Human intrahepatic ILC2 are IL-13^*positive Amphiregulin^*positive and their frequency correlates with Model of End stage Liver Disease score

Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue.Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function.All three ILC subsets were present in the human liver, with the ILC1 (CRTH2negCD117neg) subset constituting around 70% of intrahepatic ILCs. Both NCRpos (NKp44+) and NCRneg ILC3 (CRTH2negCD117pos) subsets were also detected. ILC2 (CRTH2pos) frequency correlated with disease severity measured by model of end stage liver disease (MELD) scoring leading us to study this subset in more detail. ILC2 displayed a tissue resident CD69+ CD161++ phenotype and expressed chemokine receptor CCR6 allowing them to respond to CCL20 secreted by cholangiocytes and stellate cells. ILC2 expressed integrins VLA-5 and VLA-6 and the IL-2 and IL-7 cytokine receptors CD25 and CD127 although IL-2 and IL-7 were barely detectable in inflamed liver tissue. Although biliary epithelial cells secrete IL-33, intrahepatic ILC2 had low expression of the ST2 receptor. Intrahepatic ILC2 secreted the immunoregulatory and repair cytokines IL-13 and amphiregulin.Intrahepatic ILC2 express receptors allowing them to be recruited to bile ducts in inflamed portal tracts. Their frequencies increased with worsening liver function. Their secretion of IL-13 and amphiregulin suggests they may be recruited to promote resolution and repair and thereby they may contribute to ongoing fibrogenesis in liver disease

Extreme Ultraviolet Transient Grating Measurement of Insulator-Metal Transition Dynamics in VO2

We demonstrate spectrally resolved transient grating (TG) spectroscopy in the extreme ultraviolet (EUV) near the M-edge of vanadium dioxide. Time-dependent and broadband EUV-TG measurements separate the index of refraction change due to the insulator to metal transition from purely acoustic effects

Broadband extreme ultraviolet probing of transient gratings in vanadium dioxide

Nonlinear spectroscopy in the extreme ultraviolet (EUV) and soft x-ray spectral range offers the opportunity for element selective probing of ultrafast dynamics using core-valence transitions (Mukamel et al., Acc. Chem. Res. 42, 553 (2009)). We demonstrate a step on this path showing core-valence sensitivity in transient grating spectroscopy with EUV probing. We study the optically induced insulator-to-metal transition (IMT) of a VO2 film with EUV diffraction from the optically excited sample. The VO2 exhibits a change in the 3p-3d resonance of V accompanied by an acoustic response. Due to the broadband probing we are able to separate the two features. (C) 2015 Optical Society of Americ

Metal-to-ligand and ligand-to-metal charge transfer in thin films of Prussian blue analogues investigated by X-ray absorption spectroscopy

A series of thin films of Prussian blue analogues is investigated by X-ray absorption spectroscopy (XAS) at the Fe, Co and Mn L(2,3)-edges. The ligand field multiplet theory enables us to examine accurately the electronic structure of these materials. Experimental XAS spectra of CoFe Prussian blue analogues are successfully reproduced using a ground state configuration including metal-toligand (MLCT) and ligand-to-metal charge transfer (LMCT) at the Co and Fe L(2,3)-edges. In particular, a huge improvement is achieved for satellite peaks at the Co(III) L(2,3)-edges compared to previous calculations in the literature based on LMCT effects only. On the other hand, XAS spectra of MnFe analogues synthesized for the first time, can be reproduced conveniently by taking into account either MLCT or LMCT depending on the conditions of the sample preparation. For each thin film, the proportion of the different oxidation states of Co, Fe and Mn is evaluated. Unexpectedly, this analysis reveals the presence of a significant amount of a reduced phase, which turns out to be strongly dependent on the sample synthesis and storage conditions

QTL mapping and successful introgression of the spring wheat-derived QTL Fhb1 for Fusarium head blight resistance in three European triticale populations

Key message The spring wheat-derived QTL Fhb1 was successfully introgressed into triticale and resulted in significantly improved FHB resistance in the three triticale mapping populations. Fusarium head blight (FHB) is a major problem in cereal production particularly because of mycotoxin contaminations. Here we characterized the resistance to FHB in triticale breeding material harboring resistance factors from bread wheat. A highly FHB-resistant experimental line which derives from a triticale x wheat cross was crossed to several modern triticale cultivars. Three populations of recombinant inbred lines were generated and evaluated in field experiments for FHB resistance using spray inoculations during four seasons and were genotyped with genotyping-by-sequencing and SSR markers. FHB severity was assessed in the field by visual scorings and on the harvested grain samples using digital picture analysis for quantifying the whitened kernel surface (WKS). Four QTLs with major effects on FHB resistance were identified, mapping to chromosomes 2B, 3B, 5R, and 7A. Those QTLs were detectable with both Fusarium severity traits. Measuring of WKS allows easy and fast grain symptom quantification and appears as an effective scoring tool for FHB resistance. The QTL on 3B collocated with Fhb1, and the QTL on 5R with the dwarfing gene Ddw1. This is the first report demonstrating the successful introgression of Fhb1 into triticale. It comprises a significant step forward for enhancing FHB resistance in this crop

Whitened kernel surface: A fast and reliable method for assessing fusarium severity on cereal grains by digital picture analysis

International audienceFusarium head blight (FHB) is a cereal disease of major importance responsible for yield losses and mycotoxin contaminations in grains. Here, we introduce a new measurement approach to quantify FHB severity on grains based on the evaluation of the whitened kernel surface (WKS) using digital image analysis. The applicability of WKS was assessed on two bread wheat and one triticale grain sample sets (265 samples). Pearson correlation coefficients between Fusarium-damaged kernels (FDK) and WKS range from r = 0.77 to r = 0.81 and from r = 0.61 to r = 0.86 for the correlation between deoxynivalenol (DON) content and WKS. This new scoring method facilitates fast and reliable assessment of the resistance to kernel infection and shows significant correlation with mycotoxin content. WKS can be automated and does not suffer from the "human factor" inherent to visual scorings. As a low-cost and fast approach, this method appears particularly attractive for breeding and genetic analysis of FHB resistance where typically large numbers of experimental lines need to be evaluated, and for which WKS is suggested as an alternative to visual FDK scorings

Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins

Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing–proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein, owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence factors that act by inhibiting TLR- and MyD88-specific signaling, thus suppressing innate immunity and increasing virulence

Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus

NADPH oxidase 4 (Nox4) has recently been implicated as driving force in cellular senescence. Thus, there is growing interest to develop Nox4 inhibitors, which might be valuable agents for cosmeceutical applications. Alpine plants represent a valuable source for the identification of novel bioactive natural products with anti-ageing effects, especially substances that protect plants against UV radiation, which is also known to contribute to the ageing of human skin. Therefore, the aim of this study was to identify novel Nox4 inhibitors from alpine plants. Within an initial screening of extracts of alpine plants on their ability to inhibit Nox4 activity in HEK cells, the methanolic extract of the subaerial parts of Lycopus europaeus showed a strong inhibition of Nox4 (81% chemiluminescence quenching) and a simultaneously high cell viability (91% vitality). Rosmarinic acid was isolated and identified as the major compound in this bioactive extract. It showed a dose dependent inhibitory activity on Nox4 with an IC50 of 1 µM. Moreover, it also showed a significant inhibitory activity on Nox2 in the low micromolar range, whereas no inhibition of Nox5 was detected. Further investigations confirmed that the observed effects of rosmarinic acid on Nox2 and Nox4 are real inhibitory activities, and not due to ROS scavenging effects. Therefore, L. europaeus, which we demonstrated to be a good source of rosmarinic acid, has great potential for usage in cosmeceutical products with anti-ageing activity