19 research outputs found

    Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

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    Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

    Portal Vein Aneurysm in a Patient with Cirrhosis Type C Controlled by Direct-Acting Antiviral Treatment

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    Introduction: Portal vein aneurysm (PVA) is a rare saccular or fusiform portal vein dilatation. The management and optimal treatment of PVA remain unknown. Case Presentation: A 53-year-old man with hepatitis C virus (HCV) infection was diagnosed with PVA measuring 28 mm in diameter. Under observation, his liver fibrosis progressed, and the PVA diameter gradually increased to 52 mm. The patient was treated with elbasvir-grazoprevir for 12 weeks, and HCV disappeared. After achieving sustained virological response, liver fibrosis improved and the PVA progression ceased. Conclusion: HCV clearance by direct-acting antiviral treatment not only regressed liver fibrosis but may have also restrained the progression of PVA in a patient with cirrhosis type C and PVA

    Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors

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    The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors. Instead, single-cell molecular and functional analysis demonstrated that most fetal T-IPs expressed genes of and had the potential to develop into lymphoid as well as myeloid components of the immune system. Moreover, studies of embryos deficient in the transcriptional regulator RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic restriction to the T cell lineage or the migration of T-IPs

    有機溶媒中での加水分解酵素によるカルボン酸の光学分割に関する研究

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    京都大学0048新制・課程博士博士(工学)甲第5392号工博第1283号新制||工||902(附属図書館)UT51-93-F149京都大学大学院工学研究科工業化学専攻(主査)教授 田中 渥夫, 教授 内本 喜一朗, 教授 伊藤 嘉彦学位規則第4条第1項該当Doctor of EngineeringKyoto UniversityDFA

    Control of cell attachment through polyDNA hybridization.

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    Cell-cell interactions play vital roles in embryo development and in homeostasis maintenance. Such interactions must be stringently controlled for cell-based tissue engineering and regenerative medicine therapies, and methods for studying and controlling cell-cell interactions are being developed using both biomedical and engineering approaches. In this study, we prepared amphiphilic PEG-lipid polymers that were attached to polyDNA with specific sequences. Incubation of cells with the polyDNA-PEG-lipid conjugate transferred some of the polyDNA to the cells' surfaces. Similarly, polyDNA-PEG-lipid conjugate using polyDNA with a complementary sequence was introduced to the surfaces of other cells or to a substrate surface. Cell-cell or cell-substrate attachments were subsequently mediated via hybridization between the two complementary polyDNAs and monitored using fluorescence microscopy

    Measurement of radon in air using a radon-218Po calibration curve determined by an absorptive non-volatile liquid scintillator

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    This work reports a novel method for determining 222Rn (radon) in air using a radon-218Po calibration curve constructed by an absorbable non-volatile liquid scintillator (NVLS). The ability of this method to detect low natural concentrations of radon was confirmed from linear extrapolation of the curve between 500 and 8000 Bq/m3. The calibration curve was created from data obtained from measurements performed in a radon calibration chamber at the National Institute of Radiological Science (NIRS) by using the least-squares method. The line had high precision and stability, and the required detection time was less than that of 214Po. An absorptive NVLS was used to collect radon and was found to be highly advantageous for α-spectrometry liquid scintillation measurements. Variations of the Ostwald coefficient due to changes in temperature and humidity, which affect radon absorption, were investigated and discussed
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