1,132 research outputs found

    Robust modeling of human contact networks across different scales and proximity-sensing techniques

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    The problem of mapping human close-range proximity networks has been tackled using a variety of technical approaches. Wearable electronic devices, in particular, have proven to be particularly successful in a variety of settings relevant for research in social science, complex networks and infectious diseases dynamics. Each device and technology used for proximity sensing (e.g., RFIDs, Bluetooth, low-power radio or infrared communication, etc.) comes with specific biases on the close-range relations it records. Hence it is important to assess which statistical features of the empirical proximity networks are robust across different measurement techniques, and which modeling frameworks generalize well across empirical data. Here we compare time-resolved proximity networks recorded in different experimental settings and show that some important statistical features are robust across all settings considered. The observed universality calls for a simplified modeling approach. We show that one such simple model is indeed able to reproduce the main statistical distributions characterizing the empirical temporal networks

    Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

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    Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

    Macrofossils and pollen representing forests of the pre-Taupo volcanic eruption (c. 1850 yr BP) era at Pureora and Benneydale, central North Island, New Zealand.

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    Micro- and macrofossil data from the remains of forests overwhelmed and buried at Pureora and Benneydale during the Taupo eruption (c. 1850 conventional radiocarbon yr BP) were compared. Classification of relative abundance data separated the techniques, rather than the locations, because the two primary clusters comprised pollen and litter/wood. This indicates that the pollen:litter/wood within-site comparisons (Pureora and Benneydale are 20 km apart) are not reliable. Plant macrofossils represented mainly local vegetation, while pollen assemblages represented a combination of local and regional vegetation. However, using ranked abundance and presence/absence data, both macrofossils and pollen at Pureora and Benneydale indicated conifer/broadleaved forest, of similar forest type and species composition at each site. This suggests that the forests destroyed by the eruption were typical of mid-altitude west Taupo forests, and that either data set (pollen or macrofossils) would have been adequate for regional forest interpretation. The representation of c. 1850 yr BP pollen from the known buried forest taxa was generally consistent with trends determined by modern comparisons between pollen and their source vegetation, but with a few exceptions. A pollen profile from between the Mamaku Tephra (c. 7250 yr BP) and the Taupo Ignimbrite indicated that the Benneydale forest had been markedly different in species dominance compared with the forest that was destroyed during the Taupo eruption. These differences probably reflect changes in drainage, and improvements in climate and/or soil fertility over the middle Holocene

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

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    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
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