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21.
Amada H Sekiguchi Y Ono N Matsunaga Y Koami T Asanuma H Shiozawa F Endo M Ikeda A Aoki M Fujimoto N Wada R Sato M 《Bioorganic & medicinal chemistry letters》2012,22(5):2024-2029
A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-β-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC(50)=8.2nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC(50)=32nM). 相似文献
22.
Yasuyuki Fujii Hidenori OhtakeNaoya Ono Toshifumi HaraTakanobu Sakurai Syuya TakahashiTetsuo Takayama Yoshiki FukasawaFumiyasu Shiozawa Narutoshi TsukaharaTakehiro Hirayama Yasuyuki IgarashiRyo Goitsuka 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(4):600-606
Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking via type-1 S1P receptor (S1P1) and participates in many pathological conditions. We developed a novel type S1P1-selective antagonist, TASP0251078, which is structurally unrelated to S1P. This competitive antagonist inhibited binding of S1P to S1P1 resulting in reduced signaling downstream of S1P1, including GTPγS-binding and cAMP formation. TASP0251078 also inhibited S1P-induced cellular responses such as chemotaxis and receptor-internalization. Furthermore, when administered in vivo, TASP0251078 induced lymphopenia in blood, which is different from previously reported effects of other S1P1-antagonists. In a mouse contact hypersensitivity model, TASP0251078 effectively suppressed ear swelling, leukocyte infiltration, and hyperplasia. These findings provide the chemical evidence that S1P1 antagonism is responsible for lymphocyte sequestration from the blood, and suggest that the effect of S1P1 agonists on lymphocyte sequestration results from their functional antagonism. 相似文献
23.
Yosuke Tanaka Keisuke Satoh Takayuki Takebe Satoshi Shiozawa 《Journal of experimental marine biology and ecology》2008,354(1):56-64
RNA/DNA ratio is a useful and reliable indicator of the nutritional status of fish larvae and juveniles. In order to assess the nutritional status of field-caught larval Pacific bluefin tuna Thunnus orientalis (Temminck et Schlegel), starvation experiments of hatchery-reared larvae were conducted and changes in the RNA/DNA ratio of fed and starved larvae were analyzed. Starvation experiments were conducted every 3 days after first feeding. The survival rate of Pacific bluefin tuna larvae ranged 10-50% after 1 day of starved conditions and growth retardation was observed immediately. These results suggest that Pacific bluefin tuna larvae have a very low tolerance to starvation. The RNA/DNA ratios of fed larvae were approximately 2.0-4.0. On the other hand, the value of starved larvae significantly decreased to 1.0-3.0. The nutritional status of 3 cohorts of field-caught tuna larvae collected in the northwestern Pacific Ocean was examined based on the value of the RNA/DNA ratio of the 1 day starved larvae. 4.35-25.77% of the cohorts were regarded as the “starving condition”, which was negatively correlated to the ambient prey densities. These findings suggest that the nutritional condition of larval Pacific bluefin tuna was influenced by the ambient prey density, and starvation itself and starvation-induced predation could greatly contribute to mortality in the larval period of Pacific bluefin tuna. 相似文献
24.
Karina Keller Marques da Costa Flaiban Kledir Anderson H. Spohr Luciano de Souza Malanski Walfrido Kühl Svoboda Marcos M. Shiozawa Carmen Lúcia S. Hilst Lucas Moraes Aguiar Gabriela Ludwig Fernando C. Passos Italmar Teodorico Navarro Mara Regina Stipp Balarin Júlio Augusto Naylor Lisbôa 《International journal of primatology》2008,29(5):1375-1382
We evaluated blood samples obtained from 80 free-ranging healthy capuchins (Cebus cay and C. nigritus) to establish hematological reference values and to assess the influence of sex and age on them. We caught the monkeys in
the Paraná River region of Southern Brazil via manual or automatic traps. We anesthetized them intramuscularly with 3.6 mg/kg
tiletamine/zolazepam hydrochlorides. After physical examinations, we divided the sample according to sex and age: 26 females
(13 adults and 13 juveniles) and 54 males (27 adults and 27 juveniles). We collected blood and determined hematological values
via traditional published methods. We analyzed data via 2-way ANOVA to test the effect of sex, age, and interactions between
the 2 factors. The packed-cell volume was higher in adult males and the numbers of white blood cells and lymphocytes were
higher in juveniles. There is no other significant difference. 相似文献
25.
Shima Okada Naruhiro Shiozawa Yoshihisa Fujiwara Yasushi Yasuda Masaaki Makikawa Takeo Iida 《Journal of thermal biology》2008
To clarify the effect of cold stimulation during slow-wave sleep (SWS) on the sleep cycle, we conducted a sleep experiment. Five healthy males slept on a bedding system we developed to make the inside of bedding cooler. When the subject was sleeping deeply in the second and fourth SWS, the system cooled their bedding. When the subject's sleep condition shifted toward arousal, the cold air was stopped. As a result, all subjects’ sleep stage shifted to light sleep and reached arousal. After stopping stimulation, they immediately returned to the SWS at the first stimulation. But at the second stimulation, the sleep state did not return to the SWS. 相似文献
26.
Empirical tests for ecological exchangeability 总被引:2,自引:0,他引:2
Russell B. Rader Mark C. Belk Dennis K. Shiozawa Keith A. Crandall 《Animal Conservation》2005,8(3):239-247
27.
Rieko Oyama Fusako Kito Marimu Sakumoto Kumiko Shiozawa Shunichi Toki Akihiko Yoshida Akira Kawai Tadashi Kondo 《In vitro cellular & developmental biology. Animal》2018,54(3):257-263
Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal malignancy requiring novel therapeutic approaches to improve clinical outcome. Patient-derived cancer cell lines are an essential tool for investigating molecular mechanisms underlying cancer initiation and development; however, there is a lack of patient-derived cell lines of UPS available for research. The objective of this study was to develop a patient-derived cell model of UPS. A cell line designated NCC-UPS2-C1 was established from the primary tumor tissue of an 84-yr-old female patient with UPS. The short tandem repeat pattern of NCC-UPS2-C1 cells was identical to that of the original tumor and distinct from that of any other cell lines deposited in public cell banks. NCC-UPS2-C1 cells were maintained as a monolayer culture for over 80 passages during 30 mo and exhibited spindle-like morphology, continuous growth, and ability for spheroid formation and invasion. Proteomic profiling using mass spectrometry and functional treemap analysis revealed that the original tumor and the derived NCC-UPS2-C1 cells had similar but distinct protein expression patterns. Our results indicate that a novel UPS cell line was successfully established and could be used to study UPS development and effects of anti-cancer drugs. However, the revealed difference between proteomes of the original tumor and NCC-UPS2-C1 cells should be further investigated to determine the appropriate applications of this cell line in UPS research. 相似文献
28.
Domain architecture of vasohibins required for their chaperone‐dependent unconventional extracellular release 下载免费PDF全文
Tetsuya Kadonosono Wanaporn Yimchuen Takuya Tsubaki Tadashi Shiozawa Yasuhiro Suzuki Takahiro Kuchimaru Yasufumi Sato Shinae Kizaka‐Kondoh 《Protein science : a publication of the Protein Society》2017,26(3):452-463
Vasohibins (VASH1 and VASH2) are recently identified regulators of angiogenesis and cancer cell functions. They are secreted proteins without any classical secretion signal sequences, and are thought to be secreted instead via an unconventional protein secretion (UPS) pathway in a small vasohibin‐binding protein (SVBP)‐dependent manner. However, the precise mechanism of SVBP‐dependent UPS is poorly understood. In this study, we identified a novel UPS regulatory system in which essential domain architecture (VASH‐PS) of VASHs, comprising regions VASH191–180 and VASH280–169, regulate the cytosolic punctate structure formation in the absence of SVBP. We also demonstrate that SVBP form a complex with VASH1 through the VASH1274–282 (SIa), VASH1139‐144 (SIb), and VASH1133–137 (SIc), leading to the dispersion in the cytosol and extracellular release of VASH1. The amino acid sequences of VASH‐SIa and VASH‐PS, containing SIb and SIc, are highly conserved among VASH family members in vertebrates, suggesting that SVBP‐dependent UPS may be common within the VASH family. This novel UPS regulatory system may open up new avenues for understanding fundamental protein secretion in vertebrates. 相似文献
29.
30.
Koichiro Yamada Tomonori Tsukahara Kazuhisa Yoshino Katsuhiko Kojima Hideyuki Agawa Yuki Yamashita Yuji Amano Mariko Hatta Yasunori Matsuzaki Naoki Kurotori Keiko Wakui Yoshimitsu Fukushima Ryosuke Osada Tanri Shiozawa Kazuo Sakashita Kenichi Koike Satoru Kumaki Nobuyuki Tanaka Toshikazu Takeshita 《Retrovirology》2009,6(1):1-9