Summary
Background
Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD ...are unknown.
Objective
We investigated whether and how S. aureus‐derived membrane vesicles (MVs) contribute to worsening of AD.
Methods
Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions. HaCaT cells were treated with S. aureus MVs and were analysed for the expression of cytokine genes. Immunopathology and cytokine gene profiles were analysed after topical application of S. aureus MVs to AD‐like skin lesions in a mouse model.
Results
The MV component SPA was detected in the keratinocytes as well as in the intercellular space of the epidermis of AD lesions colonized with S. aureus. Intact MVs from S. aureus delivered their components to keratinocytes and stimulated pro‐inflammatory cytokine gene expression in vitro. A knock‐down of Toll‐like receptor 2 or nucleotide‐binding oligomerization domain 2 using small interfering RNAs suppressed interleukin‐8 gene expression. Topical application of intact S. aureus MVs to AD‐like skin lesions in the mouse model induced massive infiltration of inflammatory cells and the resulting eczematous dermatitis. This inflammatory reaction was associated with a mixed Th1/Th2 immune response and enhanced expression of chemokine genes in AD‐like skin lesions.
Conclusions and Clinical Relevance
This study showed the importance of S. aureus MVs as a potent mediator for worsening of AD among many exogenous worsening factors of AD. Thus, S. aureus MVs may be regarded as one of the therapeutic targets for the management of AD aggravation.
Aims/hypothesis
Obesity and insulin resistance are associated with low-grade chronic inflammation. Glucagon-like peptide-1 (GLP-1) is known to reduce insulin resistance. We investigated whether GLP-1 ...has anti-inflammatory effects on adipose tissue, including adipocytes and adipose tissue macrophages (ATM).
Methods
We administered a recombinant adenovirus (rAd) producing GLP-1 (rAd-GLP-1) to an
ob/ob
mouse model of diabetes. We examined insulin sensitivity, body fat mass, the infiltration of ATM and metabolic profiles. We analysed the mRNA expression of inflammatory cytokines, lipogenic genes, and M1 and M2 macrophage-specific genes in adipose tissue by real-time quantitative PCR. We also examined the activation of nuclear factor κB (NF-κB), extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase (JNK) in vivo and in vitro.
Results
Fat mass, adipocyte size and mRNA expression of lipogenic genes were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Macrophage populations (F4/80
+
and F4/80
+
CD11b
+
CD11c
+
cells), as well as the expression and production of IL-6, TNF-α and monocyte chemoattractant protein-1, were significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Expression of M1-specific mRNAs was significantly reduced, but that of M2-specific mRNAs was unchanged in rAd-GLP-1-treated
ob/ob
mice. NF-κB and JNK activation was significantly reduced in adipose tissue of rAd-GLP-1-treated
ob/ob
mice. Lipopolysaccharide-induced inflammation was reduced by the GLP-1 receptor agonist, exendin-4, in 3T3-L1 adipocytes and ATM.
Conclusions/interpretation
We suggest that GLP-1 reduces macrophage infiltration and directly inhibits inflammatory pathways in adipocytes and ATM, possibly contributing to the improvement of insulin sensitivity.
Rapid industrialization and urbanization in developing countries has led to an increase in air pollution, along a similar trajectory to that previously experienced by the developed nations. In China, ...particulate pollution is a serious environmental problem that is influencing air quality, regional and global climates, and human health. In response to the extremely severe and persistent haze pollution experienced by about 800 million people during the first quarter of 2013 (refs 4, 5), the Chinese State Council announced its aim to reduce concentrations of PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 micrometres) by up to 25 per cent relative to 2012 levels by 2017 (ref. 6). Such efforts however require elucidation of the factors governing the abundance and composition of PM2.5, which remain poorly constrained in China. Here we combine a comprehensive set of novel and state-of-the-art offline analytical approaches and statistical techniques to investigate the chemical nature and sources of particulate matter at urban locations in Beijing, Shanghai, Guangzhou and Xi'an during January 2013. We find that the severe haze pollution event was driven to a large extent by secondary aerosol formation, which contributed 30-77 per cent and 44-71 per cent (average for all four cities) of PM2.5 and of organic aerosol, respectively. On average, the contribution of secondary organic aerosol (SOA) and secondary inorganic aerosol (SIA) are found to be of similar importance (SOA/SIA ratios range from 0.6 to 1.4). Our results suggest that, in addition to mitigating primary particulate emissions, reducing the emissions of secondary aerosol precursors from, for example, fossil fuel combustion and biomass burning is likely to be important for controlling China's PM2.5 levels and for reducing the environmental, economic and health impacts resulting from particulate pollution.
Here, we add the resonant γp → N*c¯c → J/ψp amplitudes to examine the effects of N*c¯c excitations on the cross sections of γp→J/ψp in the near threshold energy region covered by the recent ...experiments at Jefferson Lab. The N*c¯c → MB transition matrix elements are determined from the partial decay widths predicted by the considered meson-baryon coupled-channel models of N*c¯c.
Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) ...is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required.
Traditional multiobjective evolutionary algorithms (MOEAs) consider multiple objectives as a whole when solving multiobjective optimization problems (MOPs). However, this consideration may cause ...difficulty to assign fitness to individuals because different objectives often conflict with each other. In order to avoid this difficulty, this paper proposes a novel coevolutionary technique named multiple populations for multiple objectives (MPMO) when developing MOEAs. The novelty of MPMO is that it provides a simple and straightforward way to solve MOPs by letting each population correspond with only one objective. This way, the fitness assignment problem can be addressed because the individuals' fitness in each population can be assigned by the corresponding objective. MPMO is a general technique that each population can use existing optimization algorithms. In this paper, particle swarm optimization (PSO) is adopted for each population, and coevolutionary multiswarm PSO (CMPSO) is developed based on the MPMO technique. Furthermore, CMPSO is novel and effective by using an external shared archive for different populations to exchange search information and by using two novel designs to enhance the performance. One design is to modify the velocity update equation to use the search information found by different populations to approximate the whole Pareto front (PF) fast. The other design is to use an elitist learning strategy for the archive update to bring in diversity to avoid local PFs. CMPSO is comprehensively tested on different sets of benchmark problems with different characteristics and is compared with some state-of-the-art algorithms. The results show that CMPSO has superior performance in solving these different sets of MOPs.
Mobility-Aware Caching in D2D Networks Rui Wang; Jun Zhang; Song, S. H. ...
IEEE transactions on wireless communications,
2017-Aug., 2017-8-00, 20170801, Letnik:
16, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Caching at mobile devices can facilitate device-todevice (D2D) communications, which may significantly improve spectrum efficiency and alleviate the heavy burden on backhaul links. However, most ...previous works ignored user mobility, thus having limited practical applications. In this paper, we take advantage of the user mobility pattern by the inter-contact times between different users, and propose a mobility-aware caching placement strategy to maximize the data offloading ratio, which is defined as the percentage of the requested data that can be delivered via D2D links rather than through base stations. Given the NP-hard caching placement problem, we first propose an optimal dynamic programming algorithm to obtain a performance benchmark with much lower complexity than exhaustive search. We then prove that the problem falls in the category of monotone submodular maximization over a matroid constraint, and propose a time-efficient greedy algorithm, which achieves an approximation ratio as 2/1. Simulation results with real-life data sets will validate the effectiveness of our proposed mobility-aware caching placement strategy. We observe that users moving at either a very low or very high speed should cache the most popular files, while users moving at a medium speed should cache less popular files to avoid duplication.
Background
The interaction between light and the skin determine how the skin looks to the human eye. Light can be absorbed, scattered, and reflected by different components of the skin in a variety ...of different ways. Here, we focus on the scattering properties of the outmost layer, the stratum corneum (SC). However, we currently have limited methods with which to distinguish the scattering of light by SC from the changes due to other components of the skin.
Materials and methods
Dark‐field images of tape‐striped corneocytes were used in vitro to study the differences in light scattered by the SC and other skin components. Several optical clearing agents (OCAs) were tested for their ability to reduce light scattering. Physical properties of the SC (water content, keratin configuration, and volume) after OCA treatment were investigated using FT‐IR, confocal Raman microscopy, and 3D laser microscopy.
Results
Urea derivatives, several reducing sugars, and sugar alcohols, which were used as OCA in optics and also used as humectants in cosmetic area, could reduce scattering. However, unlike dehydration in optics, penetration of water into the keratin was increased at low OCA concentrations. In such conditions, the volume of corneocytes was increased but their stiffness was reduced.
Conclusion
By analyzing the tape‐striped SC, we were able to measure the changes in the optical and physical properties of corneocytes in response to OCAs. Hydration of the SC layer by OCAs reduces light scattering from the corneocytes and would be helpful in moisturizing the skin and helping the skin look healthy.
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