13 research outputs found

    Single-cell transcriptomics reveals peripheral immune responses in non-segmental vitiligo

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    BackgroundVitiligo is a common autoimmune depigmented dermatology due to destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, but few studies have investigated the cell types and function of circulating immune cells in peripheral blood. Here, single cell RNA-sequencing (scRNA-seq) was used to investigate the mechanisms of peripheral immune responses in vitiligo patients.MethodsPeripheral blood was collected from five patients with progressive non-segmental vitiligo and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Paque density gradient centrifugation, and scRNA-seq was performed on isolated cell populations to obtain single cell transcriptomes and characterize important genes and intracellular signaling pathways. The key findings were validated with qPCR and flow cytometry assays.ResultsWe identified 10 major cell types by scRNA-seq. Among these cell types, neutrophils were specifically observed in our scRNA-seq data from PBMCs. Peripheral blood effector CD8+ T cells from vitiligo patients did not show significant differences at the transcriptome level compared with healthy controls, whereas regulatory T cells showed pro-inflammatory TH1-like properties. Innate immune cells, including natural killer cells and dendritic cells, showed increased antigen processing and presentation as well as upregulated interferon responses. B cells, monocytes, and neutrophils all showed activation. B cells, especially memory B cells, had upregulated expression of genes related to humoral immunity. Monocytes showed production of proinflammatory cytokines and chemokines. Neutrophils showed strong chemokine ligand-receptor (L-R) pair (CXCR8-CXCR2) autocrine signaling pathway.ConclusionThis study revealed the genetic profile and signaling pathway characteristics of peripheral blood immune cells in vitiligo patients, providing new insights into its pathogenesis, which may facilitate identification of potential therapeutic targets

    Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

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    Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.Peer reviewe

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

    Hierarchical Modeling and Dynamic Analysis of Hoist System in Electric Mining Shovel

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    The hoist system of electric mining shovel (EMS) always encounters excessive vibration in present work. However, the shortage of suitable dynamic model has been the bottleneck of reducing vibration. In order to analyze the vibration of the EMS hoist system, a coupled dynamic model is proposed using the hierarchical modeling method, which contains couplings of bolt, bear, coupling, rope, and gear mesh. The components were equivalent to mass elements with several nodes corresponding to their structure. Considered helical gears and motors, a dynamic gear transmission model with couplings of bending, torsion, and axes was developed. Based on the dynamic model, the modal characteristics were calculated, and the vibration modes were classified to five types. Under the ripple drive torque simulated by Simulink, the dynamic characteristics of the hoist system in time domain and frequency domain were obtained using numerical integration with the Runge–Kutta method in Matlab. At last, the model validity was verified by contrasting the responses under actual test and the model. The dynamic model and study results can provide support for dynamic characteristic evaluation and dynamic optimization of the EMS hoist system

    Additional file 1 of Metagenomic sequencing reveals altered gut microbial compositions and gene functions in patients with non-segmental vitiligo

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    Additional file 1: Supplementary Table 1. Summary of statistics of α-diversity. Supplementary Table 2.  Summary of statistics of β-diversity. Supplementary Table 3.  Summary of statistics of different gut microbiome taxonomy between control and vitiligo. Supplementary Table 4.  The correlation between different microbial species and VIDA score. Supplementary Table 5. Analysis of bacterial taxa by using LEfSe analyses. Supplementary Table 6.  Analysis of KEGG pathway. Supplementary Table 7.   Analysis of metabolic pathways. Supplementary Table 8.  Microbial species selected based on nest cross-validation model

    Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

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    Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK1OK and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) <1 %) or low-frequency (1% <MAF <5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets
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