A guide to chemokines and their receptors

The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G‐protein coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells (leukocytes). Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behaviour, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many non‐leukocytic cell types. Chemokines are profoundly affected by post‐translational modification, by interaction with the extracellular matrix (ECM), and by binding to heptahelical ‘atypical’ chemokine receptors that regulate chemokine localisation and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarises the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focussing particularly on their ability to direct leukocyte migration

Symmetry breaking in crossed magnetic and electric fields

We present the first observations of cylindrical symmetry breaking in highly excited diamagnetic hydrogen with a small crossed electric field, and we give a semiclassical interpretation of this effect. As the small perpendicular electric field is added, the recurrence strengths of closed orbits decrease smoothly to a minimum, and revive again. This phenomenon, caused by interference among the electron waves that return to the nucleus, can be computed from the azimuthal dependence of the classical closed orbits.Comment: 4 page REVTeX file including 5 postscript files (using psfig) Accepted for publication in Physical Review Letters. Difference from earlier preprint: we have discovered the cause of the earlier apparent discrepancy between experiment and theory and now achieve excellent agreemen

Perspectives of primary health care staff on the implementation of a sexual health quality improvement program: A qualitative study in remote aboriginal communities in Australia

Background: Young people living in remote Australian Aboriginal communities experience high rates of sexually transmissible infections (STIs). STRIVE (STIs in Remote communities, ImproVed and Enhanced primary care) was a cluster randomised control trial of a sexual health continuous quality improvement (CQI) program. As part of the trial, qualitative research was conducted to explore staff perceptions of the CQI components, their normalisation and integration into routine practice, and the factors which influenced these processes. Methods: In-depth semi-structured interviews were conducted with 41 clinical staff at 22 remote community clinics during 2011-2013. Normalisation process theory was used to frame the analysis of interview data and to provide insights into enablers and barriers to the integration and normalisation of the CQI program and its six specific components. Results: Of the CQI components, participants reported that the clinical data reports had the highest degree of integration and normalisation. Action plan setting, the Systems Assessment Tool, and the STRIVE coordinator role, were perceived as adding value to the program, but were less readily integrated or normalised. The remaining two components (dedicated funding for health promotion and service incentive payments) were seen as least relevant. Our analysis also highlighted factors which enabled greater integration of the CQI components. These included familiarity with CQI tools, increased accountability of health centre staff and the translation of the CQI program into guideline-driven care. The analysis also identified barriers, including high staff turnover, limited time involved in the program and competing clinical demands and programs. Conclusions: Across all of the CQI components, the clinical data reports had the highest degree of integration and normalisation. The action plans, systems assessment tool and the STRIVE coordinator role all complemented the data reports and allowed these components to be translated directly into clinical activity. To ensure their uptake, CQI programs must acknowledge local clinical guidelines, be compatible with translation into clinical activity and have managerial support. Sexual health CQI needs to align with other CQI activities, engage staff and promote accountability through the provision of clinic specific data and regular face-to-face meetings. Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12610000358044. Registered 6/05/2010. Prospectively Registered

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum

As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis

Neuron-glia crosstalk in health and disease: fractalkine and CX3CR1 take centre stage

An essential aspect of normal brain function is the bidirectional interaction and communication between neurons and neighbouring glial cells. To this end, the brain has evolved ligand–receptor partnerships that facilitate crosstalk between different cell types. The chemokine, fractalkine (FKN), is expressed on neuronal cells, and its receptor, CX(3)CR1, is predominantly expressed on microglia. This review focuses on several important functional roles for FKN/CX(3)CR1 in both health and disease of the central nervous system. It has been posited that FKN is involved in microglial infiltration of the brain during development. Microglia, in turn, are implicated in the developmental synaptic pruning that occurs during brain maturation. The abundance of FKN on mature hippocampal neurons suggests a homeostatic non-inflammatory role in mechanisms of learning and memory. There is substantial evidence describing a role for FKN in hippocampal synaptic plasticity. FKN, on the one hand, appears to prevent excess microglial activation in the absence of injury while promoting activation of microglia and astrocytes during inflammatory episodes. Thus, FKN appears to be neuroprotective in some settings, whereas it contributes to neuronal damage in others. Many progressive neuroinflammatory disorders that are associated with increased microglial activation, such as Alzheimer's disease, show disruption of the FKN/CX(3)CR1 communication system. Thus, targeting CX(3)CR1 receptor hyperactivation with specific antagonists in such neuroinflammatory conditions may eventually lead to novel neurotherapeutics

Requests On E-Mail: a Cross-Cultural Comparison

This study investigates differences in request e-mails written in English by Chinese English learners and native American English speakers The results show that while Chinese English learners treat e-mail communications like either formal letters or telephone conversations, native American English speakers regard e-mail communications as closer to written memos It was also found that although the native American English speakers structure their e-mail request messages in a rather direct sequence, the linguistic forms they employ to express their requests are more indirect In contrast, the Chinese English learners structure their request messages in an indirect sequence, but the linguistic forms they use to realize their requests are more direct Given this contrast, it is not surprising that some of the request samples written by Chinese English learners were judged as very impolite by the native English speaking evaluators in this study The findings of this study thus demonstrate the importance of studying requests within the overall discourse in which they occur. Studying only the linguistic forms used in phrasing the request itself, as in the studies conducted by Blum-Kulka et al (1989), cannot provide us with a full picture of the cultural differences inherent in making requestsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69055/2/10.1177_003368829802900206.pd

Patterns in Greater Sage-grouse population dynamics correspond with public grazing records at broad scales

Human land use, such as livestock grazing, can have profound yet varied effects on wildlife interacting within common ecosystems, yet our understanding of land-use effects is often generalized from short-term, local studies that may not correspond with trends at broader scales. Here we used public land records to characterize livestock grazing across Wyoming, USA, and we used Greater Sage-grouse (Centrocercus urophasianus) as a model organism to evaluate responses to livestock management. With annual counts of male Sage-grouse from 743 leks (breeding display sites) during 2004-2014, we modeled population trends in response to grazing level (represented by a relative grazing index) and timing across a gradient in vegetation productivity as measured by the Normalized Vegetation Difference Index (NDVI). We found grazing can have both positive and negative effects on Sage-grouse populations depending on the timing and level of grazing. Sage-grouse populations responded positively to higher grazing levels after peak vegetation productivity, but populations declined when similar grazing levels occurred earlier, likely reflecting the sensitivity of cool-season grasses to grazing during peak growth periods. We also found support for the hypothesis that effects of grazing management vary with local vegetation productivity. These results illustrate the importance of broad-scale analyses by revealing patterns in Sage-grouse population trends that may not be inferred from studies at finer scales, and could inform sustainable grazing management in these ecosystems

A B2B Architecture and Protocol for Researchers Cooperation

Acknowledgement: Electronic version of an article published as International Journal of Cooperative Information Systems, Volume 22, Issue 02, 2013, DOI: 10.1142/S021884301350010X © World Scientific Publishing Company http://www.worldscientific.com/Some works on the researchers cooperation's literature provide the key lines for building research networks and propose new protocols and standards for business to business (B2B) data exchange, but none of them explains how researchers should contact and the procedure to select the most appropriate partner of a research enterprise, institute or university. In this paper, we propose a B2B architecture and protocol between research entities, that uses ebXML protocol. The contacts for cooperation are established based on some defined parameters and an information retrieval system. We explain the information retrieval system, the researcher selection procedure, the XML-based protocol and the workflow of our proposal. We also show the information that has to be exchanged to contact other researchers. Several simulations demonstrate that our proposal is a feasible architecture and may be used to promote the research cooperation. The main purpose of this paper is to propose an efficient procedure for searching project partners.Lloret, J.; Tomás Gironés, J.; García Pineda, M.; Lacuesta Contreras, R. (2013). A B2B Architecture and Protocol for Researchers Cooperation. International Journal of Cooperative Information Systems. 22(2):1-27. doi:10.1142/S021884301350010XS127222B. Wellman and S. D. Berkowitz, Social Structures: A Network Approach (Cambridge University Press, Cambridge, 1988) pp. 19–61.Wasserman, S., & Faust, K. (1994). Social Network Analysis. doi:10.1017/cbo9780511815478Wellman, B., Salaff, J., Dimitrova, D., Garton, L., Gulia, M., & Haythornthwaite, C. (1996). Computer Networks as Social Networks: Collaborative Work, Telework, and Virtual Community. Annual Review of Sociology, 22(1), 213-238. doi:10.1146/annurev.soc.22.1.213Fulk, J., & Steinfield, C. (1990). Organizations and Communication Technology. doi:10.4135/9781483325385B. Wellman and M. Gulia, Networks in the Global Village (Westview Press, Boulder, CO, 1997) pp. 331–367.Marsden, P. V., & Campbell, K. E. (1984). Measuring Tie Strength. Social Forces, 63(2), 482-501. doi:10.1093/sf/63.2.482Wellman, B., & Wortley, S. (1990). Different Strokes from Different Folks: Community Ties and Social Support. American Journal of Sociology, 96(3), 558-588. doi:10.1086/229572Adamic, L., & Adar, E. (2005). How to search a social network. Social Networks, 27(3), 187-203. doi:10.1016/j.socnet.2005.01.007Ebel, H., Mielsch, L.-I., & Bornholdt, S. (2002). Scale-free topology of e-mail networks. Physical Review E, 66(3). doi:10.1103/physreve.66.035103Jung, J.-Y., Kim, H., & Kang, S.-H. (2006). Standards-based approaches to B2B workflow integration. Computers & Industrial Engineering, 51(2), 321-334. doi:10.1016/j.cie.2006.02.011Lloret, J., Palau, C., Boronat, F., & Tomas, J. (2008). Improving networks using group-based topologies. Computer Communications, 31(14), 3438-3450. doi:10.1016/j.comcom.2008.05.030Lloret, J., Garcia, M., Tomás, J., & Boronat, F. (2008). GBP-WAHSN: A Group-Based Protocol for Large Wireless Ad Hoc and Sensor Networks. Journal of Computer Science and Technology, 23(3), 461-480. doi:10.1007/s11390-008-9147-6Lloret, J., Garcia, M., Bri, D., & Diaz, J. R. (2009). Study and performance of a group-based Content Delivery Network. Journal of Network and Computer Applications, 32(5), 991-999. doi:10.1016/j.jnca.2009.03.008Lloret, J., Garcia, M., Tomas, J., & Sendra, S. (2010). A group-based architecture for grids. Telecommunication Systems, 46(2), 117-133. doi:10.1007/s11235-010-9279-1Lin, T.-C., & Huang, C.-C. (2010). Withholding effort in knowledge contribution: The role of social exchange and social cognitive on project teams. Information & Management, 47(3), 188-196. doi:10.1016/j.im.2010.02.001Maron, M. E., & Kuhns, J. L. (1960). On Relevance, Probabilistic Indexing and Information Retrieval. Journal of the ACM, 7(3), 216-244. doi:10.1145/321033.321035Tomás, J., Lloret, J., & Casacuberta, F. (2005). Phrase-Based Alignment Models for Statistical Machine Translation. Lecture Notes in Computer Science, 605-613. doi:10.1007/11492542_74Turel, O., & Zhang, Y. (Jenny). (2011). Should I e-collaborate with this group? A multilevel model of usage intentions. Information & Management, 48(1), 62-68. doi:10.1016/j.im.2010.12.004Okuda, T., Tanaka, E., & Kasai, T. (1976). A Method for the Correction of Garbled Words Based on the Levenshtein Metric. IEEE Transactions on Computers, C-25(2), 172-178. doi:10.1109/tc.1976.500923

Unresolved issues and new challenges in teaching English to young learners:the case of South Korea

The introduction of languages, especially English, into the primary curriculum around the world has been one of the major language-in-education policy developments in recent years. In countries where English has been compulsory for a number of years, the question arises as to what extent the numerous and well-documented challenges faced by the initial implementation of early language learning policies have been overcome and whether new challenges have arisen as policies have become consolidated. This article therefore focuses on South Korea, where English has been compulsory in primary school since 1997. The issues raised by the introduction of English into the primary curriculum are reviewed and the current situation in South Korea is investigated. The results of a mixed methods study using survey data from 125 Korean primary school teachers, together with data from a small-scale case study of one teacher are presented. The study shows that, while some of the initial problems caused by the introduction of early language learning appear to have been addressed, other challenges persist. Moreover, the data reveal the emergence of a number of new challenges faced by primary school teachers of English as they seek to implement government policy

New constraints on ΩM, ΩΛ and w from an independent set of 11 high-redshift supernovae observed with the Hubble Space Telescope

We report measurements of ΩM, ΩΛ nd w from 11 supernovae (SNe) at z = 0.36-0.86 with high-quality light curves measured using WFPC2 on the Hubble Space Telescope (HST). This is an independent set of high-redshift SNe that confirms previous SN evidence for an accelerating universe. The high-quality light curves available from photometry on WFPC2 make it possible for these 11 SNe alone to provide measurements of the cosmological parameters comparable in statistical weight to the previous results. Combined with earlier Supernova Cosmology Project data, the new SNe yield a measurement of the mass density ΩM = 0.25 -0.06+0.07 (statistical) ± 0.04 (identified systematics), or equivalently, a cosmological constant of ± = 0.75 -0.07+0.06 (statistical) ± 0.04 (identified systematics), under the assumptions of a flat universe and that the dark energy equation-of-state parameter has a constant value w = -1. When the SN results are combined with independent flat-universe measurements of ΩM from cosmic microwave background and galaxy redshift distortion data, they provide a measurement of w = -1.05-0.20+0.15 (statistical) ± 0.09 (identified systematic), if w is assumed to be constant in time. In addition to high-precision light-curve measurements, the new data offer greatly improved color measurements of the high-redshift SNe and hence improved host galaxy extinction estimates. These extinction measurements show no anomalous negative E(B-V) at high redshift. The precision of the measurements is such that it is possible to perform a host galaxy extinction correction directly for individual SNe without any assumptions or priors on the parent E(B-V) distribution. Our cosmological fits using full extinction corrections confirm that dark energy is required with P(ΩΛ \u3e 0) \u3e 0.99, a result consistent with previous and current SN analyses that rely on the identification of a low-extinction subset or prior assumptions concerning the intrinsic extinction distribution