A Genetic Variant in the IL-17 Promoter Is Functionally Associated with Acute Graft-Versus-Host Disease after Unrelated Bone Marrow Transplantation

Interleukin IL-17 is a proinflammatory cytokine that has been implicated in the pathogenesis of various autoimmune diseases. The single nucleotide polymorphism (SNP), rs2275913, in the promoter region of the IL-17 gene is associated with susceptibility to ulcerative colitis. When we examined the impact of rs2275913 in a cohort consisting of 438 pairs of patients and their unrelated donors transplanted through the Japan Marrow Donor Program, the donor IL-17 197A allele was found to be associated with a higher risk of acute graft-versus-host disease (GVHD; hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.00 to 2.13; P = 0.05). Next, we investigated the functional relevance of the rs2275913 SNP. In vitro stimulated T cells from healthy individuals possessing the 197A allele produced significantly more IL-17 than those without the 197A allele. In a gene reporter assay, the 197A allele construct induced higher luciferase activity than the 197G allele, and the difference was higher in the presence of T cell receptor activation and was abrogated by cyclosporine treatment. Moreover, the 197A allele displayed a higher affinity for the nuclear factor activated T cells (NFAT), a critical transcription factor involved in IL-17 regulation. These findings substantiate the functional relevance of the rs2275913 polymorphism and indicate that the higher IL-17 secretion by individuals with the 197A allele likely accounts for their increased risk for acute GVHD and certain autoimmune diseases

Metalorganic chemical vapor deposition of β-FeSi2 on β-FeSi2 seed crystals formed on Si substrates

We have fabricated a β-FeSi2 film by metalorganic chemical vapor deposition on a Si(001) substrate with β-FeSi2 seed crystals grown by molecular beam epitaxy, and investigated the crystallinity, surface morphology and temperature dependence of photoresponse properties of the β-FeSi2 film. The surface of the grown β-FeSi2 film was atomically flat, and step-and-terrace structure was clearly observed. Multi-domain structure of β-FeSi2 whose average size was approximately 200 nm however was revealed. The photoresponse was obtained in an infrared light region (~ 0.95 eV) at temperatures below 200 K. The external quantum efficiency reached a maximum, being as large as 25% at 100 K when a bias voltage was 2.0 V

A novel keratin 5 mutation in an African family with epidermolysis bullosa simplex Iidicates the Importance of the amino acid located at the boundary site between the H1 and coil 1A domains

No abstractThis work was supported in part by Grant-in-Aid for Research Activity Start-up (to S. S.; 23890006) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by “Research on Measures for Intractable Diseases” Project: matching fund subsidy (H23-028) from the Ministry of Health, Labour and Welfare.http://www.medicaljournals.sehb201

Comprehensive study of liposome-assisted synthesis of membrane proteins using a reconstituted cell-free translation system

Membrane proteins play pivotal roles in cellular processes and are key targets for drug discovery. However, the reliable synthesis and folding of membrane proteins are significant problems that need to be addressed owing to their extremely high hydrophobic properties, which promote irreversible aggregation in hydrophilic conditions. Previous reports have suggested that protein aggregation could be prevented by including exogenous liposomes in cell-free translation processes. Systematic studies that identify which membrane proteins can be rescued from irreversible aggregation during translation by liposomes would be valuable in terms of understanding the effects of liposomes and developing applications for membrane protein engineering in the context of pharmaceutical science and nanodevice development. Therefore, we performed a comprehensive study to evaluate the effects of liposomes on 85 aggregation-prone membrane proteins from Escherichia coli by using a reconstituted, chemically defined cell-free translation system. Statistical analyses revealed that the presence of liposomes increased the solubility of >90% of the studied membrane proteins, and ultimately improved the yields of the synthesized proteins. Bioinformatics analyses revealed significant correlations between the liposome effect and the physicochemical properties of the membrane proteins