920 research outputs found

    Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

    Get PDF
    It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions

    A specific case in the classification of woods by FTIR and chemometric: discrimination of Fagales from Malpighiales

    Get PDF
    Fourier transform infrared (FTIR) spectroscopic data was used to classify wood samples from nine species within the Fagales and Malpighiales using a range of multivariate statistical methods. Taxonomic classification of the family Fagaceae and Betulaceae from Angiosperm Phylogenetic System Classification (APG II System) was successfully performed using supervised pattern recognition techniques. A methodology for wood sample discrimination was developed using both sapwood and heartwood samples. Ten and eight biomarkers emerged from the dataset to discriminate order and family, respectively. In the species studied FTIR in combination with multivariate analysis highlighted significant chemical differences in hemicelluloses, cellulose and guaiacyl (lignin) and shows promise as a suitable approach for wood sample classification

    Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

    Get PDF
    NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

    The influence of socio-economic and surveillance characteristics on breast cancer survival: a French population-based study

    Get PDF
    Survival data on female invasive breast cancer with 9-year follow-up from five French cancer registries were analysed by logistic regression for prognostic factors of cancer stage. The Kaplan–Meier method and log-rank test were used to estimate and compare the overall survival probability at 5 and 7 years, and at the endpoint. The Cox regression model was used for multivariate analysis. County of residence, age group, occupational status, mammographic surveillance, gynaecological prevention consultations and the diagnosis mammography, whether within a screening framework or not, were independent prognostic factors of survival. Moreover, for the same age group, and only for cancers T2 and/or N+ (whether 1, 2 or 3) and M0, the prognosis was significantly better when the diagnosis mammography was done within the framework of screening. Socio-economic and surveillance characteristics are independent prognostic factors of both breast cancer stage at diagnosis and of survival. Screening mammography is an independent prognostic factor of survival

    Persistence Increases with Diversity and Connectance in Trophic Metacommunities

    Get PDF
    We are interested in understanding if metacommunity dynamics contribute to the persistence of complex spatial food webs subject to colonization-extinction dynamics. We study persistence as a measure of stability of communities within discrete patches, and ask how do species diversity, connectance, and topology influence it in spatially structured food webs.We answer this question first by identifying two general mechanisms linking topology of simple food web modules and persistence at the regional scale. We then assess the robustness of these mechanisms to more complex food webs with simulations based on randomly created and empirical webs found in the literature. We find that linkage proximity to primary producers and food web diversity generate a positive relationship between complexity and persistence in spatial food webs. The comparison between empirical and randomly created food webs reveal that the most important element for food web persistence under spatial colonization-extinction dynamics is the degree distribution: the number of prey species per consumer is more important than their identity.With a simple set of rules governing patch colonization and extinction, we have predicted that diversity and connectance promote persistence at the regional scale. The strength of our approach is that it reconciles the effect of complexity on stability at the local and the regional scale. Even if complex food webs are locally prone to extinction, we have shown their complexity could also promote their persistence through regional dynamics. The framework we presented here offers a novel and simple approach to understand the complexity of spatial food webs

    “Beyond words”: a researcher’s guide to using photo elicitation in psychology

    Get PDF
    The use of photo elicitation is limited within the field of psychology despite its theoretical and practical potential. It offers significant benefits as a qualitative method that could present a new and interesting way of exploring previously understood topics within the discipline. Within our discussions, we present a Step-by-Step guide in which we outline the key practical stages, as well as ethical assurances involved in photo elicitation research, using our ongoing research as an illustrative example. It is intended that this could be used as a model of good practice for developing research paradigms beyond those typically used within the psychology discipline

    Free Will & Empirical Arguments for Epiphenomenalism

    Get PDF
    While philosophers have worried about mental causation for centuries, worries about the causal relevance of conscious phenomena are also increasingly featuring in neuroscientific literature. Neuroscientists have regarded the threat of epiphenomenalism as interesting primarily because they have supposed that it entails free will scepticism. However, the steps that get us from a premise about the causal irrelevance of conscious phenomena to a conclusion about free will are not entirely clear. In fact, if we examine popular philosophical accounts of free will, we find, for the most part, nothing to suggest that free will is inconsistent with the presence of unconscious neural precursors to choices. It is only if we adopt highly non-naturalistic assumptions about the mind (e.g. if we embrace Cartesian dualism and locate free choice in the non-physical realm) that it seems plausible to suppose that the neuroscientific data generates a threat to free will

    The association between socioeconomic status and traditional chinese medicine use among children in Taiwan

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Traditional Chinese medicine (TCM) utilization is common in Asian countries. Limited studies are available on the socioeconomic status (SES) associated with TCM use among the pediatric population. We report on the association between SES and TCM use among children and adolescents in Taiwan.</p> <p>Methods</p> <p>A National Health Interview Survey was conducted in Taiwan in 2001 that included 5,971 children and adolescents. We assessed the children's SES using the head of household's education, occupation and income. This information was used to calculate pediatric SES scores, which in turn were divided into quartiles. Children and adolescents who visited TCM in the past month were defined as TCM users.</p> <p>Results</p> <p>Compared to children in the second SES quartile, children in the fourth SES quartile had a higher average number of TCM visits (0.12 vs. 0.06 visits, p = 0.027) and higher TCM use prevalence (5.0% vs. 3.6%, p = 0.024) within the past month. The adjusted odds ratio (OR) for TCM use was higher for children in the fourth SES quartile than for those in the first SES quartile (OR 1.49; 95% confidence interval [CI] 1.02-2.17). The corresponding OR was 2.17 for girls (95% CI 1.24-3.78). The highest-SES girls (aged 10-18 years) were most likely to visit TCM practices (OR 2.47; 95% CI 1.25-4.90).</p> <p>Conclusions</p> <p>Children and adolescents with high SES were more likely to use TCM and especially girls aged 10-18 years. Our findings point to the high use of complementary and alternative medicine among children and adolescents.</p
    corecore