Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset of the variations causing susceptibility to systemic lupus erythematosus (SLE). Two independent disease association signals in the HLA-D region identified two regulatory regions containing 3562 polymorphisms that modified thirty-seven transcription factor binding sites. These extensive functional variations are a new and potent facet of HLA polymorphism. Variations modifying the consensus binding motifs of IRF4 and CTCF in the XL9 regulatory complex modified the transcription of HLA-DRB1, HLA-DQA1 and HLA-DQB1 in a chromosome-specific manner, resulting in a 2.5-fold increase in the surface expression of HLA-DR and DQ molecules on dendritic cells with SLE risk genotypes, which increases to over 4-fold after stimulation. Similar analyses of fifteen other SLE risk loci identified 1206 functional variants tightly linked with disease-associated SNPs and demonstrated that common disease alleles contain multiple causal variants modulating multiple immune system genes.DOI: http://dx.doi.org/10.7554/eLife.12089.001

To explore the effects of different types of forest environments for forest therapy, this study focused on forest resting environments. Seven representative forest resting environments found in field research in Beijing were used as independent variables and were shown to subjects by a virtual reality (VR) video. Stress level was used as the dependent variable, and blood pressure, heart rate, salivary amylase, and the Brief Profile of Mood States (BPOMS) were used as physiological and psychological indicators. A between-subjects design was used in the experiment. A total of 96 subjects were randomly assigned to each environment type, and only one type of forest resting environment was observed. Through the relevant sample t-test and one-way analysis of variance, the pre- and post-test data of the indicators were analyzed. This study found that all the seven different types of forest resting environments can produce stress relief effects to some extent. Different types of forest resting environments have different effects on relieving stress. The most natural environment does not have the most significant effect on stress relief. A water landscape has a positive effect on the relief of stress. The conclusions of this study are conducive to the better use of the forest environment for forest therapy services.

According to the Method of Moment, a new method to analyze the grid fed by harmonic currents is presented. The method can be used to the condition that the grid is in at least ten-layer soil with a frequency of the injected currents up to 1 MHz. There can be more than one injected current, and the grounding conductor of the grid can be put in any form. Validation of the method is presented by comparing it with other existing methods. As an application of the presented method, breaks in the substation's grounding grid are diagnosed by the measured voltages on the surface of the ground.

It has been proposed that immune injury is the central mechanism of pathogenesis of the infectious disease, severe acute respiratory syndrome (SARS). To gain a better understanding of immune injury in the spleen, we investigated the number and distribution of various immune cell types in the spleens of SARS patients. We performed autopsies on six confirmed SARS cases, with six normal subjects as controls; spleen samples from these autopsies were examined with hematoxylin and eosin (H&E) sections, in situ hybridization for SARS virus genomic sequences, and immunohistochemistry with seven monoclonal antibodies to five cell types. The number and distribution of these cells were measured and analyzed using an image analysis system. SARS genomic sequences were detected in all SARS spleens. The SARS spleens all had severe damage to the white pulp and showed an alteration of the normal distribution of various cell types. Immunocytes in the red pulp were decreased by 68.0-90.7% except for CD68+ macrophages and human leukocyte antigen (HLA)-DR positive antigen-presenting cells (APC), which were decreased to a lesser degree. On average, CD68+ macrophages were increased in size by 2.21-fold. We hypothesize that the collapse of the splenic immune system plays a key role in the clinical outcome of these patients.

Tuberculosis (TB) is a severe infectious disease that seriously endangers human health. The immune defence mechanism of the body against TB is still unclear. The purpose of this study was to find the key molecules involved in the immune defence response during TB infection, and provide reference for the treatment of TB and further understanding of the immune defence mechanism of the body. Data from http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83456 were downloaded from GEO data sets for analysis, and a total of 192 differentially expressed genes were screened out. Most of these genes are enriched in the interferon signalling pathway and are defence response–related. We also found that STAT1 plays an important role in the immune defence of TB infection and it is one of the key genes related to interferon signalling pathway. STAT1‐related molecules including hsa‐miR‐448, hsa‐miR‐223‐3p, SAMD8_hsa_circRNA 994 and TWF1_hsa_circRNA 9897 were therefore screened out. Furthermore, expression levels of hsa‐miR‐448 and hsa‐miR‐223‐3p were then verified by qRT‐PCR. Results showed that both hsa‐miR‐448 and hsa‐miR‐223‐3p were down‐regulated in plasma from patients with pulmonary TB. Taken together, our data indicate that an mRNA‐miRNA‐circRNA interaction chain may play an important role in the infection of MTB, and STAT1 and related molecules including hsa‐miR‐223‐3p, has‐miR‐448, SAMD8_hsa_circRNA994 and TWF1_hsa_circRNA9897 were identified as potential biomarkers in the development of active TB.

In a high soil resistivity area, counterpoise wires are applied to decrease the grounding resistance of tower grounding devices. If the conductor of counterpoise wire is very long, although the power frequency grounding resistance of the tower grounding device is decreased, the lightning protection performance of the transmission line is still not good. The influences of the length of grounding electrodes on the lightning transient characteristic were analyzed. The dynamic and nonlinear effect of soil ionization around the grounding electrode was considered in the analysis model of transient characteristics for the grounding electrodes under lightning impulse. The counterpoise wire has an effective length when lightning passes through it. When the length of a grounding electrode exceeds the effective length, the grounding conductor will not be utilized effectively. The simulating experiments were performed to analyze influences of the length of the counterpoise wire on the impulse characteristics. The formulae to calculate the impulse effective lengths of counterpoise wires were proposed. The model proposed in the paper has been validated by comparing the numerical results with experimental tests.

Background: Acne vulgaris is a common inflammatory skin disease, affecting adolescents across the globe. Recent evidences underline that Propionibacterium acnes (P. acnes) promotes acne through Toll-like receptor (TLR) activation. Especially, Toll-like receptor 2 (TLR2) has emerged as one of the major classes of pattern recognition receptors (PRRs) that are recognizing P. acnes in the epidermis and responsible for inflammation. Conclusions: Although P. acnes has been known to be one of the major causes of acne vulgaris, an appropriate drug to alleviate acne pathogenesis is poorly developed. This review focuses on the molecular structure of TLR2 as well as mechanism how TLR2 recognize P. acnes to induce inflammatory cytokines, which is related to acne vulgaris pathogenesis. Rigorous study about P. acnes mediated by TLR2 activation may provide insight into novel therapeutic targets of acne vulgaris.

Probiotics might offer an attractive alternative to prevent and control Clostridium difficile (C. difficile) infection (CDI). Limited information is available on the ability of commercially used bifidobacterial strains to inhibit C. difficile. This study examined the anti-clostridial effects of Bifidobacterium longum JDM301, a widely used commercial probiotic strain in China, in vitro and in vivo. In vitro evaluation revealed a significant reduction in C. difficile counts when JDM301 was co-cultured with C. difficile, which was correlated with the significant decrease in clostridial toxin titres (TcdA and TcdB). Furthermore, the cell-free culture supernatants (CFS) of JDM301 inhibited C. difficile growth and degraded TcdA and TcdB. Notably, the results showed that acid pH promoted the degradation of TcdA by CFS from JDM301. Furthermore, comparative studies among 10 B. longum strains were performed, which showed that the inhibitory effect of CFS from JDM301 was similar with the other 8 B. longum strains and higher than strain BLY1. However, when it was neutralized, the significant different was lost. When present together, it was suggested that the acid pH induced by probiotics not only played important roles in the growth inhibition against C. difficile resulting in the reduction of toxins titres, but also directly promoted the degradation of clostridial toxin. In vivo studies proved that JDM301 partially relieved damage to tissues caused by C. difficile and also decreased the number of C. difficile and toxin levels. In summary, our results demonstrated that the commercial strain, JDM301 could be considered a probiotic able to exert anti-toxin capability and most of the CFS from Bifidobacterium were able to inhibit the growth of C. difficile, depending on acid pH. These results highlighted a potential that JDM301 could be helpful in preventing CDI and that most of the bifidobacterial strains could (at least partially) exert protective effects by reducing toxin titres through growth inhibition against toxigenic C. difficile.