HNF-1β過剰発現を呈する卵巣明細胞癌においてGSK-3βは新たなシグナル伝達経路を介在する

Deubiquitinase USP28 is a target gene of the transcription factor HNF1 homeobox β (HNF-1β), which promotes the survival of ovarian clear cell carcinoma (OCCC) cell lines. However, the pharmacological inhibition of HNF-1β can cause several adverse effects as it is abundantly expressed in numerous organ systems, including the kidney, liver, pancreas and digestive tract. Therefore, small interfering RNA (siRNA) screening was performed in the current study to identify other potential downstream targets of the HNF-1β-mediated pathway. The results revealed that glycogen synthase kinase-3β (GSK-3β) may be a potential downstream target affecting cell viability. To further clarify the effects of GSK-3β, two human OCCC cell lines, TOV-21G (HNF-1β overexpressing line) and ES2 (HNF-1β negative) were transfected with siRNA targeting GSK-3β or control vectors. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1β facilitated GSK-3β expression, resulting in the loss of phosphorylated nuclear factor-κB (p-NFκB) and the reduction of TOV-21G cell proliferation. The cell proliferation assay also revealed that GSK-3β inhibitors rescued the effects of HNF-1β silencing on cell viability in a dose-dependent manner. Furthermore, the GSK-3β inhibitor, AR-A014418, effectively inhibited tumor cell proliferation in a xenograft mouse model. In conclusion and to the best of our knowledge, the current study was the first to determine that GSK-3β is a target gene of HNF-1β. In addition, the results of the present study revealed the novel HNF-1β-GSK-3β-p-NFκB pathway, occurring in response to DNA damage. Targeting this pathway may therefore represent a putative, novel, anticancer strategy in patients with OCCC.博士（医学）・甲第785号・令和3年3月15日Copyright: © Kawaharaet al. This is an open access article distributed under theterms of CreativeCommons Attribution License(https://creativecommons.org/licenses/by-nc-nd/4.0/)

Methylation profiles of genes utilizing newly developed CpG island methylation microarray on colorectal cancer patients

Aberrant methylation of DNA has been shown to play an important role in a variety of human cancers, developmental disorders and aging. Hence, aberrant methylation patterns in genes can be a molecular marker for such conditions. Therefore, a reliable but uncomplicated method to detect DNA methylation is preferred, not merely for research purposes but for daily clinical practice. To achieve these aims, we have established a precise system to identify DNA methylation patterns based on an oligonucleotide microarray technology. Our microarray method has an advantage over conventional methods and is unique because it allows the precise measurement of the methylation patterns within a target region. Our simple signal detection system depends on using an avidin–biotinylated peroxidase complex and does not require an expensive laser scanner or hazardous radioisotope. In this study, we applied our technique to detect promoter methylation status of O(6)-methylguanine-DNA methyltransferase (MGMT) gene. Our easy-handling technology provided reproducible and precise measurement of methylated CpGs in MGMT promoter and, thus, our method may bring about a potential evolution in the handling of a variety of high-throughput DNA methylation analyses for clinical purposes

Method for determining the power-saved driving motion of manipulators by heuristic algorithms (In case of CP control)

This study proposes a method for suppressing the torques of the manipulators, with considering the effect of inertial forces in order to achieve the power-saved drive. The present study generates the trajectories, which here reveal time profiles of positions, velocities and accelerations of the entire path of the output point of manipulators. The trajectories of manipulators are introduced by determining both the initial position and motion curves for the entire path. This study expresses the motion curve as a polynomial and determines its coefficients. The initial pose and unknown coefficients are decided by a heuristic algorithm to achieve power-saved drive. As such problems have non-linearity and multi-peak solutions, it is difficult to find out the optimum one. Thus, this study uses a heuristic algorithm "SHA" to determine the appropriate motions of manipulators, because the heuristic algorithm is, as well known, an effective solution for such complicated problem. This study determines the optimal motions of the PUMA560 comprising spatial 3 degrees-of-freedom by the proposed method, and verifies its availability

Three topics of monopole dynamics in abelian projected QCD

Three topics about monopole dynamics after abelian projection are reported. The first is the new and detailed analyses of $SU(2)$ monopole action obtained after the block-spin transformation on the dual lattice. The $b=na(\beta)$ dependence for all couplings are well fitted with a universal curve. The distance dependence of the couplings is well reproduced by a massive propagator with the mass $m=0.8$ in unit of $b$. The second is the $SU(3)$ monopole action recently obtained. The third is new interesting gauges showing abelian and monopole dominances as in the maximally abelian gauge.Comment: Talk presented at LATTICE96(topology), 4 Pages, 7 eps figure

A Study on High School and Undergraduate Students’ Learning Motivation : A Case of Joint Management of the Educational Relationship between K Agricultural High School and A University for the “K Agricultural High School & A University Program"

This paper introduces the joint management of an educational relationship between K Agricultural High School and A University, and reports the program's effects to increase students' motivation for learning at both schools. In the program, first, the high school students presented the results of their project based learning, and the university students and university instructor gave comments. Next, the high school students received a lecture from the university instructor and a research report from the university student. Finally, the high school students, university students, and instructors attended a social gathering. An analysis of responses to the study questionnaire suggests that students’ motivation for learning increased at both schools, except the university students who have high motivation originally

Non-Gaussian Error Contribution to Likelihood Analysis of the Matter Power Spectrum

We study the sample variance of the matter power spectrum for the standard Lambda Cold Dark Matter universe. We use a total of 5000 cosmological N-body simulations to study in detail the distribution of best-fit cosmological parameters and the baryon acoustic peak positions. The obtained distribution is compared with the results from the Fisher matrix analysis with and without including non-Gaussian errors. For the Fisher matrix analysis, we compute the derivatives of the matter power spectrum with respect to cosmological parameters using directly full nonlinear simulations. We show that the non-Gaussian errors increase the unmarginalized errors by up to a factor 5 for k_{max}=0.4h/Mpc if there is only one free parameter provided other parameters are well determined by external information. On the other hand, for multi-parameter fitting, the impact of the non-Gaussian errors is significantly mitigated due to severe parameter degeneracies in the power spectrum. The distribution of the acoustic peak positions is well described by a Gaussian distribution, with its width being consistent with the statistical interval predicted from the Fisher matrix. We also examine systematic bias in the best-fit parameter due to the non-Gaussian errors. The bias is found to be smaller than the 1 sigma statistical error for both the cosmological parameters and the acoustic scale positions.Comment: 12 pages, 10 figures, accepted for publication in ApJ, minor change