Summary To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of three genome-wide association studies (GWAS) and two independent datasets genotyped on the Immunochip, involving 10,588 cases and 22,806 controls in total. We identified 15 new disease susceptibility regions, increasing the number of psoriasis-associated loci to 36 for Caucasians. Conditional analyses identified five independent signals within previously known loci. The newly identified shared disease regions encompassed a number of genes whose products regulate T-cell function (e.g. RUNX3, TAGAP and STAT3). The new psoriasis-specific regions were notable for candidate genes whose products are involved in innate host defense, encoding proteins with roles in interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C), and NF-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.
A bioinspired, reusable, paper-based gold-nanoparticle film is fabricated by depositing an as-prepared gold-nanoparticle thin film on airlaid paper. This paper-based system with enhanced surface roughness and low thermal conductivity exhibits increased efficiency of evaporation, scale-up potential, and proven reusability. It is also demonstrated to be potentially useful in seawater desalination.
We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH (P < 10 −75), ARMS2 (P < 10 −59), C2/CFB (P < 10 −20), C3 (P < 10 −9 ), and CFI (P < 10 −6). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci (LIPC, P = 1.3 × 10 −7; CETP, P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c-associated alleles near LPL (P = 3.0 × 10 −3) and ABCA1 (P = 5.6 × 10 −4). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.genome-wide association study | single nucleotide polymorphism A ge-related macular degeneration (AMD) is a progressive neurodegenerative disease and a common cause of blindness in the elderly population, particularly in developed countries (1). The disease affects primarily the macular region of the retina, which is necessary for sharp central vision. An early hallmark of AMD is the appearance of drusen, which are extracellular deposits of proteins and lipids under the retinal pigment epithelium (RPE). As the disease progresses, drusen grow in size and number. In advanced stages of AMD, atrophy of the RPE (geographic atrophy) and/or development of new blood vessels (neovascularization) result in death of photoreceptors and central vision loss.
Ammonia has been used in important areas such as agriculture and clean energy. Its synthesis from the electrochemical reduction of N 2 is an attractive alternative to the industrial method that requires high temperature and pressure. Currently, electrochemical N 2 fixation has suffered from slow kinetics due to the difficulty of N 2 adsorption and NN cleavage. Here, N-doped porous carbon (NPC) is reported as a cost-effective electrocatalyst for ammonia synthesis from electrocatalytic N 2 reduction under ambient conditions, where its N content and species were tuned to enhance N 2 chemical adsorption and NN cleavage. The resulting NPC was effective for fixing N 2 to ammonia with a high ammonia production rate (1.40 mmol g −1 h −1 at −0.9 V vs RHE). Experiments combined with density functional theory calculations revealed pyridinic and pyrrolic N were active sites for ammonia synthesis and their contents were crucial for promoting ammonia production on NPC. The energy-favorable pathway for ammonia synthesis was *NN → *NHNH → *NH 2 −NH 2 → 2NH 3 .
Electrochemical reduction of CO2 is an attractive technique for reducing CO2 emission and converting it into useful chemicals, but it suffers from high overpotential, low efficiency or poor product selectivity. Here, N-doped nanodiamond/Si rod array (NDD/Si RA) was proposed as an efficient nonmetallic electrocatalyst for CO2 reduction. It preferentially and rapidly converted CO2 to acetate over formate with an onset potential of -0.36 V (vs RHE), overcoming the usual limitation of low selectivity for C2 products. Moreover, faradic efficiency of 91.2-91.8% has been achieved for CO2 reduction at -0.8 to -1.0 V. Its superior performance for CO2 reduction can be attributed to its high overpotential for hydrogen evolution and N doping, where N-sp(3)C species was highly active for CO2 reduction. Electrokinetic data and in situ infrared spectrum revealed the main pathway for CO2 reduction might be CO2 → CO2(•-) → (COO)2(•) → CH3COO(-).
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