A Novel Signaling Pathway Mediated by the Nuclear Targeting of C-Terminal Fragments of Mammalian Patched 1

Background: Patched 1 (Ptc1) is a polytopic receptor protein that is essential for growth and differentiation. Its extracellular domains accept its ligand, Sonic Hedgehog, while the function of its C-terminal intracellular domain is largely obscure. Principal Findings: In this study, we stably expressed human Ptc1 protein in HeLa cells and found that it is subjected to proteolytic cleavage at the C-terminus, resulting in the generation of soluble C-terminal fragments. These fragments accumulated in the nucleus, while the N-terminal region of Ptc1 remained in the cytoplasmic membrane fractions. Using an anti-Ptc1 C-terminal domain antibody, we provide conclusive evidence that C-terminal fragments of endogenous Ptc1 accumulate in the nucleus of C3H10T1/2 cells. Similar nuclear accumulation of endogenous C-terminal fragments was observed not only in C3H10T1/2 cells but also in mouse embryonic primary cells. Importantly, the C-terminal fragments of Ptc1 modulate transcriptional activity of Gli1. Conclusions: Although Ptc1 protein was originally thought to be restricted to cell membrane fractions, our findings sugges

2-クロロプロペンの接触水素化による化成品前駆体合成

Allyl chloride, which is a cross-linking agent for synthetic resins and a synthetic intermediate that is used as an alkylating agent for pharmaceuticals, is often utilized and synthesized at production sites related organochlorides. In the synthesis process of allyl chloride, however, 2-chloropropene (2-PEN) is produced as the by-product and that is a problem because it essentially has no practical use. In this study, it was investigated about the hydrogenation of 2-PEN to 2-chloropropane (2-PAN) and propylene, which are precursors for various chemical products. The commercially available palladium catalysts such as OleMax 201, OleMax 301, OleMax 600, and HyFlex 500 were used for 2-PEN hydrogenation. The maximum yield of 2-PAN (10.6 %) was detected at 348 K, P(H2) = 13.5 kPa and P(2-PEN) = 8.8 kPa, on OleMax 600 (0.5 g), while the maximum yield of propylene (26.0 %) was realized under the same reaction conditions, with the exception of using at P(H2) = 7.9 kPa on HyFlex 500 (0.5 g). The selective formation of propylene such as 8.9, 100, and 8.9 % for the conversion of 2-PEN, the selectivity of propylene, and the yield of propylene, respectively, was realized on OleMax 201. The selective formation of 2-PAN, however, was not observed on all catalysts. Palladium loading strongly influenced the catalytic activity, but had none on either the specific surface area, or basic and acidic properties.アリルクロライドは，医薬品のアルキル化剤や合成樹脂の架橋剤の原料として使用されるため，有機塩素化合物に関連する生産現場ではよく使用され，製造されている。しかし，このアクリルクロライドの製造過程で，用途の少ない2-クロロプロペン（2-PEN）が副生し，問題となっている。本研究では，2-PEN の有効利用を目的として，2-PENの接触水素化により，汎用性の高い化成品前駆体である2-クロロプロパン（2-PAN）とプロピレンの合成を検討した。また，触媒にはOleMax 201，OleMax 301，OleMax 600，HyFlex 500 などの市販のパラジウム触媒を用いた。反応温度348 KにてP(H2)＝13.5 kPaおよびP(2-PEN)＝8.8 kPaの反応条件下で， OleMax 600（0.5 g）触媒を用いたときに2-PANの収率（10.6 %）が最大となった。一方，P(H2)＝7.9 kPaとし，それ以外は同じ反応条件において，HyFlex 500（0.5 g）触媒を用いたときにプロピレンの収率（26.0 %）は最大となった。OleMax 201触媒を用いた場合，2-PENの転化率，プロピレンの選択性，およびプロピレンの収率が，それぞれ8.9，100，8.9であった。このことからOleMax 201触媒を用いることで，プロピレンが選択的に合成できることが明らかとなった。一方，2-PANを選択的に合成する触媒は現在のところ見つかってはいない。触媒活性にはパラジウムの担持量は強く影響したが，比表面積や塩基性および酸性などの物性は触媒活性には影響しなかった

Recent outcome on age and tissue dependence of radiation carcinogenesis in mice and rats

Radiation is a useful tool for disease diagnosis and therapy. On the other hand, a risk of subsequent malignant neoplasms several decades after receiving radiation is a serious public concern. In this study, we introduce our current program on the carcinogenic effect of early-life exposure to radiation using mouse and rat models. We here show that there exist susceptible age windows for radiation carcinogenesis in a tissue dependent manner. Perinatal period is the most susceptible for radiation-induction of both medulloblastomas and renal cell carcinomas. Irradiation at neonatal and infant age efficiently induces intestinal and liver tumors. Mammary cancers develop frequently at around pubertal exposure. Conversely, the incidence of lung cancers rather increases as a function of age-at-exposure. Underlying mechanisms include age dependent changes in the rate of clonal expansion and susceptibility to radiation-induced cell killing of the progenitor cells.The 3rd Asian Congress of Radiation Researc