IL-17A Expression Is Localised to Both Mononuclear and Polymorphonuclear Synovial Cell Infiltrates

This study examines the expression of IL-17A-secreting cells within the inflamed synovium and the relationship to in vivo joint hypoxia measurements.IL-17A expression was quantified in synovial tissue (ST), serum and synovial fluid (SF) by immunohistochemistry and MSD-plex assays. IL-6 SF and serum levels were measured by MSD-plex assays. Dual immunofluorescence for IL-17A was quantified in ST CD15+ cells (neutrophils), Tryptase+ (mast cells) and CD4+ (T cells). Synovial tissue oxygen (tpO(2)) levels were measured under direct visualisation at arthroscopy. Synovial infiltration was assessed using immunohistochemistry for cell specific markers. Peripheral blood mononuclear and polymorphonuclear cells were isolated and exposed to normoxic or 3% hypoxic conditions. IL-17A and IL-6 were quantified as above in culture supernatants.IL-17A expression was localised to mononuclear and polymorphonuclear (PMN) cells in inflamed ST. Dual immunoflourescent staining co-localised IL-17A expression with CD15+ neutrophils Tryptase+ mast cells and CD4+T cells. % IL-17A positivity was highest on CD15+ neutrophils, followed by mast cells and then CD4+T-cells. The number of IL-17A-secreting PMN cells significantly correlated with sublining CD68 expression (r = 0.618, p<0.01). IL-17A SF levels correlated with IL-6 SF levels (r = 0.675, p<0.01). Patients categorized according to tp0(2)< or >20 mmHg, showed those with low tp0(2)<20 mmHg had significantly higher IL-17A+ mononuclear cells with no difference observed for PMNs. Exposure of mononuclear and polymorphonuclear cells to 3% hypoxia, significantly induced IL-6 in mononuclear cells, but had no effect on IL-17A expression in mononuclear and polymorphonuclear cells.This study demonstrates IL-17A expression is localised to several immune cell subtypes within the inflamed synovial tissue, further supporting the concept that IL-17A is a key mediator in inflammatory arthritis. The association of hypoxia with Il-17A expression appears to be indirect, probably through hypoxia-induced pro-inflammatory pathways and leukocyte influx within the joint microenvironment

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Effects of experimental warming on soil microbial communities in two contrasting subalpine forest ecosystems, eastern Tibetan Plateau, China

Soil microbial communities are primarily regulated by environmental temperature. Our study investigated the effects of global warming on soil microbial community composition as measured via phospholipid fatty acid (PLFA) analysis and soil chemical characteristics in relation to soil depth in a dragon spruce plantation and a spruce-fir-dominated natural forestin the Eastern Tibetan Plateau. Open-top chambers were utilized to increase the soil and air temperature. Soil samples were collected from the 0-10 cm, 10-20 cm, and 20-30 cm layers after a 4-year warming. Our results showed that the soil microbial community and the contents of TC (Total carbon), TN (Total nitrogen), NO (3) (-) , and NH (4) (+) responded differently to warming in the two contrasting forests, especially at the 0-10 cm soil depth. Warming increased soil microbial biomass at the 0-20 cm depth of soil in natural forest but reduced it at the 0-10 cm depth ofsoil in the plantation. In contrast, the TC and TN contents were reduced in most soil layers of a natural forest but increased in all of the soil layers of the plantation under warming conditions. This result suggested that the effects of warming on soil microbial community and soil C and N pools would differ according to soil depth and forest types; thus, the two contrasting forests would under go differing changes following the future climate warming in this region

Molecular Simulation of 3D Turbulent Channel Flow

The diffusive information preservation (D-IP) method is utilized to simulate three-dimensional turbulent channel flow. The Knudsen number and Reynolds number based on the channel half-width and mean velocity are 5 square 10(square 5) and 2800, respectively. The averaged velocity profile and the higher order turbulent statistics obtained by D-IP agree well with the DNS results given by Kim, Moin and Moser. Turbulent mixing length and turbulent viscosity obtained by the present results based on kinetic analogy are found to be comparable with the classic theory of Prandl's mixing length and Boussinesq eddy viscosity

Analysis of transport properties determined by Langevin dynamics using Green-Kubo formulae

Recently, the Langevin dynamics method has been applied to simulate gas flows. It is very crucial to evaluate whether the Langevin dynamics could correctly predict transport properties of gas or not. In this paper, the transport properties of Langevin velocity model and acceleration model are analyzed by using Green-Kubo formulae. For the Langevin velocity model, the time correlation functions have the exact exponent forms, and the Prandtl number for monatomic gas is predicted to be 3/2. For the Langevin acceleration model with an additional time scale, the molecular movements change from Markovian process to Non-Markovian process, and the Prandtl number could be adjusted to some extent. In the limit of equilibrium, there is a minimum about 1.298 for the Prandtl number of monatomic gas when the two time scales are equal in Langevin acceleration model. Besides theoretical analyses, molecular simulations according to the Langevin velocity model and acceleration model are performed, and the simulation results validate our analytical solutions. (C) 2014 Elsevier B.V. All rights reserved

Modeling of dynamic crack branching by enhanced extended finite element method

The conventional extended finite element method (XFEM) is enhanced in this paper to simulate dynamic crack branching, which is a top challenge issue in fracture mechanics and finite element method. XFEM uses the enriched shape functions with special characteristics to represent the discontinuity in computation field. In order to describe branched cracks, it is necessary to set up the additional enrichment. Here we have developed two kinds of branched elements, namely the &quot;element crossed by two separated cracks&quot; and &quot;element embedded by a junction&quot;. Another series of enriched degrees of freedom are introduced to seize the additional discontinuity in the elements. A shifted enrichment scheme is used to avoid the treatment of blending element. Correspondingly a new mass lumping method is developed for the branched elements based on the kinetic conservation. The derivation of the mass matrix of a four-node quadrilateral element which contains two strong discontinuities is specially presented. Then by choosing crack speed as the branching criterion, the branching process of a single mode I crack is simulated. The results including the branching angle and propagation routes are compared with that obtained by the conventionally used element deletion method

A Comprehensive Study of the Electrostatic Discharge Sensitivity and Chargeability of Tris(carbohydrazide)zinc Perchlorate

Most primary explosives are non-conductors, easily accumulate charge when contacting with and separating from other materials, and are sensitive to electrostatic discharge (ESD). In order to reduce the number of accidents caused by ESD initiation of primary explosives, studies on their electrostatic hazards are necessary. This work presents comprehensive experimental results of electrostatic discharge sensitivity and chargeability of tris(carbohydrazide)zinc perchlorate (ZnCP) under different conditions. The influences of the testing conditions, of devices, particle size, ambient temperature and relative humidity on the electrostatic discharge sensitivity and chargeability have been investigated in detail, and the quantitative regression equations obtained

Responses of nutrient capture and fine root morphology of subalpine coniferous tree Picea asperata to nutrient heterogeneity and competition

Investigating the responses of trees to the heterogeneous distribution of nutrients in soil and simultaneous presence of neighboring roots could strengthen the understanding of an influential mechanism on tree growth and provide a scientific basis for forest management. Here, we conducted two split-pot experiments to investigate the effects of nutrient heterogeneity and intraspecific competition on the fine root morphology and nutrient capture of Picea asperata. The results showed that P. asperata efficiently captured nutrients by increasing the specific root length (SRL) and specific root area (SRA) of first-and second-order roots and decreasing the tissue density of first-order roots to avoid competition for resources and space with neighboring roots. The nutrient heterogeneity and addition of fertilization did not affect the fine root morphology, but enhanced the P and K concentrations in the fine roots in the absence of a competitor. On the interaction between nutrient heterogeneity and competition, competition decreased the SRL and SRA but enhanced the capture of K under heterogeneous soil compared with under homogeneous soil. Additionally, the P concentration, but not the K concentration, was linearly correlated to root morphology in heterogeneous soil, even when competition was present. The results suggested that root morphological features were only stimulated when the soil nutrients were insufficient for plant growth and the nutrients accumulations by root were mainly affected by the soil nutrients more than the root morphology

Whole-exome Sequencing Analysis Identifies Mutations in the EYS Gene in Retinitis Pigmentosa in the Indian Population

Retinitis pigmentosa (RP) is a rare heterogeneous genetic retinal dystrophy disease, and despite years of research, known genetic mutations can explain only approximately 60% of RP cases. We sought to identify the underlying genetic mutations in a cohort of fourteen Indian autosomal recessive retinitis pigmentosa (arRP) families and 100 Indian sporadic RP cases. Whole-exome sequencing (WES) was performed on the probands of the arRP families and sporadic RP patients, and direct Sanger sequencing was used to confirm the causal mutations identified by WES. We found that the mutations of EYS are likely pathogenic mutations in two arRP families and eight sporadic patients. Specifically, we found a novel pair of compound heterozygous mutations and a novel homozygous mutation in two separate arRP families, and found two novel heterozygous mutations in two sporadic RP patients, whereas we found six novel homozygous mutations in six sporadic RP patients. Of these, one was a frameshift mutation, two were stop-gain mutations, one was a splicing mutation, and the others were missense mutations. In conclusion, our findings expand the spectrum of EYS mutations in RP in the Indian population and provide further support for the role of EYS in the pathogenesis and clinical diagnosis of RP