Interactions between IL-32 and tumor necrosis factor alpha contribute to the exacerbation of immune-inflammatory diseases

IL-32 is a newly described cytokine in the human found to be an in vitro inducer of tumor necrosis factor alpha (TNFα). We examined the in vivo relationship between IL-32 and TNFα, and the pathologic role of IL-32 in the TNFα-related diseases – arthritis and colitis. We demonstrated by quantitative PCR assay that IL-32 mRNA was expressed in the lymphoid tissues, and in stimulated peripheral T cells, monocytes, and B cells. Activated T cells were important for IL-32 mRNA expression in monocytes and B cells. Interestingly, TNFα reciprocally induced IL-32 mRNA expression in T cells, monocyte-derived dendritic cells, and synovial fibroblasts. Moreover, IL-32 mRNA expression was prominent in the synovial tissues of rheumatoid arthritis patients, especially in synovial-infiltrated lymphocytes by in situ hybridization. To examine the in vivo relationship of IL-32 and TNFα, we prepared an overexpression model mouse of human IL-32β (BM-hIL-32) by bone marrow transplantation. Splenocytes of BM-hIL-32 mice showed increased expression and secretion of TNFα, IL-1β, and IL-6 especially in response to lipopolysaccharide stimulation. Moreover, serum TNFα concentration showed a clear increase in BM-hIL-32 mice. Cell-sorting analysis of splenocytes showed that the expression of TNFα was increased in resting F4/80(+ )macrophages, and the expression of TNFα, IL-1β and IL-6 was increased in lipopolysaccharide-stimulated F4/80(+ )macrophages and CD11c(+ )dendritic cells. In fact, BM-hIL-32 mice showed exacerbation of collagen-antibody-induced arthritis and trinitrobenzen sulfonic acid-induced colitis. In addition, the transfer of hIL-32β-producing CD4(+ )T cells significantly exacerbated collagen-induced arthritis, and a TNFα blockade cancelled the exacerbating effects of hIL-32β. We therefore conclude that IL-32 is closely associated with TNFα, and contributes to the exacerbation of TNFα-related inflammatory arthritis and colitis

Structure of the inhibitor complex of old yellow enzyme from Trypanosoma cruzi

The structures of old yellow enzyme from Trypanosoma cruzi which produces prostaglandin F2α from PGH2 have been determined in the presence or absence of menadione

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset

A history of mild shocks experienced by the regolith particles on hydrated asteroid Ryugu

Micrometeorites, a possible major source of Earth’s water, are thought to form from explosive dispersal of hydrated chondritic materials during impact events on their parental asteroids. However, this provenance and formation mechanism have yet to be directly confirmed using asteroid returned samples. Here, we report evidence of mild shock metamorphism in the surface particles of asteroid Ryugu based on electron microscopy. All particles are dominated by phyllosilicates but lack dehydration textures, which are indicative of shock-heating temperatures below ~500 °C. Microfault-like textures associated with extensively shock-deformed framboidal magnetites and a high-pressure polymorph of Fe–Cr–sulfide have been identified. These findings indicate that the average peak pressure was -2 GPa. The vast majority of ejecta formed during impact on Ryugu-like asteroids would be hydrated materials, larger than a millimetre, originating far from the impact point. These characteristics are inconsistent with current micrometeorite production models, and consequently, a new formation mechanism is required

ジセダイ パワー ディスク ザイリョウ オヨビ ダイヤモンド カンレン ザイリョウ ノ シガイセンコウ シエン カコウ ニ ヨル チョウ セイミツ カコウ ギジュツ ニ カンスル ケンキュウ

近年，電子機器類の高精度化・小型化が進み，従来の半導体素子材料として使用されてきたSiでは物性的に限界に近づきつつある．そこで，Siに比べてバンドギャップが大きく，機械的に非常に高硬度であり，なおかつ耐薬品性・放射線性に優れるSiCが，高温・高圧環境下，および宇宙領域における次世代半導体基板材料などへの応用が期待されている．また，物質中最高の硬度を有するダイヤモンドもその一例である．これまで，ダイヤモンドは工具への応用のみにとどまってきた．しかし，単結晶ダイヤモンドの成長技術の向上に伴い，今後はパワーデバイス用半導体基板としての応用にも期待されている．しかし，これらの次世代パワーデバイス用半導体材料は，非常に硬度が高く安定であることから，加工が困難であり，いまだその加工技術は確立されていない．単結晶ダイヤモンド以外のダイヤモンド関連材料としては，CVDダイヤモンドやPCDが非鉄金属材料や非金属材料の高精度切削工具として利用されており，今後は金型の接触部分に適用される耐摩耗材料としての利用されることが期待できる．金型を使用した加工では，金型の表面性状が製品に転写されるため，高精度に仕上げる必要がある．本研究では，紫外光支援加工を開発し，これらの硬脆材料に対する鏡面研磨技術として応用し，それぞれの加工メカニズムを明らかにするとともに，研磨に使用する定盤や条件が研磨特性に与える影響について調査した