PSORS1 (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of PSORS1 where multiple biologically ...plausible candidate genes were suggested. The most recent study has indicated HLA-Cw6 as the primary PSORS1 risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the PSORS1 locus was performed by analyzing 10 polymorphic microsatellite markers from the PSORS1 region as well as HLA-B, HLA-C and CDSN loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P<10(-3)), and one marker locus shows weak evidence (P = 0.04) for association. The haplotype cluster analysis showed that all the risk haplotypes are Cw6 positive and share a 369-kb region of homologous marker alleles which carries all the risk alleles, including HLA-Cw6 and CDSN*TTC, identified in this study. The recombinant haplotype analysis of the HLA-Cw6 and CDSN*TTC alleles in 228 Chinese families showed that the HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotype is clearly not associated with risk for psoriasis (TratioNT = 29:57, p = 0.0025) in a Chinese population, suggesting that the CDSN*TTC allele itself does not confer risk without the presence of the HLA-Cw6 allele. The further exclusion analysis of the non-risk HLA-Cw6(-)/CDSN*TTC(+) recombinant haplotypes with common recombination breakpoints has allowed us to refine the location of PSORS1 to a small candidate region. Finally, we performed a conditional linkage analysis and showed that the HLA-Cw6 is a major risk allele but does not explain the full linkage evidence of the PSORS1 locus in a Chinese population. By performing a series of family-based association analyses of haplotypes as well as an exclusion analysis of recombinant haplotypes, we were able to refine the PSORS1 gene to a small critical region where HLA-C is a strong candidate to be the PSORS1 susceptibility gene.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Psoriasis has long been considered as a complex disease, and gene–gene or gene–environment interactions may jointly influence the etiology for psoriasis. Objective We evaluated ...the associations of single nucleotide polymorphisms (SNPs) in MHC region, and determined the epistasis and combined effects of MHC locus and IL12B , LCE on risk for psoriasis. Methods We genotyped SNP rs1265181 (MHC) in 5067 cases and 6404 controls, combining with the prior GWAS data (1139 cases and 1132 controls), we explored the genetic interaction among MHC locus, LCE and IL12B by using logistic regression analysis. We evaluated the combined effects of MHC locus and two non-MHC loci in the combined sample of 6206 cases and 7536 controls. Results Extremely high significance of association was detected between rs1265181 and psoriasis ( p combined <10E−300, OR = 16.52, 95% CI: 15.28–18.44). We observed significant interactions between MHC and LCE ( p = 0.0016) and between MHC and IL12B ( p = 0.0036). The risk increased some 26-fold in individuals with risk alleles in both MHC and LCE as compared with those without risk alleles, and individual carrying risk alleles of MHC and IL12B has around 36-fold higher risk of psoriasis than those with protective alleles. Conclusions This study provides evidence for the epistatic effects between MHC locus and LCE , IL12B genes. Besides, we suggest that MHC might be the main effect gene on the risk for psoriasis. This data may contribute to our understanding of psoriasis genetic interactions and account for the additional risk of certain patients to develop psoriasis.
Wearable electronics, as essential components of the Internet of Things (IoT), have attracted widespread attention, and the trend is to configure attractive wearable smart microsystems by integrating ...sensing, powering, and other functions. Herein, we developed an elastic hybrid triboelectric-electromagnetic microenergy harvester (named EHTE) to realize hybrid sensing and microenergy simultaneously. This EHTE is a highly integrated triboelectric nanogenerator (TENG) and electromagnetic nanogenerator (EMG). Based on the triboelectric-electromagnetic hybrid mechanism, an enhanced electrical output of the EHTE was achieved successfully, which demonstrates the feasibility of the EHTE for microelectronics powering. Moreover, with the merits of the EMG, the developed hybrid microenergy harvester integrated both active frequency sensing and passive inductive sensing capabilities. Specifically, the almost linear correlation of the electromagnetic outputs to the frequencies of the external stimulus endowed the proposed EHTE with an outstanding active frequency sensing ability. In addition, due to the unique structural configuration of the EMG (i.e., a conductive permanent magnet (PM), hybrid deformation layer, and flexible printed circuit board (FPCB) coil), an opportunity was provided for the developed EHTE to serve as a passive inductive sensor based on the eddy current effect (i.e., a form of electromagnetic induction). Therefore, the developed EHTE successfully achieved the integration of hybrid sensing (i.e., active frequency sensing and passive inductive sensing) and microenergy (i.e., the combination of electromagnetic effect and triboelectric effect) within a single device, which demonstrates the potential of this newly developed EHTE for wearable electronic applications, especially in applications of compact active microsystems.
Abstract
Behect’s disease is a chronic vasculitis characterized by complex multi-organ immune aberrations. However, a comprehensive understanding of the gene-regulatory profile of peripheral ...autoimmunity and the diverse immune responses across distinct cell types in Behcet’s disease (BD) is still lacking. Here, we present a multi-omic single-cell study of 424,817 cells in BD patients and non-BD individuals. This study maps chromatin accessibility and gene expression in the same biological samples, unraveling vast cellular heterogeneity. We identify widespread cell-type-specific, disease-associated active and pro-inflammatory immunity in both transcript and epigenomic aspects. Notably, integrative multi-omic analysis reveals putative TF regulators that might contribute to chromatin accessibility and gene expression in BD. Moreover, we predicted gene-regulatory networks within nominated TF activators, including AP-1, NF-kB, and ETS transcript factor families, which may regulate cellular interaction and govern inflammation. Our study illustrates the epigenetic and transcriptional landscape in BD peripheral blood and expands understanding of potential epigenomic immunopathology in this disease.
The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) ...responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.
NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.
We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.
Species in transformed habitats, frequently labeled as environmental generalists, tend to show broader niches than species in natural habitats. However, how population niche expansion translates into ...changes in the niches of individual organisms remains unclear, particularly in the context of habitat transformation. Niche expansion could be a product of individuals having broader niches, greater distances among individuals’ niches, or a combination of both processes. This would challenge the traditional conceptions on niche dynamics, which emphasize the role played by individual specialization (IS). Here, using stable isotopes, we computed total niche width (TNW), its within- and between-individual components (WIC and BIC), and IS (the ratio WIC/TNW), in 13 populations of 6 bird species and 8 populations of 3 frog species in natural and transformed habitats. We confirmed that species had broader niche width in transformed than in natural habitats, yet population niche expansion across habitats was mainly a product of increased distance between individuals. Within each habitat type, increases in TNW were linked to increases in WIC for all habitat types, while relationships between TNW and BIC were found in transformed but not in natural habitats. Hence, both increased individual niche width and increased distance among individuals were apparent within habitats, particularly in transformed ones, where increases in WIC dominated. Neither across or within habitats was niche expansion associated with increasing IS. Therefore, our results overturn traditional conceptions associated with the niche variation hypothesis and illustrate that niche expansion is not invariably associated with increased IS, because the distance between individual’s niches (BIC) can increase, as well as the breadth of those niches (WIC).
During the traditional homogeneous Fenton reaction process for water treatment, the consumption rate constant of Fe
2+
is much greater than its regeneration rate constant, which makes Fe
2+
an almost ...stoichiometric loss and produces iron sludge waste. In this article, highly dispersed zero-valent Fe nanoparticles loaded on porous carbon materials (Fe-EMC) were synthesized by a one-step calcination method using
Flammulina velutipes
natural carbon source and Fe(NO
3
)
3
as raw materials to solve the aforementioned problem. The as-prepared Fe-EMC materials are characterized by X-ray diffraction analysis, scanning electron microscopy, electron probe microanalyzer, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and N
2
adsorption–desorption measurements. It exhibits excellent photocatalytic activity for the degradation of methylene blue (MB) dyes under a broad pH region. Under conditions of 0.3 g/L Fe-EMC, 0.2 M/L H
2
O
2
, pH 7.0–11.0, and 50 mg/L MB, 97.98% of the MB dyes in the solution were completely degraded within 1 h. It was attributed to the efficient regeneration cycle between Fe
2+
and Fe
3+
in the Fenton-like system with light irradiation, which can promote the generation of active oxygen species.
We have performed a large-scale replication study based on our previous genome-wide association study (GWAS) of SLE in the Chinese Han population to further explore additional genetic variants ...affecting susceptibility to SLE.
Thirty-eight single nucleotide polymorphisms from our GWAS were genotyped in two additional Chinese Han cohorts (total 3152 cases and 7050 controls) using the Sequenom Massarray system. Association analyses were performed using logistic regression with gender or sample cohorts as a covariate.
Association evidence for rs16972959 (PRKCB at 16p11.2) and rs12676482 (8p11.21) with SLE was replicated independently in both replication cohorts (P < 0.05), showing high significance for SLE in combined all 4199 cases and 8255 controls of Chinese Han rs16972959: odds ratio (OR) = 0.81; 95% CI 0.76, 0.87; P(combined) = 1.35 × 10(-9); rs12676482: OR = 1.26; 95% CI 1.15, 1.38; P(combined) = 6.68 × 10(-7)). PRKCB is related to the established SLE immune-related pathway (NF-κB) and 8p11.21 contains important candidate genes such as IKBKB and DKK4. IKBKB is a critical component of NF-κB and DKK4 is an inhibitor of canonical Wnt signalling pathway. Interestingly, PRKCB is required for recruiting IKBKB into lipid rafts, up-regulating NF-κB-dependent survival signal.
Our findings provided novel insights into the genetic architecture of SLE and emphasized the contribution of multiple variants of modest effect. Further study focused on PRKCB, 8p11.21, should advance our understanding on the pathogenesis of SLE.
The calcicole or calcifuge behavior of wild plants has been related to element deficiency or toxicity. For fern species, however, knowledge about their adaptive differences and responses to soil ...environmental changes is virtually absent. In the karst regions of southern China, most Adiantum species favor calcareous soils, but A. flabellulatum prefers acidic soils. Such contrasting preferences for soil types in the same genus are interesting and risky because their preferred soils may "pollute" each other due to extreme precipitation events. We mixed calcareous and acidic soils at 1:1 (v/v) to simulate the "polluted" soils and grew three Adiantum species (the calcicole A. capillus-veneris f. dissectum and A. malesianum and the calcifuge A. flabellulatum) on the calcareous, acidic and mixed soils for 120 d and assessed their growth performance and element concentrations.
The calcareous soil showed the highest pH, Ca, Mg and P concentrations but the lowest K concentration, followed by the mixed soil, and the acidic soil. After 120 d of growth, the calcifuge A. flabellulatum on the calcareous and mixed soils exhibited lower SPAD and relative growth rate (RGR) than those on the acidic soil, and its leaf and root Ca, Mg and Fe concentrations were higher and K was lower on the calcareous soil than on the acidic soil. The calcicole A. capillus-veneris f. dissectum on the calcareous soil had similar leaf element concentrations and RGR with those on the mixed soil, but their leaf Ca, Fe and Al were lower and leaf P and K concentrations, SPAD and RGR were higher than those on the acidic soil. For the calcicole A. malesianum, leaf Ca, Fe and Al were lowest and leaf P and RGR were highest when grown on the mixed soil, intermediated on the calcareous soil, and on the acidic soil. Compared with A. malesianum, A. capillus-veneris f. dissectum had lower leaf Ca, Fe and Al but higher leaf Mg concentration when grown on the same calcareous or mixed soils.
A. capillus-veneris f. dissectum is a low leaf Ca calcicole species while A. malesianum is an Al accumulating calcicole species. They can effectively take up P and K to leaves and hence can thrive on calcareous soils. In contrast, the calcifuge A. flabellulatum grown on calcareous soils is stunted. Such growth performance may be attributed to the increased leaf Ca and decreased leaf K concentration. If their preferred soils are "polluted", A. flabellulatum can grow worse, A. capillus-veneris f. dissectum can remain almost unaffected while A. malesianum will perform better.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
