Quantitative description of urban landscape by analyzing topography in “openness” index a case study in Tokyo Yamanote Region

of topography and its effect to the formation of urban landscape, it is important to discuss not only about natural environment sustainability, but also socio-cultural identity in the area. The topography of Tokyo is generally clarified as two zones, the west side called “Yamanote” which is the highland eroded by small rivers and valleys, and the east side called “Shitamachi” which is the alluvial land. There are some differences in urban landscape and socio-economical phenomena between these two areas which are influenced by topographical characteristics. Especially Yamanote area, labyrinthine street networks are formed by narrow and curved valleys, green spaces are preserved in steep land, while each place has unique landscape. Usually, these characteristics are discussed in fuzzy and qualitative sense, but in this paper, we present these characteristics by quantitative methods and indexes. We specifically analyzed such topographical characteristics in Tokyo Yamanote area by “Openness” index where slope can be described in broader scale. Furthermore, we described two characteristics of built environment by Space Syntax theory for street network pattern and GIS data for land use property included green area. By layering these three characteristics, the uniquely of areas could be identified. This method might be important to be applied in actual planning

Ubiquitin chains in the Dsk2 UBL domain mediate Dsk2 stability and protein degradation in yeast

Ubiquitin-like (UBL)-ubiquitin-associated (UBA) proteins, including Dsk2 and Rad23, act as delivery factors that target polyubiquitinated substrates to the proteasome. We report here that the Dsk2 UBL domain is ubiquitinated in yeast cells and that Dsk2 ubiquitination of the UBL domain is involved in Dsk2 stability, depending on the Dsk2 UBA domain. Also, Dsk2 lacking ubiquitin chains impaired ubiquitin-dependent protein degradation and decreased the interaction of Dsk2 with polyubiquitinated proteins in cells. Moreover, Dsk2 ubiquitination affected ability to restore the temperature-sensitive growth defect of dsk2 Delta. These results indicate that ubiquitination in the UBL domain of Dsk2 has in vivo functions in the ubiquitin-proteasome pathway in yeast

Histone deacetylase inhibitor (SAHA) and repression of EZH2 synergistically inhibit proliferation of gallbladder carcinoma

医薬保健研究域医学系Polycomb group protein EZH2, frequently overexpressed in malignant tumors, is the catalytic subunit of polycomb repressive complex 2 (PRC2). PRC2 interacts with HDACs in transcriptional silencing and relates to tumor suppressor loss. We examined the expression of HDAC isoforms (HDAC 1 and 2) and EZH2, and evaluated the possible use of HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and EZH2 repressor for gallbladder carcinoma. We used 48 surgically resected gallbladders and cultures of human gallbladder epithelial cells (HGECs), gallbladder carcinoma (TGBC2TKB), and cholangiocarcinoma (HuCCT-1 and TFK-1) cell lines for examination. Immunohistochemically, EZH2 was overexpressed in gallbladder carcinoma, especially poorly differentiated carcinoma, but not in normal epithelium. In contrast, HDAC1/2 were expressed in both carcinoma and normal epithelium in vivo. This pattern was verified in cultured cells; EZH2 was highly expressed only in TGBC2TKB, whereas HDAC1/2 were expressed in HGECs and TGBC2TKB. Interestingly, SAHA treatment caused significant cell number decline in three carcinoma cells, and this effect was synergized with EZH2 siRNA treatment; however, HGECs were resistant to SAHA. In TGBC2TKB cells, the expression of EZH2 and HDAC1/2 were decreased by SAHA treatment, and p16INK4a, E-cadherin, and p21were simultaneously activated; however, no such findings were obtained in HGECs, suggesting that the effect of SAHA depends on the EZH2-mediated tumor suppressor loss. In conclusion, this study suggests a possible mechanism by which carcinoma cells but not normal cells are sensitive to SAHA and indicates the efficacy of this new anticancer agent in combination with EZH2 repression in gallbladder carcinoma. © 2009 Japanese Cancer Association

Local balance of transforming growth factor-β1 secreted from cholangiocarcinoma cells and stromal-derived factor-1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma

金沢大学大学院医学系研究科がん細胞学Tumor-stromal interactions are important for the progression of malignant tumors. The purpose of the present study was to examine interactions of cholangiocarcinoma (CC) cells and stromal fibroblasts with respect to stromal-derived factor-1 (SDF-1) and transforming growth factor (TGF)-β1. Two cell lines of CC (HuCCT-1 and CCKS-1) and WI-38 fibroblast cell line were used for cell culture, and 12 CC tissue specimens for immunohistochemical studies. Invasion of CC cells was increased significantly by the supernatant from fibroblast cultures, but not by the supernatant from fibroblasts cocultured with CC cells. Expression of SDF-1 in cultured fibroblasts was downregulated by TGF-β1 treatment, and coculture with CC cells and anti-TGF-β1 neutralizing antibody restored the decreased SDF-1 expression, suggesting that TGF-β1 secreted from CC cells might have reduced the expression of SDF-1 by fibroblasts and might have reduced the increased invasion of CC cells induced by the supernatant from fibroblasts. Immunohistochemical expression of TGF-β1 in CC cells was focal or negative and that of SDF-1 was evident in stromal fibroblasts at the invasive front of CC. In conclusion, local mutual influence of TGF-β1 secreted from carcinoma cells and SDF-1 expressed by stromal fibroblasts may be involved in invasion of CC cells. © 2006 Japanese Society of Pathology

Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis

金沢大学大学院医学系研究科がん細胞学Aim: Serum antinuclear antibodies (ANA) are occasionally noted in patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH. Methods: We compared clinicopathological features in patients with ANA-positive NASH (n = 35) and ANA-negative NASH (n = 36). Inflammatory cell profiles and the distribution of oxidative stress markers were also examined immunohistochemically. Results: ANA-positive NASH was significantly associated with female gender (P = 0.005), high degree of portal inflammation (P = 0.039), interface activity (P = 0.036) and hepatocellular ballooning (P = 0.0008). In addition, ANA of high titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (P = 0.02). The degree of steatosis wais rather mild in the high-titer ANA group(P = 0.01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in the portal area and hepatic lobules in both ANA-positive and ANA-negative groups. There was no difference in the distribution of oxidative stress markers between ANA-positive and ANA-negative groups. Conclusion: These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanism may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis. © 2007 The Japan Society of Hepatology

メドヴェージェフ兄弟による「原子力収容所Atomic Gulag」認識の舞台裏 : ジョレス&ロイ共著『回想Из Воспоминаний (Memoirs)1925-2010』によせて

I have long wanted to know how and why the Medvedev brothers were able to write their well-known works,such as The Rise and Fall of Lysenko (1969) by Zhores, or Let History Judge (1970) by Roy. These works were initially only distributed as samizdat copies among rather small dissident groups, during the former USSR era, and they seldom gave enough information sources. The brothers\u27 recent book; Memoirs 1925-2010[Iz Vospominnanii 1925-2010](2010) ; of which the Japanese version was published last November, includes the authorities and witnesses for their early works, which they were never able to disclose under the KGB suppressing system. The brothers also share with us a great deal of interesting information from that period, especially on unknown exchanges between Zhores & Roy Medvedev brothers and writers, editors, scientists and artists who were famous in 1960s and 1970s. Finally, I try to explain the background for the concept of`Atomic Gulag\u27, which they originally set out in their book ; Unknown Stalin (2001), in particular, I focus on who and what were the major influences on the twin brothers as they developed this concept

Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function

The class II α-isoform of phosphatidylinositol 3-kinase (PI3K-C2α) is localized in endosomes, the trans-Golgi network and clathrin-coated vesicles; however, its functional role is not well understood. Global or endothelial-cell-specific deficiency of PI3K-C2α resulted in embryonic lethality caused by defects in sprouting angiogenesis and vascular maturation. PI3K-C2α knockdown in endothelial cells resulted in a decrease in the number of PI3-phosphate-enriched endosomes, impaired endosomal trafficking, defective delivery of VE-cadherin to endothelial cell junctions and defective junction assembly. PI3K-C2α knockdown also impaired endothelial cell signaling, including vascular endothelial growth factor receptor internalization and endosomal RhoA activation. Together, the effects of PI3K-C2α knockdown led to defective endothelial cell migration, proliferation, tube formation and barrier integrity. Endothelial PI3K-C2α deficiency in vivo suppressed postischemic and tumor angiogenesis and diminished vascular barrier function with a greatly augmented susceptibility to anaphylaxis and a higher incidence of dissecting aortic aneurysm formation in response to angiotensin II infusion. Thus, PI3K-C2α has a crucial role in vascular formation and barrier integrity and represents a new therapeutic target for vascular disease.In Press / 2013-03-18公開予定