Developmental Regulation of Lck Targeting to the CD8 Coreceptor Controls Signaling in Naive and Memory T Cells

The question of whether enhanced memory T cell responses are simply due to an increased frequency of specific cells or also to an improved response at the single cell level is widely debated. In this study, we analyzed T cell receptor (TCR) transgenic memory T cells and bona fide memory T cells isolated from virally infected normal mice using the tetramer technology. We found that memory T cells are qualitatively different from naive T cells due to a developmentally regulated rearrangement of the topology of the signaling machinery. In naive cytotoxic T cells, only a few CD8 molecules are associated with Lck and the kinase is homogeneously distributed inside the cell. However, in vivo priming of naive T cells induces the targeting of Lck to the CD8 coreceptor in the cell membrane and the consequent organization of a more efficient TCR signaling machinery in effector and memory cells

CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue

CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R-/-) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R-/- mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue

Field Measurements and Analysis on Temperature, Relative Humidity, Airflow Rate and Oil Fume Emission Concentration in a Typical Campus Canteen Kitchen in Tianjin, China

This study investigated the annual variation of the indoor thermal environment in a typical canteen kitchen and tried to evaluate the actual working status of the exhaust fume system. Parameters were measured in the canteen kitchen, including indoor environment (temperature, humidity, air velocity); outdoor environment (temperature; humidity); exhaust fume system (temperature, airflow rate, oil fume concentration, energy consumption), and makeup air system (temperature, humidity, air velocity) from April 2019 to January 2020. In addition, we also interviewed the chef’s thermal comfort in this kitchen. From the data available, we could find that 82.92% of the working hours in summer were above the acceptable range. Only 17.08% of the working hours were within the tolerance range (26–32 °C). The questionnaire results showed that 83.33% of chefs felt hot in summer. Most chefs’ wet sensations in the four seasons were neutral, and 91.6% of the chefs felt dissatisfied with the draft sensation. In addition, 88.33% of the chefs felt the fume overflowing from the exhaust hood. This may be because the exhaust fume system of the canteen kitchen was operated under the air velocity of 9.18 ± 1.6 m/s, and its exhaust airflow rate was 10,634.80 ± 189.30 m3/h, which is lower than the minimum exhaust airflow rate (12,312 m3/h). The measurement results indicated that the exhaust fume system could not remove the waste heat and fume pollutants effectively

Simulation Study of the Capture and Purification Performance of Exhaust Fume Systems in Chinese Commercial Kitchens—Case Study in Tianjin

A Chinese commercial kitchen fume exhaust (CCKEF) system mainly consists of a wall-mounted canopy hood, air duct and terminal electrostatic purifiers, the capture and purification performance of which should be guaranteed to obtain satisfactory indoor and outdoor air environment in engineering applications. However, few studies have focused on the operation performance of CCKEF systems. This study was aimed at providing a simulation method to investigate the operation performance of such systems. The simulation model of a representative CCKEF system was established using CFD software and validated with measured temperature, air velocity and purification efficiency with a deviation within 10%. The validated model was used to predict the indoor air environment and purification efficiency of the CCKEF system under different working conditions. The results showed that the temperature of transfer air from adjacent rooms had a greater impact on the thermal environment of the cooking area than the surface temperature of stoves. The exhaust air volume had a significant influence on both the indoor air environment and purification efficiency. CCKEF system was suggested to be operated at the optimum airflow according to the simultaneous coefficient of stoves as the energy consumption of the system can be saved by 3.75%

An Accurate and Convenient Method of Vehicle Spatiotemporal Distribution Recognition Based on Computer Vision

The Convenient and accurate identification of the traffic load of passing vehicles is of great significance to bridge health monitoring. The existing identification approaches often require prior environment knowledge to determine the location of the vehicle load, i.e., prior information of the road, which is inconvenient in practice and therefore limits its application. Moreover, camera disturbance usually reduces the measurement accuracy in case of long-term monitoring. In this study, a novel approach to identify the spatiotemporal information of passing vehicles is proposed based on computer vision. The position relationship between the camera and the passing vehicle is established, and then the location of the passing vehicle can be calculated by setting the camera shooting point as the origin. Since the angle information of the camera is pre-determined, the identification result is robust to camera disturbance. Lab-scale test and field measurement have been conducted to validate the reliability and accuracy of the proposed method

Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis

Abstract Background Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. Methods In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects. Results Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10–6, β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10–3, β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P < 0.001). Gene Ontology (GO) and KEGG pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function. Conclusions Our results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS

A Genomewide Integrative Analysis of GWAS and eQTLs Data Identifies Multiple Genes and Gene Sets Associated with Obesity

To identify novel susceptibility genes and gene sets for obesity, we conducted a genomewide expression association analysis of obesity via integrating genomewide association study (GWAS) and expression quantitative trait loci (eQTLs) data. GWAS summary data of body mass index (BMI) and waist-to-hip ratio (WHR) was driven from a published study, totally involving 339,224 individuals. The eQTLs dataset (containing 927,753 eQTLs) was obtained from eQTLs meta-analysis of 5,311 subjects. Integrative analysis of GWAS and eQTLs data was conducted by SMR software. The SMR single gene analysis results were further subjected to gene set enrichment analysis (GSEA) for identifying obesity associated gene sets. A total of 13,311 annotated gene sets were analyzed in this study. SMR single gene analysis identified 20 BMI associated genes (TUFM, SPI1, APOB48R, etc.). Also 3 WHR associated genes were detected (CPEB4, WARS2, and L3MBTL3). The significant association between Chr16p11 and BMI was observed by GSEA (FDR adjusted p value = 0.040). The TGCTGCT, MIR-15A, MIR-16, MIR-15B, MIR-195, MIR-424, and MIR-497 (FDR adjusted p value = 0.049) gene set appeared to be linked with WHR. Our results provide novel clues for the genetic mechanism studies of obesity. This study also illustrated the good performance of SMR for susceptibility gene mapping

Integrating Genome-Wide Association and eQTLs Studies Identifies the Genes and Gene Sets Associated with Diabetes

Aim. To identify novel candidate genes and gene sets for diabetes. Methods. We performed an integrative analysis of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) data for diabetes. Summary data was driven from a large-scale GWAS of diabetes, totally involving 58,070 individuals. eQTLs dataset included 923,021 cis-eQTL for 14,329 genes and 4,732 trans-eQTL for 2,612 genes. Integrative analysis of GWAS and eQTLs data was conducted by summary data-based Mendelian randomization (SMR). To identify the gene sets associated with diabetes, the SMR single gene analysis results were further subjected to gene set enrichment analysis (GSEA). A total of 13,311 annotated gene sets were analyzed in this study. Results. SMR analysis identified 6 genes significantly associated with fasting glucose, such as C11ORF10 (p value = 6.04 × 10−8), MRPL33 (p value = 1.24 × 10−7), and FADS1 (p value = 2.39 × 10−7). Gene set analysis identified HUANG_FOXA2_TARGETS_UP (false discovery rate = 0.047) associated with fasting glucose. Conclusion. Our study provides novel clues for clarifying the genetic mechanism of diabetes. This study also illustrated the good performance of SMR approach and extended it to gene set association analysis for complex diseases

Integrating genome-wide DNA methylation and mRNA expression profiles identified different molecular features between Kashin-Beck disease and primary osteoarthritis

Abstract Background Kashin-Beck disease (KBD) is an endemic osteochondropathy of unknown etiology. Osteoarthritis (OA) is a form of degenerative joint disease sharing similar clinical manifestations and pathological changes to articular cartilage with KBD. Methods A genome-wide DNA methylation profile of articular cartilage from five KBD patients and five OA patients was first performed using the Illumina Infinium HumanMethylation450 BeadChip. Together with a previous gene expression profiling dataset comparing KBD cartilage with OA cartilage, an integrative pathway enrichment analysis of the genome-wide DNA methylation and the mRNA expression profiles conducted in articular cartilage was performed by InCroMAP software. Results We identified 241 common genes altered in both the DNA methylation profile and the mRNA expression profile of articular cartilage of KBD versus OA, including CHST13 (NM_152889, fold-change = 0.5979, P methy = 0.0430), TGFBR1 (NM_004612, fold-change = 2.077, P methy = 0.0430), TGFBR2 (NM_001024847, fold-change = 1.543, P methy = 0.037), TGFBR3 (NM_001276, fold-change = 0.4515, P methy = 6.04 × 10−4), and ADAM12 (NM_021641, fold-change = 1.9768, P methy = 0.0178). Integrative pathway enrichment analysis identified 19 significant KEGG pathways, including mTOR signaling (P = 0.0301), glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate (P = 0.0391), glycosaminoglycan biosynthesis-keratan sulfate (P = 0.0278), and PI3K-Akt signaling (P = 0.0243). Conclusion This study identified different molecular features between Kashin-Beck disease and primary osteoarthritis and provided novel clues for clarifying the pathogenetic differences between KBD and OA

Additional file 3: Table S1. of Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis

Presenting significantly differentially methylated CpG sites between AS patients and healthy controls. (XLSX 167 kb