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>

A Serine12Stop mutation in PB1-F2 of the 2009 pandemic (H1N1) influenza A: a possible reason for its enhanced transmission and pathogenicity to humans

Muthannan A. Ramakrishnan,Marie R. Gramer,Sagar M. Goyal,Srinand Sreevatsan 대한수의학회 2009 JOURNAL OF VETERINARY SCIENCE Vol.10 No.4

As the scientific community scrambles to define the ancestry and lineages of the eight segments of new pandemic H1N1 strain, we looked for unique genetic events in this virus’s genome to explain the newly found enhanced virulence and transmissibility among humans. Genome annotations of this virus identified a stop mutation replacing serine at codon 12 (S12Stop) of the PB1-F2 protein, a virulence factor in influenza A viruses. Here, we discuss the significance of this finding and how it may contribute to host specialization, explaining the virtual absence of the H1N1 influenza A virus strain in pig populations. This finding is expected to lead to a better understanding of the transmission and pathogenesis of the 2009 pandemic strain.

Fluorescence Enhancement of a Microbial Rhodopsin via Electronic Reprogramming

Marí,n, Marí,a del Carmen,Agathangelou, Damianos,Orozco-Gonzalez, Yoelvis,Valentini, Alessio,Kato, Yoshitaka,Abe-Yoshizumi, Rei,Kandori, Hideki,Choi, Ahreum,Jung, Kwang-Hwan,Haacke, Stefan American Chemical Society 2019 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.141 No.1

<P>The engineering of microbial rhodopsins with enhanced fluorescence is of great importance in the expanding field of optogenetics. Here we report the discovery of two mutants (W76S/Y179F and L83Q) of a sensory rhodopsin from the cyanobacterium <I>Anabaena</I> PCC7120 with opposite fluorescence behavior. In fact, while W76S/Y179F displays, with respect to the wild-type protein, a nearly 10-fold increase in red-light emission, the second is not emissive. Thus, the W76S/Y179F, L83Q pair offers an unprecedented opportunity for the investigation of fluorescence enhancement in microbial rhodopsins, which is pursued by combining transient absorption spectroscopy and multiconfigurational quantum chemistry. The results of such an investigation point to an isomerization-blocking electronic effect as the direct cause of instantaneous (subpicosecond) fluorescence enhancement.</P> [FIG OMISSION]</BR>

Hay' problemas

Jose‘ Mari‘a Areta Ayuso 한국스페인어문학회 2004 스페인어문학 Vol.0 No.33

Estudiamos en este trabajo la sintaxix del verbo haber como existencial. Para ello, nos basamos tanto en los ejemplos en los que este verbo concuerda con su complemento nominal como en los que no existe tal concordanci´a (los normativos). Discutimos la hipo´tesis de que este verbo sea un verbo inacusativo y la rechazamos segu´n criterios sinta´cticos como la posicio´n del argumento. Planteamos despune´s la hipo´tesis de que este verbo impersonal existencial en realidad proyecta dos argumentos, uno LOCATIVO y otro nominal. Aunque ha habido autores que han defendido el CASO PARTITIVO para este complemento, nosotros creemos que es ACUSATIVO, incluso en las ocasiones en que se produce su concordancia con el verbo, ya que se producen en espan~ol casos simiares, como con el verbo ser en oraciones como son las dos. Por u´ltimo, intentamos extender nuestra hipo´tesis a todos los verbos impersonales del espan~ol, y en esta clase incluimos dos subcategori´as, los impersonales le´xicos, como haber, estar, ser, existir, etc, y los impersinales sinta´cticos estructuras que se convierten en impersonales so´lo si aparece un argumento espacio-temporal. Aunque parece que no es necesario en todos los casos que el sintagma espacio-temporal este´ en una posicio´n argumental, si´ es necesario que estev presinte o, al menos, sea interpretable contextualmente.

PERCEIVED SUSTAINABILITY INITIATIVES: RETAIL MANAGERS’ INTRINSIC AND EXTRINSIC MOTIVES

Jos Bartels,Machiel J. Reinders,Mariët A. van Haaster-de Winter 글로벌지식마케팅경영학회 2014 Global Marketing Conference Vol.2014 No.8

In the past few decades, much attention has been focused on corporate social responsibility (CSR) (Dahlrud, 2008; McWilliams & Siegel, 2001; Maignan & Ralston, 2002; Montiel, 2008), consumer responses to CSR initiatives (Brown & Dacin, 1997; Sen & Bhattacharya, 2001) and more recently, employee attitudes towards CSR (Kim et al., 2010; Michailides & Lipsett, 2012; Rupp et al., 2006; Zhu et al., 2012). Although awareness of environmental sustainability has increased over the past few decades, the current market share of sustainable products remains low. Because of their market position, large-scale and high- volume customer interactions (Vella et al., 2009), supermarkets appear to be appropriate venues for investigating perceived sustainability initiatives (Hampl & Loock, 2013). Our study examined the extent to which supermarkets are perceived to have embedded sustainability initiatives in their marketing strategies and to have taken sustainable tactical measures on the store floor. In addition, the study considered the roles played by social identification (as an indicator for intrinsic motives) and by perceived external prestige (as an indicator for extrinsic motives). Based on a literature review and semi-structured qualitative interviews with the chief executive officers (CEOs) of Dutch supermarkets (n = 8), we conducted an online panel survey among the managers of these supermarkets (n = 99). The results of the qualitative study show that although CEOs’ opinions differed regarding the relevance of sustainability, the majority of CEOs indicated that the implementation of a sustainability strategy is strongly dependent on the intrinsic motivation of board members, the family business in general or local entrepreneurs (supermarket managers). Specifically, the role of the supermarket manager was recognized as important concerning sustainability initiatives on the shop floor. The results of the quantitative study show the positive impacts of managers’ social identification with a sustainable consumer group and managers’ perceived external prestige on the perceived environmental sustainability initiatives of Dutch supermarkets. The study finds that managers’ social identifications are powerful ways to engender employee loyalty. Moreover, organizations that are perceived to have more external prestige are perceived as being more capable of developing sustainability policies.

The hepatokine FGF21 is crucial for peroxisome proliferator-activated receptor-α agonist-induced amelioration of metabolic disorders in obese mice

Goto, Tsuyoshi,Hirata, Mariko,Aoki, Yumeko,Iwase, Mari,Takahashi, Haruya,Kim, Minji,Li, Yongjia,Jheng, Huei-Fen,Nomura, Wataru,Takahashi, Nobuyuki,Kim, Chu-Sook,Yu, Rina,Seno, Shigeto,Matsuda, Hideo,A American Society for Biochemistry and Molecular Bi 2017 The Journal of biological chemistry Vol.292 No.22

<P>Obesity causes excess fat accumulation in white adipose tissues (WAT) and also in other insulin-responsive organs such as the skeletal muscle, increasing the risk for insulin resistance, which can lead to obesity-related metabolic disorders. Peroxisome proliferator-activated receptor-alpha (PPAR alpha) is a master regulator of fatty acid oxidation whose activator is known to improve hyperlipidemia. However, the molecular mechanisms underlying PPAR alpha activator-mediated reduction in adiposity and improvement of metabolic disorders are largely unknown. In this study we investigated the effects of PPAR alpha agonist (fenofibrate) on glucose metabolism dysfunction in obese mice. Fenofibrate treatment reduced adiposity and attenuated obesity-induced dysfunctions of glucose metabolism in obese mice fed a high-fat diet. However, fenofibrate treatment did not improve glucose metabolism in lipodystrophic A-Zip/F1 mice, suggesting that adipose tissue is important for the fenofibrate-mediated amelioration of glucose metabolism, although skeletal muscle actions could not be completely excluded. Moreover, we investigated the role of the hepatokine fibroblast growth factor 21 (FGF21), which regulates energy metabolism in adipose tissue. In WAT of WT mice, but not of FGF21-deficient mice, fenofibrate enhanced the expression of genes related to brown adipocyte functions, such as Ucp1, Pgc1a, and Cpt1b. Fenofibrate increased energy expenditure and attenuated obesity, whole body insulin resistance, and adipocyte dysfunctions in WAT in high-fat-diet-fed WT mice but not in FGF21-defi-the fenofibrate-mediated improvement of whole body glucose metabolism in obese mice via the amelioration of WAT dysfunctions.</P>

Composition and Evaluation of the Anti-Inflammatory and Anticancer Activities of the Essential Oil from Annona sylvatica A. St.-Hil

Anelise S.N. Formagio,Maria do Carmo Vieira,Luiz A.C. dos Santos,Clau´dia A.L. Cardoso,Mary Anny Foglio,Joao Ernesto de Carvalho,Magaiver Andrade-Silva,Caˆndida A.L. Kassuya 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.1

The essential oil from the leaves of Annona sylvatica (EOAS) was extracted by hydrodistillation, and the analysis was performed by gas chromatography–mass spectrometry. The main compounds identified in the EOAS were sesquiterpenes, such as hinesol, z-caryophyllene, β-maaliene, γ-gurjunene, silphiperfol-5-en-3-ol, ledol, cubecol-1-epi, and muurola-3,5-diene. Oral administration of the EOAS (20 and 200 mg/kg) and subcutaneous injection of dexamethasone (0.5 mg/kg, reference drug) significantly inhibited carrageenan- and complete Freund's adjuvant–induced mouse paw edema. The anticancer activity the EOAS showed growth inhibitory activity on all cell lines when administered in a high concentration. The EOAS inhibited the growth of human cancer cell lines with GI50 values in the range of 36.04–45.37 μg/mL on all of the cell lines tested. This work describes for the first time the anti-inflammatory and anticancer effects of the essential oil of A. sylvatica and its composition. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side-effects, the present results may have clinical relevance and open new possibilities for the development of novel anti-inflammatory and anticancer drugs.

Effect of Pressure on the Intermediate-valence Semiconductor SmB6 : 11B-NMR

Kohei Nishiyama,Takeshi Mito,Ko-ichi Ueda,Takehide Koyama,Takao Kohara,Gabriel Prist´aˇs,Slavom´ır Gab´ani,Mari´an Reiffers,Karol Flachbart,Yasuhiro Komaki,Mitsutane Kokubu,Hideto Fukazawa,and Yoh Koh 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.62 No.12

We report the first high-pressure 11B-NMR studies above 3 GPa on the intermediate-valencesemiconductor SmB6. A 11B-NMR line obtained at 4.9 GPa, the highest pressure for the measurements,and at 1.9 K shows quite similar a line shape to that at ambient pressure, indicating nostructural or magnetic phase transition up to this pressure. The temperature dependence of thespin lattice relaxation rate 1/T1 at 4.9 GPa still exhibits an activation-type temperature dependencecharacteristic of semiconductors, which reveals an obvious decrease in the insulating gap byabout 30% compared to the gap at ambient pressure. The present experimental facts of a finiteinsulator gap and no magnetic order at 4.9 GPa are consistent with recent transport measurementsperformed under better hydrostatic pressures.

Localization techniques in quantum field theories

Pestun, Vasily,Zabzine, Maxim,Benini, Francesco,Dimofte, Tudor,Dumitrescu, Thomas T,Hosomichi, Kazuo,Kim, Seok,Lee, Kimyeong,Le Floch, Bruno,Mariñ,o, Marcos,Minahan, Joseph A,Morrison, David R,P IOP 2017 JOURNAL OF PHYSICS A-MATHEMATICAL AND THEORETICAL Vol.50 No.44

<P>This is the foreword to the special issue on localization techniques in quantum field theory. The summary of individual chapters is given and their interrelation is discussed.</P>

The loss of phenol sulfotransferase 1 in hepatocellular carcinogenesis

Yeo, Marie,Mi Na, Young,Kyu Kim, Dong,Bae Kim, Young,Jeong Wang, Hee,Lee, Jung A.,Youn Cheong, Jae,Jae Lee, Kwang,Paik, Young-Ki,Won Cho, Sung WILEY-VCH Verlag 2010 Proteomics Vol.10 No.2

<P>Biomarkers for the detection of early hepatocellular carcinoma (HCC) are urgently needed. To identify biomarkers of HCC, we performed a comparative proteomics analysis, based on 2-DE of HCC tissues and surrounding non-tumor tissues. Six xenobiotic enzymes were significantly down-regulated in the HCC tissue. Among these, phenol sulfotransferase (SULT1A1) was confirmed by Western blot analysis in 105 HCC patients. SULT1A1 showed a significant decrease in 98.1% of the HCC tissues, with 88.6% sensitivity and 66.7% specificity for the detection of HCC. Immunohistochemistry for SULT1A1 was performed and compared with glypican-3, which is a well-known marker of HCC. The results showed down-regulation of SULT1A1 and up-regulation of glypican-3 in 52.6 and 71.9% of the HCCs, and the use of both markers improved the sensitivity up to 78.9%. Moreover, SULT1A1 was useful in differentiating early HCC from benign dysplastic nodules. Clinically, the down-regulation of SULT1A1 was closely associated with an advanced International Union Against Cancer stage and high levels of serum α-fetoprotein. In conclusion, the results of this study demonstrate that the loss of SULT1A1 appears to be a characteristic molecular signature of HCC. SULT1A1 might be a useful biomarker for the detection of early HCC and help predict the clinical outcome of patients with HCC.</P>