Shine-Dalgarno相互作用の進化

学位の種別:課程博士University of Tokyo(東京大学

CD160 serves as a negative regulator of NKT cells in acute hepatic injury

[EN] CD160 and BTLA both bind to herpes virus entry mediator. Although a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is also involved is unclear. By analyzing CD160−/− mice and mixed bone marrow chimeras, we show that CD160 is not essential for NKT cell development. However, CD160−/− mice exhibit severe liver injury after in vivo challenge with α-galactosylceramide (α-GalCer). Moreover, CD160−/− mice are more susceptible to Concanavalin A challenge, and display elevated serum AST and ALT levels, hyperactivation of NKT cells, and enhanced IFN-γ, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates α-GalCer-induced hepatic injury in CD160−/− mice, suggesting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data thus implicate CD160 as a co-inhibitory receptor that delivers antigen-dependent signals in NKT cells to dampen cytokine production during early innate immune activationSIWe thank the NIH Tetramer Core Facility for providing PBS 57 ligand loaded CD1d Tetramers. Further, we thank the staffs of Gyerim Experimental Animal Resource Center for animal care and technical assistance. K.-M. Lee was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future planning (NRF-2016M3A9B6948342, NRF- 2017R1A2B3004828, and NRF-2018M3A9D3079288). S.-J. Kim was supported by the Korea Health Industry Development Institute (KHIDI-HI14C2640) grant funded by Korea Government. S.-J. Ha was supported by a grant from the NRF (NRF- 2018R1A2A1A05076997). T.-J. Kim was additionally supported by a grant from the NRF (NRF-2016R1A6A3A04009698

Defective Localization With Impaired Tumor Cytotoxicity Contributes to the Immune Escape of NK Cells in Pancreatic Cancer Patients

Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL, PBMC, and autologous tumor cells from 80 enrolled resectable PDAC patients to comprehend the NK cell defects within PDAC. Extremely low frequencies of NK cells (<0.5%) were found within PDAC tumors, which was attributable not to the low expression of tumor chemokines, but to the lack of chemokine receptor, CXCR2. Forced expression of CXCR2 in patients' NK cells rendered them capable of trafficking into PDAC. Furthermore, NK cells exhibited impaired cell-mediated killing of autologous PDAC cells, primarily due to insufficient ligation of NKG2D and DNAM-1, and failed to proliferate within the hypoxic tumor microenvironment. Importantly, these defects could be overcome by ex-vivo stimulation of NK cells from such patients. Importantly, when the proliferative capacity of NK cells in vitro was used to stratify patients on the basis of cell expansion, patients whose NK cells proliferated <250-fold experienced significantly lower DFS and OS than those with ≥250-fold. Ex-vivo activation of NK cells restored tumor trafficking and reactivity, hence provided a therapeutic modality while their fold expansion could be a potentially significant prognostic indicator of OS and DFS in such patients

The Time-Dependent Effect in Ultra High-Performance Concrete According to the Curing Methods

Ultra-high-performance concrete (UHPC) is required to develop multifunctional concrete structures such as long-span bridges. During the construction of long-span bridges, girders exhibit significant differences in age because they use different curing days in the precast process. In this study, the performances of UHPC were compared when subjected to long-term storage under various conditions after 3-day steam curing. At 365 days, the compressive strength of steam curing is 197 MPa, moist is 191 MPa, and the air is 169 MPa. Based on these differences, prediction models were proposed for long-term performances. Furthermore, the development characteristics of compressive strength, modulus of elasticity (MOE), and flexural strength until 365 days of age were analyzed under air, moist, and steam conditions. Steam curing exhibited the highest level of strength development while air curing showed the lowest. Flexural strength showed no significant difference depending on age because steel fibers were mixed with UHPC; they significantly contributed to flexural performance. The results would contribute to recognizing differences in strength between members at sites where UHPC is applied and to managing high-quality structures constructed using precast members. These research results are expected to contribute to efficient member production and process management during the construction of large structures such as super-long-span bridges

Additional file 4: Table S1. of Simple adjustment of the sequence weight algorithm remarkably enhances PSI-BLAST performance

The number of searches which were not converged before each iteration of PSI-BLAST. (XLSX 9 kb

Electrical Characteristics of Ultra-High-Performance Concrete Containing Carbon-Based Materials

Recently, carbon materials with unique properties, such as high tensile strength and electrical conductivity, have been extensively investigated for the multi-functionalization of concrete. Previous studies mainly focused on improving the performance of normal-strength concrete using carbon nanomaterials, such as carbon nanotubes and graphene nanoplates. Therefore, this study analyzed the effect of carbon materials on ultra-high-performance concrete (UHPC) mixed with steel fibers, which has an outstanding mechanical performance. In addition, length effects were investigated for carbon fibers with nanometer, micrometer, and millimeter sizes. The influences of carbon materials on 120 MPa UHPC were investigated, including expanded graphite, a well-known superior conductivity material. Electrical conductivity, compressive strength, tensile strength, and electrical conductivity were analyzed experimentally. As a result, compressive strength tends to decrease as the concentrations of carbon materials increase, and chopped fiber has the best performance at 10.5 MPa in terms of tensile strength. Since the electrical conductivity of chopped fiber was observed to be significantly higher than that of other materials at 6.6 times, millimeter-sized fiber would be most suitable as a carbon material for concrete. This study could guide future research on the multi-functionalization of UHPC with carbon-based materials, including mechanical and electrical conductivity performances

Additional file 3: of Simple adjustment of the sequence weight algorithm remarkably enhances PSI-BLAST performance

The ascii pssm file made from MSA-B using PSI-BLASTexB with setting minimum block width as 13. (ASCII 5 kb