Interferon regulatory factor 7 (IRF7) has an essential role in the production of type I interferon. Although recent studies detected association of a single nucleotide polymorphism (SNP) rs4963128 in ...PHD and ring finger domains 1 (PHRF1)/KIAA1542, located closely to IRF7, and IRF7 rs1131665 (glutamine (Gln) 412 arginine (Arg)) with systemic lupus erythematosus (SLE), causal variants have not been established. In this study, we resequenced exons and introns of IRF7 to screen for all common polymorphisms, and examined whether they were associated with SLE in 416 Japanese patients with SLE and 505 healthy controls. We also tested whether the association of PHRF1 rs4963128 with SLE was replicated in a Japanese population. None of the IRF7 polymorphisms was associated with SLE. PHRF1 rs4963128T was not significantly associated with occurrence of SLE either; however, this allele was significantly increased in SLE with anti-Sm antibodies (6.8%) as compared with healthy controls (3.1%, P = 0.014, odds ratio OR 2.31) and SLE without anti-Sm antibodies (3.3%, P =0.041, OR 2.12). This allele was also increased in SLE with renal disorder (5.1%) as compared with those without renal disorder (2.4%, P = 0.047, OR 2.17). These results confirmed recently reported association of PHRF1 rs4963128T with anti-Sm antibody positive SLE in African-American populations, and supported the role of PHRF1-IRF7 region in the genetics of SLE.
We investigated the effect of all-trans-retinoic acid (atRA) on proliferation in several human skin cell lines and found that antiproliferative potency of atRA correlated with the endogenous activity ...of canonical Wnt signaling. In HaCaT keratinocytes, we found that atRA significantly suppressed the expression of Id2, a member of the inhibitor of differentiation family of transcription factors that regulate cell growth and differentiation. However, no apparent change in the expression of other Wnt targets, like c-Myc or cyclin D1, was observed. Retinoid-induced Id2 gene suppression was associated with decreased levels of histone H3 and H4 acetylation and histone H3 Lys-4 methylation, and with recruitment of the LSD1 demethylase at the Wnt-response element (WRE) (TCF/LEF-binding site), in the Id2 gene promoter. None of such changes was detected at the WRE of c-Myc and cyclin D1 gene promoters. Inhibition of Id2 by short interfering RNA (siRNA) had a similar effect on the proliferation of HaCaT cells as exposure to atRA, whereas anti-beta-catenin siRNA significantly inhibited its antiproliferative effect. These data suggest that downregulation of Id2 gene expression through transcriptional convergence between Wnt and retinoid signaling pathways underlies the antiproliferative effect of retinoids in keratinocytes, and provide evidence of gene-targeted crosstalk between signaling pathways.
The Rh/CeO2/M (M = SiO2, Al2O3, and ZrO2) type catalysts with various compositions have been prepared and investigated in the gasification of cellulose, a model compound of biomass, in a fluidized ...bed reactor at 500−700 °C. The conventional nickel and dolomite catalysts have also been investigated. Among the catalysts, Rh/CeO2/SiO2 with 35% CeO2 has been found to be the best catalyst with respect to the carbon conversion to gas and product distribution. The steam addition contributed to the complete conversion of cellulose to gas even at 600 °C. Lower steam supply gave the syngas and higher steam supply gave the hydrogen as the major product. Hydrogen and syngas from cellulose or cellulosic biomass gasification are environmentally super clean gaseous fuels for power generation. Moreover, the syngas derived liquid fuels such as methanol, dimethyl ether, and synthetic diesels are also super clean transportation fuels. However, the use of cellulose or cellulosic biomass for energy source through the gasification is challenging because of the formation of tar and char during the gasification process. It is interesting that no tar or char was finally formed in the effluent gas at as low as 500−600 °C using Rh/CeO2/SiO2(35) catalyst in this process.
Nano-sized ZrO2/Cr2O3/carbon clusters composite materials were successfully obtained by the microwave-irradiated calcinations of a
Zr(acac)4/Cr(acac)3/epoxy resin complex. The compositions of the ...resulting composite materials were determined using ICP, elemental
analysis and surface characterization by XRD, SEM and TEM. The UV–Vis spectra of the composites were also obtained. ESR spectral
examinations of the composites indicate that an electron transfer takes place in the process Cr2O3 → carbon clusters → ZrO2. The composite
materials have been found to show visible light-responsive catalytic activities. KCI Citation Count: 23
Lysophosphatidylcholine (Lyso-PC) is generally considered to promote tissue inflammation. To determine the involvement of exogenous Lyso-PC in the beta-adrenergic desensitization by phospholipase A2, ...we examined the inhibitory effects of isoproterenol (ISO) on tension and intracellular Ca(2+) concentration by methacholine (MCh) after continuous exposure to Lyso-PC in guinea-pig tracheal smooth muscle, using isometric tension recordings and fura-2 signal (F340/F380 ratio). Pre- exposure to 10 microM Lyso-PC markedly reduced subsequent inhibition by 0.3 microM ISO against 1 microM MCh-induced contraction in a time-dependent manner. In contrast, values of percent F340/F380 ratio for MCh with ISO were not affected after exposure to Lyso-PC. In the presence of Y-27632, a selective rho-kinase inhibitor, a reduction in subsequent relaxation by ISO after exposure to Lyso-PC was inhibited in a concentration-dependent manner. Preincubation with cholera toxin also inhibited reduced responsiveness to ISO by Lyso-PC. Pre-exposure to Lyso-PC did not attenuate subsequent relaxation by agents that bypass beta-adrenergic receptors. These results indicate that continuous exposure to Lyso-PC may cause homologous desensitization of beta-adrenergic receptors via an augmentation in sensitivity to Ca(2+) by rho, a small G protein, in airway smooth muscle, and that activation of the stimulatory G protein of adenylyl cyclase, G(s), may prevent this phenomenon.
The panda mutant in Japanese quail (Coturnix japonica) displays spots of wild-type plumage on a white background and is controlled by an autosomal recessive allele (s). The dotted white is controlled ...by a third allele (sdw) of the s locus with sdw/sdw quail having less pigmentation than s/s quail. We mapped the s locus to the Japanese quail chromosome 4 (CJA04) in a previous study. The orthologous region of the chicken (Gallus gallus) genome includes endothelin receptor B2 (EDNRB2), an avian-specific paralog of endothelin receptor B (EDNRB). EDNRB mutations in mammals retard the migration of neural crest cells (NCCs), which results in a spotted coat colour and an enteric nervous defect. In the present study, we investigated the association between the s locus and EDNRB2 in Japanese quail. Sequence comparison among transcripts from livers of wild-type, panda and dotted white quail revealed a nucleotide substitution (c.995G>A) leading to a p.R332H amino acid change that was specific to panda, whereas no amino acid substitution was found in dotted white birds. The amino acid position 332 is located in the sixth transmembrane domain and is highly conserved in both avian and mammalian endothelin receptors. The A allele at nucleotide position 995 was specific to panda (s/s) birds among 10 strains, and was mapped to the same chromosomal region as the s locus. Quantitative RT-PCR revealed that EDNRB2 transcripts were reduced in both panda and dotted white mutants compared with wild-type. However, there was no difference between the early embryos of wild-type and panda with respect to the migration of NCCs. The genetic association of EDNRB2 with plumage colour in birds was found for the first time in this study.
The PIENU experiment aims to measure the branching ratio of the charged pion decay with precision of < 0.1 %. This measurement is much sensitive to search for massive neutrinos coupled to electrons ...in
π
+
→
e
+
ν
e
decay. The initial analysis was completed and the upper limit on the neutrino mixing parameter |
U
e
i
|
2
in the neutrino mass range of 0 to 55 MeV/
c
2
was improved by a factor of 1.5, and the sensitivity for the mass range of 68 to 129 MeV/
c
2
was improve by a factor of up to 4.