Th17細胞及びILC2誘導機構の解明

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 清野 宏, 東京大学教授 森屋 恭爾, 東京大学特任准教授 岡本 一男, 東京大学准教授 秋山 泰身, 東京大学講師 上羽 悟史University of Tokyo(東京大学

Reconstruction of putative DNA virus from endogenous rice tungro bacilliform virus-like sequences in the rice genome: implications for integration and evolution

BACKGROUND: Plant genomes contain various kinds of repetitive sequences such as transposable elements, microsatellites, tandem repeats and virus-like sequences. Most of them, with the exception of virus-like sequences, do not allow us to trace their origins nor to follow the process of their integration into the host genome. Recent discoveries of virus-like sequences in plant genomes led us to set the objective of elucidating the origin of the repetitive sequences. Endogenous rice tungro bacilliform virus (RTBV)-like sequences (ERTBVs) have been found throughout the rice genome. Here, we reconstructed putative virus structures from RTBV-like sequences in the rice genome and characterized to understand evolutionary implication, integration manner and involvements of endogenous virus segments in the corresponding disease response. RESULTS: We have collected ERTBVs from the rice genomes. They contain rearranged structures and no intact ORFs. The identified ERTBV segments were shown to be phylogenetically divided into three clusters. For each phylogenetic cluster, we were able to make a consensus alignment for a circular virus-like structure carrying two complete ORFs. Comparisons of DNA and amino acid sequences suggested the closely relationship between ERTBV and RTBV. The Oryza AA-genome species vary in the ERTBV copy number. The species carrying low-copy-number of ERTBV segments have been reported to be extremely susceptible to RTBV. The DNA methylation state of the ERTBV sequences was correlated with their copy number in the genome. CONCLUSIONS: These ERTBV segments are unlikely to have functional potential as a virus. However, these sequences facilitate to establish putative virus that provided information underlying virus integration and evolutionary relationship with existing virus. Comparison of ERTBV among the Oryza AA-genome species allowed us to speculate a possible role of endogenous virus segments against its related disease

Detection of Nε-(hexanoyl)lysine in the tropomyosin 1 protein in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric cancer cells

Nε-(Hexanoyl)lysine, formed by the reaction of lysine with n-6 lipid hydroperoxide, is a lipid peroxidation marker during the initial stage of oxidative stress. The aim of the present study is to indentify Nε-(hexanoyl)lysine-modified proteins in neoplastic transformed gastric mucosal cells by N-methyl-N'-nitro-N-nitrosoguanidine, and to compare the levels of these proteins between gastric mucosal cells and normal gastric cells. Much greater fluorescence of 2-[6-(4'-hydroxy)phenoxyl-3H-xanthen-3-on-9-yl]benzoic acid, an index of the intracellular levels of reactive oxygen species, was observed for gastric mucosal cells compared to normal gastric cells. Nε-(Hexanoyl)lysine-modified proteins were detected by SDS-PAGE or two-dimensional electrophoresis and Western blotting using anti-Nε-(hexanoyl)lysine polyclonal antibody, and a protein band of between 30–40 kDa was clearly increased in gastric mucosal cells compared to normal gastric cells. Two Nε-(hexanoyl)lysine-modified protein spots in gastric mucosal cells were identified as the tropomyosin 1 protein by mass spectrometry using a MASCOT search. The existence of Nε-(hexanoyl)lysine modification in tropomyosin 1 was confirmed by Western blotting of SDS-PAGE-separated or two-dimensional electrophoresis-separated proteins as well as by the immunoprecipitation with anti-tropomyosin 1 antibody. These data indicate that Nε-(hexanoyl)lysine modification of tropomyosin 1 may be related to neoplastic transformation by N-methyl-N'-nitro-N-nitrosoguanidine in gastric epithelial cells

An invasive adenocarcinoma of the accessory parotid gland: a rare example developing from a low-grade cribriform cystadenocarcinoma?

Low-grade cribriform cystadenocarcinoma (LGCCA) is a rare tumor of the salivary gland that exhibits clinically indolent behavior. In this paper, we present a case of invasive adenocarcinoma of the accessory parotid gland in a young male that exhibited histology suggestive of an association of LGCCA. A 27-year-old man presented with a subcutaneous tumor in his left cheek. The tumor was separated from the parotid gland and located on the masseter muscle. The tumor was resected, and the postoperative histological diagnosis was adenocarcinoma, not otherwise specified (ANOS). The tumor exhibited papillary-cystic and cribriform proliferation of the duct epithelium and obvious stromal infiltration. Some tumor nests were rimmed by myoepithelium positive for smooth muscle actin, p63, and cytokeratin 14, indicating the presence of intraductal components of the tumor. Tumor cells exhibited mild nuclear atypia, and some of them presented an apocrine-like appearance and had cytoplasmic PAS-positive/diastase-resistant granules and hemosiderin. Other cells had foamy cytoplasm with microvacuoles. Immunohistochemistry revealed that the almost all of the tumor cells were strongly positive for S-100. These histological findings suggest the possibility that ANOS might arise secondarily from LGCCA. This is an interesting case regarding the association between ANOS and LGCCA in oncogenesis

Stromal micropapillary pattern predominant lung adenocarcinoma - a report of two cases

Generally, adenocarcinomas with micropapillary pattern, featuring small papillary tufts lacking a central fibrovascular core, are thought to have poor prognosis. This pattern has been described in various organs. However, tumor cells with micropapillary pattern of lung adenocarcinoma are more often seen to float within alveolar spaces (aerogenous micropapillary pattern, AMP) than in fibrotic stroma like other organs (stromal micropapillary pattern, SMP) and SMP predominant lung adenocarcinoma (SMPPLA) has not been well described yet. We presented two cases of SMPPLA which were found in the last four years. Both the cases showed more than 50% of SMP in the tumor area. The majority of the stromal micropapillary clusters expressed MUC1 and epithelial membrane antigen along the outer surface of cell membrane. On the other hand, connective tissues surrounding stromal micropapillary clusters showed no reactivity for epithelial markers (thyroid transcription factor-1 and cytokeratin) or endothelial marker (D2-40 and CD34). It means clusters of SMP do not exist within air space or lymphatic or vessel lumens. The tumors with SMP often presented lymphatic permeation and vessel invasion, and intriguingly, one of the two cases showed metastasis to the mediastinal lymph node. Additionally, both the cases showed EGFR point mutations of exon 21. These results suggest that SMPPLA might be associated with poor prognosis and effective for EGFR tyrosine kinase inhibitors

Synthesis of (+)-boronolide and (+)-deacetylboronolide using Pd-catalyzed carbonylation and lactonization

(+)-Boronolide and (+)-deacetylboronolide were synthesized using Pd-catalyzed CO insertion and lactonization as the key step. As to the C-13 NMR data of (+)-deacetylboronolide, the assignment at C-6 position should be revised.ArticleTETRAHEDRON LETTERS. 55(17):2822-2824 (2014)journal articl

Tumor suppressor REIC/Dkk-3 interacts with the dynein light chain, Tctex-1

Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. HuH-7 hepatoma-derived cells are widely used as the only cell-based HCV replication system for HCV research, including drug assays. Recently, using different hepatoma Li23-derived cells, we developed an HCV drug assay system (ORL8), in which the genome-length HCV RNA (O strain of genotype 1b) encoding renilla luciferase replicates efficiently. In this study, using the HuH-7-derived OR6 assay system that we developed previously and the ORL8 assay system, we evaluated 26 anti-HCV reagents, which other groups had reported as anti-HCV candidates using HuH-7-derived assay systems other than ORB. The results revealed that more than half of the reagents showed different anti-HCV activities from those in the previous studies, and that anti-HCV activities evaluated by the ORB and ORL8 assays were also frequently different. In further evaluation using the HuH-7-derived AH1R assay system, which was developed using the AH1 strain of genotype 1b, several reagents showed different anti-HCV activities in comparison with those evaluated by the OR6 and ORL8 assays. These results suggest that the different activities of anti-HCV reagents are caused by the differences in cell lines or HCV strains used for the development of assay systems. Therefore, we conclude that plural HCV assay systems developed using different cell lines or HCV strains are required for the objective evaluation of anti-HCV reagents

Demographic and Clinical Characteristics of Patients with Severe Asthma in the Asian Pacific Region : data from the International Severe Asthma Registry (ISAR)

Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Search for effective Lorentz and CPT violation using ZEUS data

Lorentz and CPT symmetry in the quark sector of the Standard Model are studied in the context of an effective field theory using ZEUS e±p data. Symmetry-violating effects can lead to time-dependent oscillations of otherwise time-independent observables, including scattering cross sections. An analysis using five years of inclusive neutral-current deep inelastic scattering events corresponding to an integrated HERA luminosity of 372 pb-1 at s=318 GeV has been performed. No evidence for oscillations in sidereal time has been observed within statistical and systematic uncertainties. Constraints, most for the first time, are placed on 42 coefficients parametrizing dominant CPT-even dimension-four and CPT-odd dimension-five spin-independent modifications to the propagation and interaction of light quarks