Orphan chemoattractant receptor GPR15 mediates dendritic epidermal T‐cell recruitment to the skin

Homing of murine dendritic epidermal T cells (DETCs) from the thymus to the skin is regulated by specific trafficking receptors during late embryogenesis. Once in the epidermis, Vγ3δ1 TCR DETCs are maintained through self‐renewal and participate in wound healing. GPR15 is an orphan G protein‐linked chemoattractant receptor involved in the recruitment of regulatory T cells to the colon. Here we show that GPR15 is highly expressed on fetal thymic DETC precursors and on recently recruited DETCs, and mediates the earliest seeding of the epidermis, which occurs at the time of establishment of skin barrier function. DETCs in GPR15^?/? mice remain low at birth, but later participation of CCR10 and CCR4 in DETC homing allows DETCs to reach near normal levels in adult skin. Our findings establish a role for GPR15 in skin lymphocyte homing and suggest that it may contribute to lymphocyte subset targeting to diverse epithelial sites.     

Epigenome‐wide DNA methylation changes with development of arsenic‐induced skin lesions in Bangladesh: A case–control follow‐up study

Studies have found an association between aberrant DNA methylation and arsenic‐induced skin lesions. However, little is known about DNA methylation changes over time in people who develop arsenic‐induced skin lesions. We sought to investigate epigenome‐wide changes of DNA methylation in people who developed arsenic‐induced skin lesions in a 10‐year period. In 2009–2011, we conducted a follow‐up study of 900 skin lesion cases and 900 controls and identified 10 people who developed skin lesions since a baseline survey in 2001–2003. The 10 cases (“New Cases”) were matched with 10 controls who did not have skin lesions at baseline or follow‐up (“Persistent Controls”). Drinking water and blood samples were collected, and skin lesion was diagnosed by the same physician at both time points. We measured DNA methylation in blood using Infinium HumanMethylation450K BeadChip, followed by quantitative validation using pyrosequencing. Two‐sample t‐tests were used to compare changes in percent methylation between New Cases and Persistent Controls. Six CpG (cytosine‐phosphate‐guanine) sites with greatest changes of DNA methylation over time among New Cases were further validated with a correlation of 93% using pyrosequencing. One of the validated CpG site (cg03333116; change of %methylation was 13.2 in New Cases versus ?0.09 in Persistent Controls; P < 0.001) belonged to the RHBDF1 gene, which was previously reported to be hypermethylated in arsenic‐exposed cases. We examined DNA methylation changes with the development of arsenic‐induced skin lesions over time but nothing was statistically significant given the small sample size of this exploratory study and the high dimensionality of data. Environ. Mol. Mutagen. 55:449–456, 2014. © 2014 Wiley Periodicals, Inc.     

Polymorphisms in the TNF‐α, TNFR1 gene and risk of rheumatoid arthritis in Chinese Han population

Recent advances have highlighted a major genetic contribution to the pathogenesis of rheumatoid arthritis (RA).The aim of this study was to investigate whether polymorphisms of TNF‐α (rs1800630, rs1800629) and TNFR1 (rs767455) were associated with susceptibility to and clinical outcome of RA in Chinese Han population. The target gene polymorphisms were genotyped in 256 patients with RA and 331 healthy controls using a high resolution melting (HRM) method. ESR, CRP, RF anti‐CCP and anti‐GPI level were also assayed and compared in genotypes of each polymorphism. Significant difference was observed in the genotype distributions and allele frequencies of TNF‐α rs1800629 (P = 0.001, P < 0.001, respectively) between patients with RA and controls. There is no evidence to suggest an association between genotypes of the 3 SNPs according to age, gender, disease duration, DAS28 and serum level of autoantibodies. This study identifies a potentially important role for TNF‐α rs1800629 polymorphisms in the susceptibility to RA.However, further studies in larger cohorts are required.     

The Impact of Chronic Kidney Disease on Lipid Management and Goal Attainment in Patients with Atherosclerosis Diseases in Taiwan

Background: Patients with chronic kidney disease (CKD) is a very high risk cardiovascular disease population and should be treated aggressively. We investigated lipid management in CKD patients with atherosclerosis in Taiwan.Methods: 3057 patients were enrolled in a multi-center study (T-SPARCLE). Lipid goal are defined as total cholesterol (TC) < 160mg/dl, low-density lipoprotein (LDL) <100 mg/dl, high-density lipoprotein (HDL) > 40 mg/dl in men, HDL > 50 mg/dl in women, non-HDL cholesterol < 130mg/dl, and triglyceride < 150 mg/dl.Results: Compared with those without CKD (n=2239), patients with CKD (n=818) had more co-morbidities (hypertension, glucose intolerance, stroke and heart failure) and lower HDL but higher triglyceride levels. Overall 2168 (70.5%) patients received lipid-lowering agents. There was similar equivalent statin potency between CKD and non-CKD groups. The goal attainment is lower in HDL and TG in the CKD group as compared with non-CKD subjects (47.1 vs. 51.9% and 63.2 vs. 68.9% respectively, both p < 0.02). Analysis of sex and CKD interaction on goals attainment showed female CKD subjects had lower non-HDL and TG goals attainment compared with non-CKD males (both p < 0.019).Conclusion: Although presenting with more comorbidities, the CKD population had suboptimal lipid goal attainment rate as compared with the non-CKD population. Further efforts may be required for better lipid control especially on the female CKD subjects.     

Role of Interleukin-22 in liver diseases

Introduction

Interleukin (IL)-22, originally referred to as IL-TIF for IL-10-related T cell-derived inducible factor, is a member of the IL-10-like cytokine family. IL-22 is highly expressed by Th17 cells and is tightly linked to chronic inflammation, including inflammatory bowel disease and local intestinal inflammation among others.

Materials and methods

A PubMed and Web of Science databases search was performed for studies providing evidences on the role of IL-22 in liver diseases.

Conclusion

IL-22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL-22 receptor 1 and IL-10 receptor 2. This review concisely summarizes the role of IL-22 in the development progression of liver disease of different etiologies. It is focused mainly on the IL-22 intracellular signaling and its influence on liver diseases.     

Interleukin-7 Receptor Single Nucleotide Polymorphism rs6897932 (C/T) and the Susceptibility to Systemic Lupus Erythematosus

Emerging evidences were accumulated to support the view that aberrant interleukin-7 (IL-7) signaling might be associated with autoimmunity. Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes. Given these, this study was conducted to investigate whether an association existed between SNP rs6897932 and the susceptibility to systemic lupus erythematosus (SLE), a severe systemic autoimmune disease. In this context, 816 SLE patients and 816 controls from a Chinese population were recruited for this study, and the results showed that the major allele C of rs6897932 showed a higher frequency in SLE patients compared with controls (P?=?0.039, C versus T); significant difference was also detected under a recessive model with regard to the distribution of genotype frequencies between SLE patients and controls (P?=?0.041, CC versus CT + TT), which was not consistent with the results under a dominant model (P?=?0.349, CC + CT versus TT). Moreover, association studies were also performed contraposing the relationship between the SNP rs6897932 C/T and lupus nephritis as well as 10 clinical features of SLE; however, no significant association signal was found regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of 11 sub-phenotypes. In conclusion, the major allele C of SNP rs6897932 may be associated with increased SLE risk in Chinese populations, and further studies are still encouraged to shed light on the true associations between SLE and its susceptibility genes with respect to IL-7R gene.     

Characterization of the biological properties and complete genome sequence analysis of a cattle-derived rabies virus isolate from the Guangxi province of southern China

In this study, a street rabies virus isolate, GXHXN, was obtained from the brain of one rabid cattle in Guangxi province of southern China. To characterize the biological properties of GXHXN, we first evaluated its pathogenicity using 4-week-old adult mice. GXHXN was highly pathogenic with a short incubation period and course of disease. Its LD₅₀ of 10^?6.86/mL is significantly higher than the LD₅₀ of 10^?5.19/mL of GXN119, a dog-derived rabies virus isolate. It also displayed a higher neurotropism index than the rRC-HL strain. However, the relative neurotropism index of GXHXN was slightly lower than that of GXN119. Analyzing antigenicity using anti-N and anti-G monoclonal antibodies (MAbs), all tested anti-N MAbs reacted similarly to GXHXN, CVS, and rRC-HL, but the reaction of anti-N MAbs to GXHXN was slightly different from GXN119. Moreover, 2/11 tested anti-G mAbs showed weaker reactivity to GXHXN than rRC-HL, whereas 4/11 showed stronger reactivity to GXHXN than CVS and GXN119, indicating that the structures of G might differ. In order to understand its genetic variation and evolution, the complete GXHXN genome sequence was determined and compared with the known 12 isolates from other mammals. A total of 42 nucleotide substitutions were found in the full-length genome, including 15 non-synonymous mutations. The G gene accounts for the highest nucleotide substitution rate of 0.70 % in ORF and an amino acid substitution rate of 0.95 %. Phylogenetic trees based on the complete genome sequence as well as the N and G gene sequences from 37 known rabies isolates from various mammals demonstrated that the GXHXN is closely related to the BJ2011E isolate from a horse in Beijing, the WH11 isolate from a donkey in Hubei, and isolates from dogs in the Fujian and Zhejiang provinces. These findings will be helpful in exploring the molecular mechanisms underlying interspecies transmission and the genetic variation of the rabies virus in different mammal species.     

医学院大学生自我控制能力对心理健康的影响

目的对医学院大学生的自我控制能力与心理健康水平及其关系进行调查,为大学生心理健康教育提供依据。方法采用张秋凌等人修订的自我控制问卷和症状自评量表对526名医学院本科生进行问卷调查。结果非医学专业大学生的自我控制总分显著高于医学专业大学生(t=-2.38,P0.05),不同年级大学生的自我控制总分有显著的组间差异(F=3.54,P0.01);冲动冒险性与自我情绪性维度在性别、层次、专业及年级等方面有显著差异;自我控制总分与症状自评量的强迫症状具有显著的负相关,与恐怖因子得分有显著的正相关(r=0.095,P0.05)。结论医学院大学生的自我控制能力具有专业差异和年级差异的特点,主要表现在冲动冒险控制和自我情绪的控制方面;自我控制能力对心理健康的影响主要表现在冲动冒险和自我情绪的控制对强迫和恐怖两个方面的影响。     

Time‐dependent effects of isoflurane and dexmedetomidine on functional connectivity,spectral characteristics,and spatial distribution of spontaneous BOLD fluctuations

Anesthesia is often necessary to perform fMRI experiments in the rodent model; however, commonly used anesthetic protocols may manifest changing brain conditions over the duration of the study. This possibility was explored in the current work. Eleven rats were anesthetized with 2% isoflurane anesthesia; four rats were anesthetized for a short period (30 min, simulating induction and fMRI setup) and seven rats were anesthetized for a long period (3 h, simulating surgical preparation). Following the initial anesthetic period, isoflurane was discontinued, and a dexmedetomidine bolus (0.025 mg/kg) and continuous subcutaneous infusion (0.05 mg/kg/h) were administered. Blood‐oxygen‐level dependent resting state imaging was performed every 30 min from 0.75 h post dexmedetomidine bolus until 5.75 h post‐bolus. Evaluation of power spectra obtained from time courses in the primary somatosensory cortex revealed, in general, a monotonic increase in low‐frequency power (0.05–0.3 Hz) in both groups over the duration of resting state imaging. Greater low‐band spectral power (0.05–0.15 Hz) is present in the short isoflurane group for the first 2.75 h, but the spectra become highly uniform at 3.25 h. The emergence of a ~0.18 Hz peak, beginning at the 3.75 h time point, exists in both groups and evolves similarly, increasing in strength as the duration of dexmedetomidine sedation (and time since isoflurane cessation) extends. In the long isoflurane group only, bilateral functional connectivity strengthens with anesthetic duration, and correlation is linearly linked to low‐band spectral power. Convergence of connectivity and spectral metrics between the short and long isoflurane groups occurs at ~3.25 h, suggesting the effects of isoflurane have subsided. Researchers using dexmedetomidine following isoflurane for functional studies should be aware of the duration specific effects of the pre‐scan isoflurane durations as well as the continuing influences of long‐term imaging under dexmedetomidine. Copyright © 2014 John Wiley & Sons, Ltd.     

Three Isothermal Amplification Techniques for Rapid Identification of Cladophialophora carrionii,an Agent of Human Chromoblastomycosis

In this study, we developed rapid and sensitive assays for the detection of Cladophialophora carrionii, a common agent of human chromoblastomycosis. The isothermal techniques evaluated were rolling-circle amplification (RCA), multiplex ligation-dependent probe amplification (MLPA), and loop-mediated isothermal amplification (LAMP). The probes for RCA and MLPA were designed with target sequences in the rDNA internal transcribed spacer gene (ITS) region, and LAMP primers were designed using the elongation factor 1α gene (EF1); these probes and primers specifically amplified DNA of isolates of the species. The three techniques were sufficiently specific and sensitive for discriminating target DNA of C. carrionii from that of related Cladophialophora species and other agents of chromoblastomycosis. RCA, MLPA, and LAMP are advantageous in their reliability and ease of operation compared to standard PCR and conventional methods.