HAPPEN TO BE FASHIONABLE? : NEW PRACTICE CREATION THROUGH THE SEQUENCE OF MULTIPLE ACTORS

In contrast to previous research, this paper illustrates a process in which institutional entrepreneurs play less significant roles in creating a new practice. We drew on a historical case study that deals with the emergence of a new practice of emphasizing fashionable design of a type of clothing known as meisen. In the historical case study, multiple actors played distinctive and essential roles, which, as a whole, led to the creation of a new practice.

Na+-Cl-共輸送体を介したクロライド輸送はアルドステロン投与ラットの血圧上昇と腎障害に関与する

広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Alkylator-Induced DNA Excision Repair in Human Leukemia CCRF-CEM Cells In Vitro, Measured Using the Single-Cell Gel Electrophoresis (Comet) Assay

The capacity to repair DNA damage is an important factor that affects the therapeutic outcome in cancer treatment. To clarify the cellular repair response, we investigated the kinetics of DNA excision repair initiated by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in human leukemia CCRF-CEM cells at an exponential growth phase in vitro. Using the alkaline single-cell gel electrophoresis (comet) assay, we quantitated the repair kinetics as the amount of DNA single-strand breaks that were generated from the incision and were diminished by the rejoining in the repair process. CEM cells could initiate DNA excision repair in response to BCNU by starting an incision reaction. However, the incision capacity came to a plateau at a concentration of 80 to 1003M or after an incubation time of 90 to 120 minutes. When the cells were pulsed with 403M BCNU, the maximal incision occurred at the end of the incubation period, and the repair process was completed within 4 hours.When cells were treated with 1003M BCNU, the incised DNA was not rejoined at 4 hours, suggesting that the repair was not completed. Higher concentrations might surpass the cellular capacity for repair and would be associated with increased cell death. Evaluation of the repair process may provide a clue for therapeutic strategies to improve clinical efficacy if accelerated DNA repair is responsible for the drug resistance

UCN-01 (7-hydroxystaurosporine) inhibits DNA repair and increases cytotoxicity in normal lymphocytes and chronic lymphocytic leukemia lymphocytes.

Elevated DNA repair processes represent resistance mechanisms to the treatment of malignancies with alkylating agents. Recently, the cell cycle checkpoint abrogator, UCN-01, was reported to inhibit nucleotide excision repair in cell-free systems. We hypothesized that if UCN-01 was combined with DNA-damaging agents, UCN-01 might inhibit the damage repair processes, thereby enhancing cytotoxicity in quiescent cells. Here, we investigated the effect of UCN-01 on DNA repair and viability of quiescent normal lymphocytes and chronic lymphocytic leukemia lymphocytes treated with UV or the cyclophosphamide prodrug 4-hydroperoxycyclophosphamide (4-HC). DNA damage repair kinetics were determined as DNA single strand breaks by the alkaline single cell gel electrophoresis (comet) assay and by [3H]thymidine incorporation. Pretreatment with UCN-01 inhibited DNA repair initiated by UV or 4-HC in normal lymphocytes as well as chronic lymphocytic leukemia lymphocytes in a concentration-dependent manner at clinically relevant levels (50-300 nM). This inhibition was demonstrated by the decreases in incision capability, DNA resynthesis, and in rejoining, suggesting that UCN-01 inhibits the multiple sites of the repair processes. The higher UCN-01 concentration (300 nM) maximized the inhibitory effects and enhanced the UV- or 4-HC-induced cytotoxicity, as determined by annexin V binding or Hoechst 33342 staining. This enhancement was not obtained by the lower concentrations that incompletely inhibited the repair, suggesting the close association between the inhibition of the repair and the enhancement of the cytotoxicity. Our findings suggest that UCN-01 may be a good candidate for combination strategies of cancer treatment

Open inflation in the landscape

Open inflation scenario is attracting a renewed interest in the context of string landscape. Since there are a large number of metastable de Sitter vacua in string landscape, tunneling transitions to lower metastable vacua through the bubble nucleation occur quite naturally. Although the deviation of Omega_0 from unity is small by the observational bound, we argue that the effect of this small deviation on the large angle CMB anisotropies can be significant for tensor-type perturbation in open inflation scenario. We consider the situation in which there is a large hierarchy between the energy scale of the quantum tunneling and that of the slow-roll inflation in the nucleated bubble. If the potential just after tunneling is steep enough, a rapid-roll phase appears before the slow-roll inflation. In this case the power spectrum is basically determined by the Hubble rate during the slow-roll inflation. If such rapid-roll phase is absent, the power spectrum keeps the memory of the high energy density there in the large angular components. The amplitude of large angular components can be enhanced due to the effects of the wall fluctuation mode if the bubble wall tension is small. Therefore, one can construct some models in which the deviation of Omega_0 from unity is large enough to produce measurable effects. We also consider a more general class of models, where the false vacuum decay may occur due to Hawking-Moss tunneling, as well as the models involving more than one scalar field. We discuss scalar perturbations in these models and point out that a large set of such models is already ruled out by observational data, unless there was a very long stage of slow-roll inflation after the tunneling. These results show that observational data allow us to test various assumptions concerning the structure of the string theory potentials and the duration of the last stage of inflation.Comment: 14 pages, 11 figures, v2:minor corrections and a reference added, v3:accepted for publication in PR

Recombinant γY278H Fibrinogen Showed Normal Secretion from CHO Cells, but a Corresponding Heterozygous Patient Showed Hypofibrinogenemia

ArticleInternational journal of molecular sciences. 22(10): 5218(2021)journal articl

A new, simple method for quantifying gemcitabine triphosphate in cancer cells using isocratic high-performance liquid chromatography

A deoxycytidine analog, gemcitabine (dFdC), is effective for treating solid tumors and hematologic malignancies. After being transported into cancer cells, dFdC is phosphorylated to dFdC triphosphate (dFdCTP), which is subsequently incorporated into the DNA strand, thereby inhibiting DNA synthesis. Intracellular dFdCTP is the critical determinant for dFdC cytotoxicity, so therapeutic drug monitoring or in vitro testing of the capability of cancer cells to accumulate dFdCTP may be informative for optimizing dFdC administration. We have developed a new isocratic-elution HPLC method for quantifying dFdCTP in cancer cells. Samples (500 μl) were eluted isocratically using 0.06 M Na2HPO4 (pH = 6.9) containing 20% acetonitrile, at a constant flow rate of 0.7 ml/min and at ambient temperature. Separation was performed using an anion-exchange column, TSK gel DEAE-2SW (250 mm x 4.6 mm inside diameter, particle size 5 μl, TOSOH Corp.), and monitored at 254 nm. The standard curve was linear with low within-day and inter-day variability. The lower detection limit (20 pmol) was as sensitive as that of the previous gradient-elution method. dFdCTP was well separated from other nucleoside triphosphates. The method could measure dFdCTP in cultured or primary leukemic cells treated in vitro with dFdC. The method was also applicable to simultaneous determination of dFdCTP and cytarabine triphosphate, the results of which demonstrated the ara-CTP production augmented by the dFdC pretreatment. Thus, our isocratic HPLC assay method will be of great use because of its sensitivity and simplicity as well as its applicability to biological materials

Methanol bioeconomy: promotion of rice crop yield in paddy fields with microbial cells prepared from natural gas‐derived C 1 compound

微生物やその細胞壁成分の葉面散布による酒米の増収に成功 --メタノールを原料に生産した微生物製剤を出穂後1度の散布で--. 京都大学プレスリリース. 2020-12-11.Methylotrophs, which can utilize methanol as a sole carbon source, are promising microorganisms to be exploited in a methanol‐based bioeconomy, in which a variety of useful compounds are biotechnologically produced from natural gas‐derived methanol. Pink‐pigmented facultative methylotrophs (PPFMs) are common plant phyllospheric bacteria and are known to enhance seedling growth and total biomass of various plants. However, improvement of crop yield by inoculation of PPFMs at the field level has not been well investigated. We herein describe improvement of crop yield of several rice cultivars by foliar spraying of PPFMs. After selection of PPFM strains and rice cultivars by the in vitro seedling growth test, we further conducted paddy field experiments. The crop yield of the sake‐brewing rice Oryza sativa cultivar Hakutsurunishiki was reproducibly improved in a commercial paddy field for over a 5‐year period. A one‐time foliar spray of PPFM cells (living or killed) or a cell wall polysaccharide fraction, after the heading date, acted in the phyllosphere and effectively improved crop yield. Our results show that the established process with PPFMs is feasible for improvement of food production in the methanol bioeconomy