Specification of the T helper 17 (Th17) cell lineage requires a well-defined set of transcription factors, but how these integrate with posttranscriptional and epigenetic programs to regulate gene ...expression is poorly understood. Here we found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.
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•miR-155 is highly induced during mouse and human Th17 cell differentiation•Jarid2 and miR-155 are epistatic in Th17 and Treg cells•Jarid2 is required to recruit PRC2 to genomic sites in Th17 cells•Direct targets of PRC2 in Th17 cells include Il22, Il10, Il9, and Atf3
miR-155 is known to promote inflammatory Th17 cell responses, but the mechanism has been unclear. Escobar et al. find that miR-155 promotes cytokine expression in Th17 cells by repressing Jarid2 to relieve Polycomb-mediated gene silencing.
In recent years, the construct of mindfulness has gained growing attention in psychological research. However, little is known about the effects of mindfulness on interpersonal interactions and ...social relationships at work. Addressing this gap, the purpose of this study was to investigate the role of mindfulness in leader-follower relationships. Building on prior research, we hypothesize that leaders' mindfulness is reflected in a specific communication style ("mindfulness in communication"), which is positively related to followers' satisfaction with their leaders. We used nested survey data from 34 leaders and 98 followers from various organizations and tested mediation hypotheses using hierarchical linear modeling. Our hypotheses were confirmed by our data in that leaders' self-reported mindfulness showed a positive relationship with several aspects of followers' satisfaction. This relationship was fully mediated by leaders' mindfulness in communication as perceived by their followers. Our findings emphasize the potential value of mindfulness in workplace settings. They provide empirical evidence for a positive link between leaders' dispositional mindfulness and the wellbeing of their followers, indicating that mindfulness is not solely an individual resource but also fosters interpersonal skills. By examining leaders' mindfulness in communication as an explanatory process, we created additional clarification about
leaders' mindfulness relates to followers' perceptions, offering a promising starting point for measuring behavioral correlates of leader mindfulness.
Brassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs ...participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helix–loop–helix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the post-translational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
The kinetics of the restoration processes that take place during the isothermal annealing of metals for the case when the critical strain for the onset of dynamic recrystallization is reached and ...exceeded were modeled using the Cellular Automata approach. The model enables both quantitative and topographic simulations of microstructural evolution before and during metadynamic recrystallization. It allows the simulation of multi-stage deformation. It was observed that two kinds of transition between the strain-dependent and strain-independent range are possible: the first is smooth, whereas the second is oscillatory. The post-dynamic softening is shown to be weakly dependent on strain and temperature, but strongly dependent on strain rate, as has been observed in published experimental work.
PGSB (Plant Genome and Systems Biology: formerly MIPS) PlantsDB (http://pgsb.helmholtz-muenchen.de/plant/index.jsp) is a database framework for the comparative analysis and visualization of plant ...genome data. The resource has been updated with new data sets and types as well as specialized tools and interfaces to address user demands for intuitive access to complex plant genome data. In its latest incarnation, we have re-worked both the layout and navigation structure and implemented new keyword search options and a new BLAST sequence search functionality. Actively involved in corresponding sequencing consortia, PlantsDB has dedicated special efforts to the integration and visualization of complex triticeae genome data, especially for barley, wheat and rye. We enhanced CrowsNest, a tool to visualize syntenic relationships between genomes, with data from the wheat sub-genome progenitor Aegilops tauschii and added functionality to the PGSB RNASeqExpressionBrowser. GenomeZipper results were integrated for the genomes of barley, rye, wheat and perennial ryegrass and interactive access is granted through PlantsDB interfaces. Data exchange and cross-linking between PlantsDB and other plant genome databases is stimulated by the transPLANT project (http://transplantdb.eu/).
The development of Th1 lymphocytes is essential for cell-mediated immunity and resistance against intracellular pathogens. However, if left unregulated, the same response can cause serious damage to ...host tissues and lead to mortality. A number of different paracrine regulatory mechanisms involving distinct myeloid and lymphoid subpopulations have been implicated in controlling excessive secretion of inflammatory cytokines by Th1 cells. Much of this work has focused on interleukin (IL)-10, a cytokine with broad anti-inflammatory properties, one of which is to counteract the function of Th1 lymphocytes. While studying the role of IL-10 in regulating immunopathology during infection with the intracellular parasite Toxoplasma gondii, we discovered that the host-protective IL-10 derives in an autocrine manner from conventional interferon-gamma (IFN-gamma)-producing T-bet(+) Foxp3(neg) Th1 cells. In the following review, we will discuss these findings that support the general concept that production of IL-10 is an important self-regulatory function of CD4(+) T lymphocytes.
In order to remain competitive to powder metallurgy and spray forming, further improvements of a classical production route are needed and desired. This paper describes the means by which the ...intrinsic hot deformability may be improved and the temperature range of the safe hot working extended for AISI M42 super high speed steel, one of the most challenging materials with respect to hot deformability. A special hot compression procedure is described to determine appropriate soaking temperatures of as-cast and semi-wrought states. Moreover, conventional hot compression tests in the extended temperature range (850–1150°C) and strain rates range 0.001–5s−1 were carried out. The complex behaviour of carbides is discussed, which depends on the soaking temperature and time, deformation temperature and strain rate. Deformation conditions for improved crushing of initial eutectic carbides networks during the first stages of hot working are identified. Apparent activation energies for hot working in two temperature ranges and constants of the hyperbolic sine function are determined. The microstructure and respective carbides are characterised by field emission scanning electron microscope, optical microscopy, X-ray diffraction and the results compared to equilibrium thermodynamic calculations using ThermoCalc.
Many cellular processes involve the recruitment of proteins to specific membranes, which are decorated with distinctive lipids that act as docking sites. The phosphoinositides form signaling hubs, ...and we examine mechanisms underlying recruitment. We applied a physiological, quantitative, liposome microarray-based assay to measure the membrane-binding properties of 91 pleckstrin homology (PH) domains, the most common phosphoinositide-binding target. 10,514 experiments quantified the role of phosphoinositides in membrane recruitment. For most domains examined, the observed binding specificity implied cooperativity with additional signaling lipids. Analyses of PH domains with similar lipid-binding profiles identified a conserved motif, mutations in which—including some found in human cancers—induced discrete changes in binding affinities in vitro and protein mislocalization in vivo. The data set reveals cooperativity as a key mechanism for membrane recruitment and, by enabling the interpretation of disease-associated mutations, suggests avenues for the design of small molecules targeting PH domains.
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•The lipid-binding properties of 91 pleckstrin homology domains have been quantified•Over 10,000 individual protein-lipid interaction experiments have been performed•The binding specificity and affinity imply cooperativity between signaling lipids•Mutations found in cancer biopsies fine-tune lipid-binding specificities
Vonkova et al. systematically quantify the lipid-binding properties of 91 pleckstrin homology (PH) domains using a physiological, quantitative, liposome microarray-based assay. The data set reveals that cooperativity between lipids is a key mechanism for membrane recruitment of PH domains.
IL-25 (IL-17E) is a unique IL-17 family ligand that promotes Th2-skewed inflammatory responses. Intranasal administration of IL-25 into naive mice induces pulmonary inflammation similar to that seen ...in patients with allergic asthma, including increases in bronchoalveolar lavage fluid eosinophils, bronchoalveolar lavage fluid IL-5 and IL-13 concentrations, goblet cell hyperplasia, and increased airway hyperresponsiveness. IL-25 has been reported to bind and signal through IL-17RB (IL-17BR, IL-17Rh1). It has been demonstrated recently that IL-17A signals through a heteromeric receptor composed of IL-17RA and IL-17RC. We sought to determine whether other IL-17 family ligands also utilize heteromeric receptor complexes. The required receptor subunits for IL-25 biological activities were investigated in vitro and in vivo using a combination of knockout (KO) mice and antagonistic Abs. Unlike wild-type mice, cultured splenocytes from either IL-17RB KO or IL-17RA KO mice did not produce IL-5 or IL-13 in response to IL-25 stimulation, and both IL-17RB KO and IL-17RA KO mice did not respond to intranasal administration of IL-25. Furthermore, treatment with antagonistic mAbs to either IL-17RB or IL-17RA completely blocked IL-25-induced pulmonary inflammation and airway hyperresponsiveness in naive BALB/c mice, similar to the effects of an antagonistic Ab to IL-25. Finally, a blocking Ab to human IL-17RA prevented IL-25 activity in a primary human cell-based assay. These data demonstrate for the first time that IL-25-mediated activities require both IL-17RB and IL-17RA and provide another example of an IL-17 family ligand that utilizes a heteromeric receptor complex.
•Fe-1.7C-11.3Cr-1.9Ni-1.2Mo roller steel is tested to a thermal fatigue.•Surface layer degradation is characterised for various fatigue conditions.•Microstructure prior and after thermal fatigue is ...characterised.•Quantitative assessment of thermal fatigue resistance of roller steel is presented.
Thermal fatigue resistance of a high Cr hot work roller steel is evaluated at 500, 600 and 700 °C. Surface layer degradation was investigated and characterised after a finite number of thermal cycles. Degradation mechanisms of the cooled surface layer in relation to the size, shape, orientation, distribution of carbides and crack oxidation progress were elucidated. Complex phenomena of crack growth is discussed where internal cracks nucleate due to stress at crack tip and oxidation along carbides follows from crack tail. Quantitative evaluation of cracks shows increased crack length with increasing temperature and number of thermal cycles.
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