Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations

Okada, Yukinori,Kim, Kwangwoo,Han, Buhm,Pillai, Nisha E.,Ong, Rick T.-H.,Saw, Woei-Yuh,Luo, Ma,Jiang, Lei,Yin, Jian,Bang, So-Young,Lee, Hye-Soon,Brown, Matthew A.,Bae, Sang-Cheol,Xu, Huji,Teo, Yik-Yin Oxford University Press 2014 Human Molecular Genetics Vol.23 No.25

<P>Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DRβ1 at amino acid position 13, located outside the classical shared epitope (<I>P</I><SUB>omnibus</SUB> = 6.9 × 10<SUP>−135</SUP>). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr ≅ Gly > Ser)—but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional <I>P</I><SUB>omnibus</SUB> = 2.2 × 10<SUP>−33</SUP>) and 74 (conditional <I>P</I><SUB>omnibus</SUB> = 1.1 × 10<SUP>−8</SUP>). Outside of HLA-DRβ1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional <I>P</I> = 3.8 × 10<SUP>−6</SUP>) and HLA-DPβ1 (Phe9, conditional <I>P</I> = 3.0 × 10<SUP>−5</SUP>) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino acid residues confer shared effects in European and Asian populations and (ii) these same effects can explain ethnically heterogeneous classical allelic associations (e.g. <I>HLA-DRB1*09:01</I>) due to allele frequency differences between populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC.</P>

Taiwan Neurosurgical Spine Society: Move Together in “Neurospine” Toward Clinical and Academic Success

E-Jian Lee 대한척추신경외과학회 2018 Neurospine Vol.15 No.1

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Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility

Zhao, Jian,Wu, Hui,Khosravi, Melanie,Cui, Huijuan,Qian, Xiaoxia,Kelly, Jennifer A.,Kaufman, Kenneth M.,Langefeld, Carl D.,Williams, Adrienne H.,Comeau, Mary E.,Ziegler, Julie T.,Marion, Miranda C.,Adl Public Library of Science 2011 PLoS genetics Vol.7 No.5

<▼1><P>Systemic lupus erythematosus (SLE), a complex polygenic autoimmune disease, is associated with increased complement activation. Variants of genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) within the chromosome 1q32 locus linked to SLE, have been associated with multiple human diseases and may contribute to dysregulated complement activation predisposing to SLE. We assessed 60 SNPs covering the <I>CFH</I>-<I>CFHRs</I> region for association with SLE in 15,864 case-control subjects derived from four ethnic groups. Significant allelic associations with SLE were detected in European Americans (EA) and African Americans (AA), which could be attributed to an intronic <I>CFH</I> SNP (rs6677604, in intron 11, <I>P</I><SUB>meta</SUB> = 6.6×10<SUP>−8</SUP>, OR = 1.18) and an intergenic SNP between <I>CFHR1</I> and <I>CFHR4</I> (rs16840639, <I>P</I><SUB>meta</SUB> = 2.9×10<SUP>−7</SUP>, OR = 1.17) rather than to previously identified disease-associated <I>CFH</I> exonic SNPs, including I62V, Y402H, A474A, and D936E. In addition, allelic association of rs6677604 with SLE was subsequently confirmed in Asians (AS). Haplotype analysis revealed that the underlying causal variant, tagged by rs6677604 and rs16840639, was localized to a ∼146 kb block extending from intron 9 of <I>CFH</I> to downstream of <I>CFHR1</I>. Within this block, the deletion of <I>CFHR3</I> and <I>CFHR1</I> (<I>CFHR3-1</I>Δ), a likely causal variant measured using multiplex ligation-dependent probe amplification, was tagged by rs6677604 in EA and AS and rs16840639 in AA, respectively. Deduced from genotypic associations of tag SNPs in EA, AA, and AS, homozygous deletion of <I>CFHR3-1</I>Δ (<I>P</I><SUB>meta</SUB> = 3.2×10<SUP>−7</SUP>, OR = 1.47) conferred a higher risk of SLE than heterozygous deletion (<I>P</I><SUB>meta</SUB> = 3.5×10<SUP>−4</SUP>, OR = 1.14). These results suggested that the <I>CFHR3-1</I>Δ deletion within the SLE-associated block, but not the previously described exonic SNPs of <I>CFH</I>, might contribute to the development of SLE in EA, AA, and AS, providing new insights into the role of complement regulators in the pathogenesis of SLE.</P></▼1><▼2><P><B>Author Summary</B></P><P>Systemic lupus erythematosus (SLE) is a complex autoimmune disease, associated with increased complement activation. Previous studies have provided evidence for the presence of SLE susceptibility gene(s) in the chromosome 1q31-32 locus. Within 1q32, genes encoding complement regulator factor H (CFH) and five CFH-related proteins (CFHR1-CFHR5) may contribute to the development of SLE, because genetic variants of these genes impair complement regulation and predispose to various human diseases. In this study, we tested association of genetic variants in the region containing <I>CFH</I> and <I>CFHRs</I> with SLE. We identified genetic variants predisposing to SLE in European American, African American, and Asian populations, which might be attributed to the deletion of <I>CFHR3</I> and <I>CFHR1</I> genes but not previously identified disease-associated exonic variants of <I>CFH</I>. This study provides the first evidence for consistent association between <I>CFH/CFHRs</I> and SLE across multi-ancestral SLE datasets, providing new insights into the role of complement regulators in the pathogenesis of SLE.</P></▼2>

Numerical Simulation of BOR scattering and radiation using a higher order FEM

Dunn, E.A.,Jin-Kyu Byun,Branch, E.D.,Jian-Ming Jin Institute of Electrical and Electronics Engineers 2006 IEEE transactions on antennas and propagation Vol.54 No.3

<P>Numerical simulations of body-of-revolution geometries for scattering and radiation problems are presented. The formulation consists of a finite element-boundary integral (FE-BI) method which is based on a finite element method that uses higher order nodal-based scalar basis functions for the azimuthal field component and higher order edge-based vector basis functions for the transverse field. This formulation, when combined with a symmetric FE-BI hybridization scheme, yields a final system of equations that is more accurate than earlier first-order formulations. Numerical examples are given to demonstrate the accuracy and capabilities of the higher order solution</P>

Allergic Identification for Ginkgo Kernel Protein in Guinea Pigs

Cai-e Wu,Jian-Ting Yang,Gong-Jian Fan,Ting-Ting Li,Zhen-Xing Tang,Fu-Liang Cao 한국식품과학회 2016 Food Science and Biotechnology Vol.25 No.3

Ginkgo biloba L. can cause allergic reactions when consumed. In this paper, an allergy test to guinea pig was investigated. Guinea pigs were sensitized with 50 mg/mL of ginkgo kernel protein orally on days 1, 3, and 5, and intraperitoneally challenged with 100mg/mL of the protein on day 7 after the last sensitization. The volume of sensitization and challenge was 0.20mL/100 g weight. The results showed the average allergy grade for guinea pigs reached four and the allergy rate was 100%. The immunoglobulin G and E levels in sera were significantly higher than those in the controls. Footpads swelled distinctly, and the passive cutaneous allergy test manifested a positive response. There were inflammatory changes in the lungs and intestines. In conclusion, the present results may indicate that gingko kernel protein has an allergenic capacity.

Isolation of a Natural Antioxidant, Dehydrozingerone from Zingiber officinale and Synthesis of lts Analogues for Recognition of Effective Antioxidant and Antityrosinase Agents

Kuo, Ping-Chung,Damu, Amooru G.,Cherng, Ching-Yuh,Jeng, Jye-Fu,Teng, Che-Ming,Lee, E-Jian,Wu, Tian-Shung The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.5

In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. Rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive co mponents of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe$^{2+}$-induced lipid peroxidation in rat brain homogenate with an IC$_{50}$ = 6.3${\pm}$0.4 ${\mu}$M. In the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like ${\alpha}$-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4- dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.

Multiple functional self-association interfaces in plant TIR domains

Zhang, Xiaoxiao,Bernoux, Maud,Bentham, Adam R.,Newman, Toby E.,Ve, Thomas,Casey, Lachlan W.,Raaymakers, Tom M.,Hu, Jian,Croll, Tristan I.,Schreiber, Karl J.,Staskawicz, Brian J.,Anderson, Peter A.,Soh National Academy of Sciences 2017 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.114 No.10

<P>The self-association of Toll/interleukin-1 receptor/resistance protein (TIR) domains has been implicated in signaling in plant and animal immunity receptors. Structure-based studies identified different TIR-domain dimerization interfaces required for signaling of the plant nucleotide-binding oligomerization domain-like receptors (NLRs) L6 from flax and disease resistance protein RPS4 from Arabidopsis. Here we show that the crystal structure of the TIR domain from the Arabidopsis NLR suppressor of npr1-1, constitutive 1 (SNC1) contains both an L6-like interface involving helices alpha D and alpha E (DE interface) and an RPS4-like interface involving helices alpha A and alpha E (AE interface). Mutations in either the AE- or DE-interface region disrupt cell-death signaling activity of SNC1, L6, and RPS4 TIR domains and full-length L6 and RPS4. Self-association of L6 and RPS4 TIR domains is affected by mutations in either region, whereas only AE-interface mutations affect SNC1 TIR-domain self-association. We further show two similar interfaces in the crystal structure of the TIR domain from the Arabidopsis NLR recognition of Peronospora parasitica 1 (RPP1). These data demonstrate that both the AE and DE self-association interfaces are simultaneously required for self-association and cell-death signaling in diverse plant NLRs.</P>

Isolation of a Natural Antioxidant, Dehydrozingerone from Zingiber officinale and Synthesis of Its Analogues for Recognition of Effective Antioxidant and Antityrosinase Agents

Ping-Chung Kuo,Amooru G. Damu,Ching-Yuh Cherng,Jye-Fu Jeng,Che-Ming Teng,E-Jian Lee,Tian-Shung Wu 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.5

In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. rhizomes- derived materials (on mushroom tyrosinase) were evaluated. The bioactive components of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe2+-induced lipid peroxidation in rat brain homogenate with an IC50 = 6.3±0.4 µM. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like α-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4- dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.

VISUALIZATION ON VORTEX OF CROSS FLOW PAST A CIRCULAR CYLINDER NEAR A WALL BY PIV

JIAN WU,HUANG SHE-HUA,QI E-RONG,WEI LI 한국수자원학회 2005 한국수자원학회 학술대회 Vol.2005 No.1

Imaging Spectrum after Pancreas Transplantation with Enteric Drainage

Jian-Ling Chen,Rheun-Chuan Lee,Yi-Ming Shyr,Sing-E Wang,Hsiuo-Shan Tseng,Hsin-Kai Wang,Shan-Su Huang,Cheng-Yen Chang 대한영상의학회 2014 Korean Journal of Radiology Vol.15 No.1

Since the introduction of pancreas transplantation more than 40 years ago, surgical techniques and immunosuppressive regiments have improved and both have contributed to increase the number and success rate of this procedure. However, graft survival corresponds to early diagnosis of organ-related complications. Thus, knowledge of the transplantation procedure and postoperative image anatomy are basic requirements for radiologists. In this article, we demonstrate the imaging spectrum of pancreas transplantation with enteric exocrine drainage.