, Albert J.; Sarkar, Asani; Wel, van der Michel
Signed customer order flow correlates with permanent price changes in equity and nonequity markets. We exploit macro news events in the 30Y treasury futures market to identify causality from customer flow to riskfree rates. We remove the positive feedback trading part and establish that, in the 15 m
Broersma, Marcel; Graham, Todd
This paper both theoretically and empirically explores how people formerly known as sources use Twitter to strategically generate news coverage and to set the public agenda. Based on a large scale content analysis (2007-2013) of newspaper coverage in both tabloids and broadsheets in the UK and the N
Chan, Joseph Man; Lee, Chin-Chuan
Reporters in Hong Kong who were working for 21 Chinese-language newspapers were mailed questionnaires to elicit information on the following: how news organizations in a highly politicized environment exercise control on recruitment, policy direction with regard to the coverage of conflicting issues, and the resolution of possible conflicts…
Dias, Lauren; Chabner, Bruce A; Lynch, Thomas J; Penson, Richard T
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH), founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient, support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. Clinicians in the field of oncology are unavoidably forced to break bad news. The Schwartz Center Rounds focuses on issues of communication between patients and their caregivers, one of the most difficult aspects of which is breaking bad news. The invited patient, a woman who had been living with a low-grade cancer for many years, spoke about her experiences both as a person living with cancer and as the daughter of a patient diagnosed with cancer. Her father's suicide, precipitated by being told his diagnosis, puts the horror of receiving bad news into stark relief. She provides a fascinating account of how she proactively adjusted to her diagnosis, and fought for optimal quality of life. This article discusses issues of support, abandonment, and how hope is conveyed, and reviews the literature that informs good clinical practice in breaking bad news.
Full Text Available CCL25/CCR9 is a non-promiscuous chemokine/receptor pair and a key regulator of leukocyte migration to the small intestine. We investigated here whether CCL25/CCR9 interactions also play a role in the regulation of inflammatory responses in the large intestine.Acute inflammation and recovery in wild-type (WT and CCR9(-/- mice was studied in a model of dextran sulfate sodium (DSS-induced colitis. Distribution studies and phenotypic characterization of dendritic cell subsets and macrophage were performed by flow cytometry. Inflammatory bowel disease (IBD scores were assessed and expression of inflammatory cytokines was studied at the mRNA and the protein level.CCL25 and CCR9 are both expressed in the large intestine and are upregulated during DSS colitis. CCR9(-/- mice are more susceptible to DSS colitis than WT littermate controls as shown by higher mortality, increased IBD score and delayed recovery. During recovery, the CCR9(-/- colonic mucosa is characterized by the accumulation of activated macrophages and elevated levels of Th1/Th17 inflammatory cytokines. Activated plasmacytoid dendritic cells (DCs accumulate in mesenteric lymph nodes (MLNs of CCR9(-/- animals, altering the local ratio of DC subsets. Upon re-stimulation, T cells isolated from these MLNs secrete significantly higher levels of TNFα, IFNγ, IL2, IL-6 and IL-17A while down modulating IL-10 production.Our results demonstrate that CCL25/CCR9 interactions regulate inflammatory immune responses in the large intestinal mucosa by balancing different subsets of dendritic cells. These findings have important implications for the use of CCR9-inhibitors in therapy of human IBD as they indicate a potential risk for patients with large intestinal inflammation.
Full Text Available Recent studies have shown that bone marrow-derived fibroblasts contribute significantly to the pathogenesis of renal fibrosis. However, the molecular mechanisms underlying the recruitment of bone marrow-derived fibroblasts into the kidney are incompletely understood. Bone marrow-derived fibroblasts express the chemokine receptor--CCR2. In this study, we tested the hypothesis that CCR2 participates in the recruitment of fibroblasts into the kidney during the development of renal fibrosis. Bone marrow-derived collagen-expressing GFP⁺ fibroblasts were detected in the obstructed kidneys of chimeric mice transplanted with donor bone marrow from collagen α1(I-GFP reporter mice. These bone marrow-derived fibroblasts expressed PDGFR-β and CCR2. CCR2 knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors expressing the hematopoietic marker-CD45 and the mesenchymal markers-PDGFR-β or procollagen I in the obstructed kidneys compared with wild-type mice. Furthermore, CCR2 knockout mice displayed fewer bone marrow-derived myofibroblasts and expressed less α-SMA or FSP-1 in the obstructed kidneys compared with wild-type mice. Consistent with these findings, genetic deletion of CCR2 inhibited total collagen deposition and suppressed expression of collagen I and fibronectin. Moreover, genetic deletion of CCR2 inhibits MCP-1 and CXCL16 gene expression associated with a reduction of inflammatory cytokine expression and macrophage infiltration, suggesting a linear interaction between two chemokines/ligand receptors in tubular epithelial cells. Taken together, our results demonstrate that CCR2 signaling plays an important role in the pathogenesis of renal fibrosis through regulation of bone marrow-derived fibroblasts. These data suggest that inhibition of CCR2 signaling could constitute a novel therapeutic approach for fibrotic kidney disease.
Orr, Jeb S; Kennedy, Arion J; Hill, Andrea A; Anderson-Baucum, Emily K; Hubler, Merla J; Hasty, Alyssa H
The mechanism by which macrophages and other immune cells accumulate in adipose tissue (AT) has been an area of intense investigation over the past decade. Several different chemokines and their cognate receptors have been studied for their role as chemoattractants in promoting recruitment of immune cells to AT However, it is also possible that chemoattractants known to promote clearance of immune cells from tissues to regional lymph nodes might be a critical component to overall AT immune homeostasis. In this study, we evaluated whether CCR7 influences AT macrophage (ATM) or T-cell (ATT) accumulation. CCR7(-/-) and littermate wild-type (WT) mice were placed on low-fat diet (LFD) or high-fat diet (HFD) for 16 weeks. CCR7 deficiency did not impact HFD-induced weight gain, hepatic steatosis, or glucose intolerance. Although lean CCR7(-/-) mice had an increased proportion of alternatively activated ATMs, there were no differences in ATM accumulation or polarization between HFD-fed CCR7(-/-) mice and their WT counterparts. However, CCR7 deficiency did lead to the preferential accumulation of CD8(+) ATT cells, which was further exacerbated by HFD feeding. Finally, expression of inflammatory cytokines/chemokines, such as Tnf, Il6, Il1β, Ccl2, and Ccl3, was equally elevated in AT by HFD feeding in CCR7(-/-) and WT mice, while Ifng and Il18 were elevated by HFD feeding in CCR7(-/-) but not in WT mice. Together, these data suggest that CCR7 plays a role in CD8(+)ATT cell egress, but does not influence ATM accumulation or the metabolic impact of diet-induced obesity.
Full Text Available Background and objective It has been proven that hypoxia could promote tumor cells invasion and metastasis by different mechanisms, but the relationship between hypoxia and CCR7 have not been reported. The aim of this investigate is to evaluate the effects of hypoxia on the expression of CCR7 and the invasiveness of lung adenocarcinoma A549 cells. Methods A549 cells were incubated at either normoxia (37 ℃, 5%CO2, 21%O2 or hypoxia(37 ℃, 5%CO2, 1%O2 condition for 4 h,12 h, 24 h. The expressions of CCR7 mRNA and protein levels were observed by RT-PCR and Western blotting; Cells invasiveness was measured by matrigel invasion assay. Results RT-PCR and Western blotting showed that the expression of CCR7 was detected in lung adenocarcinoma A549 cells, CCR7 mRNA and protein expression level were increased with culture time along either in normoxia or hypoxia condition; Furthermore,compared with normoxia group, the CCR7 mRNA and protein expression level in hypoxia group was increased (P <0.01.The results of Transwell invasion showed that The number of invasive cells was significantly increased in hypoxia group(t =0.006, P <0.01 and A549 cells invasive ability was inhibited after add anti-CCR7 Ab to culture medium (t =0.09, P <0.01. Conclusion The results suggest that hypoxia plays an important role in the augmentation of the CCR7 expression and invasiveness of A549 cells. Invasion of A549 cells in hypoxia condition correlated with CCR7 expression level.
Moran, Timothy P; Nakano, Hideki; Kondilis-Mangum, Hrisavgi D; Wade, Paul A; Cook, Donald N
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.
Dybas, C. L.
As Rachel Carson wrote in her 1956 book, The Sense of Wonder, it's important for everyone to develop an appreciation of "land, sea and sky." One of the best ways of getting the word out to the public about these realms is through the media. How do scientists capture the interest of the press in a society with a seemingly shorter and shorter attention span? Studies show that as the amount of scientific jargon and number of complex concepts in a news story increase, "filter-feeding" by the public of that news declines. When scientific jargon/complex concepts are few, the public "consumes" much more news. These results also apply to news story headlines: shorter headlines get the most interest. Based on these findings, one organization has started an experiment in "scientific speed dating": giving presenters three minutes to discuss results. They may have discovered something: news coverage of the research has been excellent. In today's world, conveying news about the geosciences in haiku-short form may be the best way of relating the wonders of land, sea and sky.
As an important component of experiential function in systemic functional grammar proposed by M.A.K Halliday, transitivity is a major tool of describing and analyzing clause or discourse. The paper will mainly make a detailed analysis to news discourse based on transitivity. By discussing the features of news and the application of transitivity in news discourse, the paper aims to reveal the regularity and characteristics of news discourse on the distribution of process types and provide a new function-al perspective for analysis of news discourse.
News is closely related with people’s lives and has the function of describing facts and conveying messages to the pub⁃lic. News is required to be true, swift and accurate and has formed its own language system. Based on the experiential function theory of functional grammar and its main device—transitivity, this thesis analyzes the transitivity processes in the two disaster news samples and two celebrity news samples from New York Times. It will further prove the applicability and operability of transi⁃tivity theory in news analysis.
As a special type of writing, news report has attracted more and more attention in different countries. Many people have developed an interest in reading English news, which provides them with timely information about important happenings around the world. Under the frame work of Systemic-Functional Grammar, based on English news headlines, the theme-rheme structure of English headlines is systemically analyzed in this thesis. Some detailed researches are made to investigate the influence of the Theme-rheme Structure in English news headlines. Then the news headline as well as its contents could be understood and enjoyed while reading newspaper.
Noticias del Cosmos is a collection of web pages within the Astronomical Observatory of the University of Valencia's website where we publish short daily summaries of astronomical press releases. Most, if not all of, the releases are originally written in English, and often Spanish readers may find them difficult to understand because not many people are familiar with the scientific language employed in these releases. Noticias del Cosmos has two principal aims. First, we want to communicate the latest astronomical news on a daily basis to a wide Spanish-speaking public who would otherwise not be able to read them because of the language barrier. Second, daily news can be used as a tool to introduce the astronomical topics of the school curriculum in a more immediate and relevant way. Most of the students at school have not yet reached a good enough level in their knowledge of English to fully understand a press release, and Noticias del Cosmos offers them and their teachers this news in their mother tongue. During the regular programme of school visits at the Observatory we use the news as a means of showing that there is still a lot to be discovered. So far the visits to the website have been growing steadily. Between June 2003 and June 2007 we had more than 30,000 visits (excluding 2006). More than 50% of the visits come from Spain, followed by visitors from South and Central America. The feedback we have received from teachers so far has been very positive, showing the usefulness of news items in the classroom when teaching astronomy.