A novel mechanism for binding of galactose-terminated glycans by the C-type carbohydrate recognition domain in blood dendritic cell antigen 2

Blood dendritic cell antigen 2 (BDCA-2; also designated CLEC4C or CD303) is uniquely expressed on plasmacytoid dendritic cells. Stimulation of BDCA-2 with antibodies leads to an anti-inflammatory response in these cells, but the natural ligands for the receptor are not known. The C-type carbohydrate recognition domain in the extracellular portion of BDCA-2 contains a signature motif typical of C-type animal lectins that bind mannose, glucose, or GlcNAc, yet it has been reported that BDCA-2 binds selectively to galactose-terminated, biantennary N-linked glycans. A combination of glycan array analysis and binding competition studies with monosaccharides and natural and synthetic oligosaccharides have been used to define the binding epitope for BDCA-2 as the trisaccharide Galβ1–3/4GlcNAcβ1–2Man. X-ray crystallography and mutagenesis studies show that mannose is ligated to the conserved Ca2+ in the primary binding site that is characteristic of C-type carbohydrate recognition domains, and the GlcNAc and galactose residues make additional interactions in a wide, shallow groove adjacent to the primary binding site. As predicted from these studies, BDCA-2 binds to IgG, which bears galactose-terminated glycans that are not commonly found attached to other serum glycoproteins. Thus, BDCA-2 has the potential to serve as a previously unrecognized immunoglobulin Fc receptor

Mathematical models of magnetospheric convection and its coupling to the ionosphere

Mathematical models of magnetospheric convection and its coupling to ionospher

Common Polymorphisms in Human Langerin Change Specificity for Glycan Ligands

Langerin, a C-type lectin on Langerhans cells, mediates carbohydrate-dependent uptake of pathogens in the first step of antigen presentation to the adaptive immune system. Langerin binds a diverse range of carbohydrates including high mannose structures, fucosylated blood group antigens, and glycans with terminal 6-sulfated galactose. Mutagenesis and quantitative binding assays indicate that salt bridges between the sulfate group and two lysine residues compensate for the nonoptimal binding of galactose at the primary Ca(2+) site. A commonly occurring single nucleotide polymorphism (SNP) in human langerin results in change of one of these lysine residues, Lys-313, to isoleucine. Glycan array screening reveals that this amino acid change abolishes binding to oligosaccharides with terminal 6SO(4)-Gal and enhances binding to oligosaccharides with terminal GlcNAc residues. Structural analysis shows that enhanced binding to GlcNAc may result from Ile-313 packing against the N-acetyl group. The K313I polymorphism is tightly linked to another SNP that results in the change N288D, which reduces affinity for glycan ligands by destabilizing the Ca(2+)-binding site. Langerin with Asp-288 and Ile-313 shows no binding to 6SO(4)-Gal-terminated glycans and increased binding to GlcNAc-terminated structures, but overall decreased binding to glycans. Altered langerin function in individuals with the linked N288D and K313I polymorphisms may affect susceptibility to infection by microorganisms

A systematic review and meta-analysis of studies evaluating the performance and operational characteristics of dual point-of-care tests for HIV and syphilis.

BACKGROUND: Mother-to-child transmission (MTCT) of syphilis and HIV continue to be important yet preventable causes of perinatal and infant morbidity and mortality. OBJECTIVES: To systematically review, critically appraise and perform a meta-analysis to evaluate the operational characteristics of dual rapid diagnostic tests (RDTs) for HIV/syphilis and evaluate whether they are cost effective, acceptable and easy to use. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched seven electronic bibliographic databases from 2012 to December 2016 with no language restrictions. Search keywords included HIV, syphilis and diagnosis. REVIEW METHODS: We included studies that evaluated the operational characteristics of dual HIV/syphilis RDTs. Outcomes included diagnostic test accuracy, cost effectiveness, ease of use and interpretation and acceptability. All studies were assessed against quality criteria and assessed for risk of bias. RESULTS: Of 1914 identified papers, 18 were included for the meta-analysis of diagnostic accuracy for HIV and syphilis. All diagnostic accuracy evaluation studies showed a very high sensitivity and specificity for HIV and a lower, yet adequate, sensitivity and specificity for syphilis, with some variation among types of test. Dual screening for HIV and syphilis was more cost effective than single rapid tests for HIV and syphilis and prevented more adverse pregnancy outcomes. Qualitative data suggested dual RDTs were highly acceptable to clients, who cited time to result, cost and the requirement of a single finger prick as important characteristics of dual RDTs. CONCLUSION: The results of this systematic review and meta-analysis can be used by policy-makers and national programme managers who are considering implementing dual RDTs for HIV and syphilis. TRIAL REGISTRATION NUMBER: PROSPERO 2016:CRD42016049168

Tasmania’s child and family centres: a place-based early childhood services model for families and children from pregnancy to age five

Tasmania’s child and family centres (Centres) provide a single entry point to early childhood services (ECS) for children and families living in amongst the most disadvantaged communities in Australia. This study investigated the impact of Centres on parents’ use and experiences of ECS using a mixed methods approach. The results showed that Centre users made more use of ECS than did non-users. Centre users also rated their experiences of ECS more positively than non-users. For example, Centre users were more likely to report that ECS were convenient and close, committed to helping, and worked closely with one another. Centre users identified Centres as informal, accessible, responsive, nonjudgemental and supportive places where they felt valued, respected and safe. Parents experienced Centres as welcoming places that were helping them to develop positive child, family, school and community connections. These qualities appeared critical for facilitating parental access and engagement in ECS

Outer zone electrons

Spatial and temporal behavior of high energy trapped electrons in outer zone of magnetospher

Monetary Policy and Polish Labour Market in the years 1999 - 2008

This article sets out to analyse how the monetary policy pursued by the National Bank of Poland (NBP) determined the labour market situation in the country in the decade 1999-2008. The article consists of introduction as well as five sections. Section one discusses NBP's strategy of monetary policy in the defined period against monetary strategies implemented in other countries. Section two uses the growth rates of money supply and of real GDP to verify whether the primary purpose of monetary policy, i.e. the inflationary target, was achieved. Section three generally characterises the country's labour market using the levels and dynamics of employment and of unemployment. Section four discusses major instruments of NBP's monetary policy, mainly analysing changes in the central bank's interest rates and their effect on the economic situation and on the labour market. The article concludes with a summation providing synthetic conclusions.Celem artykułu jest analiza wpływu polityki monetarnej Narodowego Banku Polskiego (NBP) na sytuację na rynku pracy w Polsce w ciągu dekady obejmującej lata 1999-2008. Opracowanie składa się z wprowadzenia oraz pięciu części. W pierwszej z nich omówiona została strategia polityki monetarnej NBP w badanym okresie wraz z porównaniem ze strategią przyjmowaną w innych krajach. W części drugiej sprawdzono, czy realizowany był podstawowy cel polityki monetarnej, czyli cel inflacyjny, w kontekście kształtowania się stóp wzrostu podaży pieniądza oraz realnego PKB. W punkcie kolejnym ukazana została ogólna charakterystyka rynku pracy na podstawie kształtowania się poziomu i dynamiki zatrudnienia oraz bezrobocia. W części czwartej omówiono podstawowe instrumenty polityki pieniężnej NBP. Uwaga skoncentrowana została głównie na analizie zmian stóp procentowych banku centralnego oraz ich wpływu na sytuację gospodarczą i rynek pracy. Całość zamknięta została podsumowaniem, w którym zawarto syntetyczne wnioski końcowe

A Fast Na+/Ca2+-Based Action Potential in a Marine Diatom

BACKGROUND:Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS:The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. CONCLUSIONS/SIGNIFICANCE:This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and successful marine protists