Fundamental Parameters of the Milky Way Galaxy Based on VLBI astrometry

We present analyses to determine the fundamental parameters of the Galaxy based on VLBI astrometry of 52 Galactic maser sources obtained with VERA, VLBA and EVN. We model the Galaxy's structure with a set of parameters including the Galaxy center distance R_0, the angular rotation velocity at the LSR Omega_0, mean peculiar motion of the sources with respect to Galactic rotation (U_src, V_src, W_src), rotation-curve shape index, and the V component of the Solar peculiar motions V_sun. Based on a Markov chain Monte Carlo method, we find that the Galaxy center distance is constrained at a 5% level to be R_0 = 8.05 +/- 0.45 kpc, where the error bar includes both statistical and systematic errors. We also find that the two components of the source peculiar motion U_src and W_src are fairly small compared to the Galactic rotation velocity, being U_src = 1.0 +/- 1.5 km/s and W_src = -1.4 +/- 1.2 km/s. Also, the rotation curve shape is found to be basically flat between Galacto-centric radii of 4 and 13 kpc. On the other hand, we find a linear relation between V_src and V_sun as V_src = V_sun -19 (+/- 2) km/s, suggesting that the value of V_src is fully dependent on the adopted value of V_sun. Regarding the rotation speed in the vicinity of the Sun, we also find a strong correlation between Omega_0 and V_sun. We find that the angular velocity of the Sun, Omega_sun, which is defined as Omega_sun = Omega_0 + V_sun/R_0, can be well constrained with the best estimate of Omega_sun = 31.09 +/- 0.78 km/s/kpc. This corresponds to Theta_0 = 238 +/- 14 km/s if one adopts the above value of R_0 and recent determination of V_sun ~ 12 km/s.Comment: 14 pages, 6 figures, PASJ in pres

Activity Report of Industry-Academia Collaboration and Intellectual Property Management Section, Kawasaki Medical School－ the middle of 2021 fiscal year to the middle of 2022－

　産学連携知的財産管理室が2016年に発足して６年が経過し，業務は多岐にわたり活動が拡大してきた。それに伴い徐々に実用化案件や共同研究案件も増加しつつある。この１年間の特筆すべき点として，RNA 創薬に関する研究成果を基に川崎医科大学発のバイオベンチャー第１号が立ち上がり2022年３月から支援することとなった。また，肺癌治療におけるバイオマーカー測定の案件が実用化し技術導出された。その一方で発明届の数は減少しており，研究支援と同様に知的財産創出のリテラシーの向上も必要である。今後も業務の効率化・適正化を進め，他学との交流を推進し，シーズとニーズのマッチングの機会をできるだけ多く確保するように努力していきたい。　Six years have passed since the Industry-Academia Collaboration and Intellectual Property Management Section was established in 2016 and its works have expanded in a wide variety of areas. Along with this, the number of practically realized cases and collaboration researches is gradually increasing. The notable point in the past year is the launch of the first university bio- venture in Kawasaki Medical school based on the study results on RNA-based drug discovery, which has been supported from March 2022. In addition, the project of biomarker measurement in lung cancer treatment has been practically realized and the technology has been licensed-out. In contrast, the number of the invention notifications has been decreased year by year, and it is necessary to improve the literacy of intellectual property creation as well as research support. From now on, we will continue to improve the efficiency and optimization of our work, to promote exchanges with other universities, and to make efforts to secure as many opportunities as possible for matching seeds and needs

Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice

Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3−/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3−/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3−/− mice. Lipid metabolism disorders in Sik3−/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice

助産学生の学習到達度とその関連要因の分析

出版社版目的:助産学生の卒業時の学習到達度の把握と自己学習能力の観点から関連要因を分析することで、助産師教育を検討した。方法:対象者は看護専修学校2校の助産学生44名(有効回答率80.0%)で、研究協力の同意が得られた。測定用具は学習到達度自己評価票、日本語版SDLRS、一般性セルフエフィカシー尺度から構成した。学習到達度自己評価票は、ICMの「基本的助産業務に必須な能力」(1999年)を参考に113項目で構成し、452点滴点であった。調査回数は入学時と卒業時の2回/年とした。結果・考察:学習到達度自己評価票総合点の平均値が325.1点、学習到達度は71.9%であった。その内訳は知識項目が154.7点で学習到達度が69.1%、技術項目が170.5点で学習到達度が74.8%であり、技術項目が高かった。領域別学習到達度は、高い順に新生児のケア75.0%、分娩期のケア73.5%、産褥期のケア73.0%、妊娠期のケア69.1%であった。学習到達度の関連要因は、卒業時の自己決定型学習の準備性、卒業時の自己効力感、および分娩介助件数であった。(著者抄録

Low-dose radiation attenuates chemical mutagenesis in vivo - Cross adaptation -

The biological effects of low-dose radiation are not only of social concern but also of scientific interest. The radioadaptive response, which is defined as an increased radioresistance by prior exposure to low-dose radiation, has been extensively studied both in vitro and in vivo. Here we briefly review the radioadaptive response with respect to mutagenesis, survival rate, and carcinogenesis in vivo, and introduce our recent findings of cross adaptation in mouse thymic cells, that is, the suppressive effect of repeated low-dose radiation on mutation induction by the alkylating agent N-ethyl-N-nitrosourea

Role of Exposure Sequence in the Combined Effect of Ionizing Radiation and N-ethyl-N-nitrosourea in Murine T-cell Lymhomagenesis

Murine T-cell lymphomas (TL) can be reproducibly induced by ionizing radiation or chemical carcinogens. This animal model is considered useful in the search for characterization of genes involved in the development of human acute lymphoblastic leukemia. We have been studying this lymphoma model, which is induced by X-rays, carbon-ions or alkylating agents such as N-ethyl-N-nitrosourea (ENU). In the study of X-ray induced thymic lymphomas in B6C3F1 mice, we found a unique locus with a high frequency of loss of heterozygosity (LOH) (50%) in the centromeric region of chromosome 11 [1]. LOH at this locus was very rarely observed in ENU-induced or spontaneously developing T-cell lymphomas, suggesting that it was a radiation-associated molecular change. We also showed that Ikaros was mapped in this frequent LOH locus, suggesting Ikaros as a tumor suppressor gene. Ikaros is a transcription factor that plays a critical role in both lineage commitment and differentiation of lymphocytes. The mutation analysis of Ikaros in the X-ray- or ENU-induced lymphomas revealed that Ikaros mutation frequency and spectrum is carcinogen dependent. Mutation frequency in X-ray-induced TL was around 50%, while that in ENU-induced TL was 20%. Inactivation of Ikaros in X-ray-induced TL was caused by transcriptional silencing, unusual splicing, point mutation and small insertion, most of which were associated with LOH [2]. LOH at Ikaros locus was generated by intra-chromosomal deletion [3]. On the other hand, Ikaros inactivation in ENU-induced TLs was caused by only point mutations not accompanied with LOH [4]. Thus, the mutation of Ikaros was distinguished between X-rays-induced TL and ENU-induced one. Recently, we showed that TL induced in mismatch repair gene Mlh1-deficient mice harbored frequent frameshift mutations in mononucleotide sequence in Ikaros, suggesting Ikaros is also a mutational target in Mlh1-dificient mice [5]. Taken together, Ikaros could be inactivated by several mechanisms. Recently our interest is focused on the effect of combined exposure of radiation and chemical carcinogens. Since we are living in the environment with numerous natural and man-made radiation and chemicals, cancer development in human is considered as a result of interaction with these factors. But, the quantitative assessment and mechanistic understanding of combined effects of radiation and chemical carcinogens are still insufficient. The aim of this study is to elucidate the mode and mechanism of the combined effect of X-rays with ENU on mouse T-cell leukemogenesis. Beginning at 4- or 8-weeks of age, female B6C3F1 mice were exposed weekly to whole body X-irradiation (0.2 ? 2.0 Gy) for consecutive 4 weeks or were given ENU (50 ? 400 ppm) in drinking water for consecutive 4 weeks. The dose-response curve for X-ray- or ENU?induced lymphoma had threshold dose. Combined exposure was carried out by X-irradiation followed by ENU or by reverse sequence ENU followed by X-irradiation. The exposure of high dose X-rays followed by ENU resulted in a synergistic effect, while the effect was antagonistic at low or threshold dose of carcinogens. Thus, combined effect is dose dependent. When the order of exposure was reversed, i.e., ENU followed by X-rays, the mode of combined exposure was additive at any doses. Molecular changes such as LOH and Ikaros mutations in TL after X-irradiation followed by ENU were similar to those in ENU-induced TL. In contrast, TL induced by reverse treatment exhibited mutations, which were similar to those found in X-ray-induced TL. It is concluded that the mode of combined effect is dependent upon the dose and the treatment order of carcinogens. \n1. Shimada Y., M. Nishimura, S. Kakinuma, M. Okumoto, T. Shiroishi, K. H. Clifton, S. Wakana: Radiation-associated loss of heterozygosity at the Znfn1a1 (Ikaros) locus on chromosome 11 in murine thymic lymphomas. Radiat Res 2000;154:293-300.?2. Kakinuma S., M. Nishimura, S. Sasanuma, K. Mita, G. Suzuki, Y. Katsura, T. Sado, Y. Shimada: Spectrum of Znfn1a1 (Ikaros) inactivation and its association with loss of heterozygosity in radiogenic T-cell lymphomas in susceptible B6C3F1 mice. Radiat Res 2002;157:331-340.?3. Yoshida M. A., A. Nakata, M. Akiyama, S. Kakinuma, T. Sado, M. Nishimura, Y. Shimada: Distinct structural abnormalities of chromosomes 11 and 12 associated with loss of heterozygosity in X-ray-induced mouse thymic lymphomas. Cancer Genet Cytogenet 2007: in press.?4. Kakinuma S., M. Nishimura, A. Kubo, J. Y. Nagai, Y. Amasaki, H. J. Majima, T. Sado, Y. Shimada: Frequent retention of heterozygosity for point mutations in p53 and Ikaros in N-ethyl-N-nitrosourea-induced mouse thymic lymphomas. Mutat Res 2005;572:132-141.?5. Kakinuma S., Y. Kodama, Y. Amasaki, S. Yi, Y. Tokairin, M. Arai, M. Nishimura, M. Monobe, S. Kojima, Y. Shimada: Ikaros is a mutational target for lymphomagenesis in Mlh1-deficient mice. Oncogene 2007;26:2945-2949.NIRS-Bfs Internatinal Workshop on Research Applications of the Radiationbiology Archive