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111.
Michio Nakamura Nadia Corp Mariko Fujimoto Shiho Fujita Shunkichi Hanamura Hitoshige Hayaki Kazuhiko Hosaka Michael A. Huffman Agumi Inaba Eiji Inoue Noriko Itoh Nobuyuki Kutsukake Mieko Kiyono-Fuse Takanori Kooriyama Linda F. Marchant Akiko Matsumoto-Oda Takahisa Matsusaka William C. McGrew John C. Mitani Hitonaru Nishie Koshi Norikoshi Tetsuya Sakamaki Masaki Shimada Linda A. Turner James V. Wakibara Koichiro Zamma 《Primates; journal of primatology》2013,54(2):171-182
We have analyzed the ranging patterns of the Mimikire group (M group) of chimpanzees in the Mahale Mountains National Park, Tanzania. During 16 years, the chimpanzees moved over a total area of 25.2 or 27.4 km2, as estimated by the grid-cell or minimum convex polygon (MCP) methods, respectively. Annually, the M group used an average of 18.4 km2, or approximately 70 %, of the total home-range area. The chimpanzees had used 80 % of their total home range after 5 years and 95 % after 11 years. M group chimpanzees were observed more than half of the time in areas that composed only 15 % of their total home range. Thus, they typically moved over limited areas, visiting other parts of their range only occasionally. On average, the chimpanzees used 7.6 km2 (in MCP) per month. Mean monthly range size was smallest at the end of the rainy season and largest at the end of the dry season, but there was much variability from year to year. The chimpanzees used many of the same areas every year when Saba comorensis fruits were abundant between August and January. In contrast, the chimpanzees used several different areas of their range in June. Here range overlap between years was relatively small. Over the 16 years of the study we found that the M group reduced their use of the northern part of their range and increased their frequency of visits to the eastern mountainous side of their home range. Changes in home-range size correlated positively with the number of adult females but not with the number of adult males. This finding does not support a prediction of the male-defended territory model proposed for some East African chimpanzee unit-groups. 相似文献
112.
113.
Masaki Unno Albert Ardèvol Carme Rovira Masao Ikeda-Saito 《The Journal of biological chemistry》2013,288(48):34443-34458
Heme oxygenase catalyzes the degradation of heme to biliverdin, iron, and carbon monoxide. Here, we present crystal structures of the substrate-free, Fe3+-biliverdin-bound, and biliverdin-bound forms of HmuO, a heme oxygenase from Corynebacterium diphtheriae, refined to 1.80, 1.90, and 1.85 Å resolution, respectively. In the substrate-free structure, the proximal and distal helices, which tightly bracket the substrate heme in the substrate-bound heme complex, move apart, and the proximal helix is partially unwound. These features are supported by the molecular dynamic simulations. The structure implies that the heme binding fixes the enzyme active site structure, including the water hydrogen bond network critical for heme degradation. The biliverdin groups assume the helical conformation and are located in the heme pocket in the crystal structures of the Fe3+-biliverdin-bound and the biliverdin-bound HmuO, prepared by in situ heme oxygenase reaction from the heme complex crystals. The proximal His serves as the Fe3+-biliverdin axial ligand in the former complex and forms a hydrogen bond through a bridging water molecule with the biliverdin pyrrole nitrogen atoms in the latter complex. In both structures, salt bridges between one of the biliverdin propionate groups and the Arg and Lys residues further stabilize biliverdin at the HmuO heme pocket. Additionally, the crystal structure of a mixture of two intermediates between the Fe3+-biliverdin and biliverdin complexes has been determined at 1.70 Å resolution, implying a possible route for iron exit. 相似文献
114.
115.
Masamitsu Konno Atsushi Hamabe Shinichiro Hasegawa Hisataka Ogawa Takahito Fukusumi Shimpei Nishikawa Katsuya Ohta Yoshihiro Kano Miyuki Ozaki Yuko Noguchi Daisuke Sakai Toshihiro Kudoh Koichi Kawamoto Hidetoshi Eguchi Taroh Satoh Masahiro Tanemura Hiroaki Nagano Yuichiro Doki Masaki Mori Hideshi Ishii 《Development, growth & differentiation》2013,55(3):309-318
Adipose tissue‐derived mesenchymal stem cells (ADSCs) are multipotent and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β‐cells, and hepatocytes. Compared with the extraction of other stem cells such as bone marrow‐derived mesenchymal stem cells (BMSCs), that of ADSCs requires minimally invasive techniques. In the field of regenerative medicine, the use of autologous cells is preferable to embryonic stem cells or induced pluripotent stem cells. Therefore, ADSCs are a useful resource for drug screening and regenerative medicine. Here we present the methods and mechanisms underlying the induction of multilineage cells from ADSCs. 相似文献
116.
Akiharu Kubo Aiko Shiohama Takashi Sasaki Kazuhiko Nakabayashi Hiroshi Kawasaki Toru Atsugi Showbu Sato Atsushi Shimizu Shuji Mikami Hideaki Tanizaki Masaki Uchiyama Tatsuo Maeda Taisuke Ito Jun-ichi Sakabe Toshio Heike Torayuki Okuyama Rika Kosaki Kenjiro Kosaki Jun Kudoh Kenichiro Hata Akihiro Umezawa Yoshiki Tokura Akira Ishiko Hironori Niizeki Kenji Kabashima Yoshihiko Mitsuhashi Masayuki Amagai 《American journal of human genetics》2013,93(5):945-956
“Nagashima-type” palmoplantar keratosis (NPPK) is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis characterized by well-demarcated diffuse hyperkeratosis with redness, expanding on to the dorsal surfaces of the palms and feet and the Achilles tendon area. Hyperkeratosis in NPPK is mild and nonprogressive, differentiating NPPK clinically from Mal de Meleda. We performed whole-exome and/or Sanger sequencing analyses of 13 unrelated NPPK individuals and identified biallelic putative loss-of-function mutations in SERPINB7, which encodes a cytoplasmic member of the serine protease inhibitor superfamily. We identified a major causative mutation of c.796C>T (p.Arg266∗) as a founder mutation in Japanese and Chinese populations. SERPINB7 was specifically present in the cytoplasm of the stratum granulosum and the stratum corneum (SC) of the epidermis. All of the identified mutants are predicted to cause premature termination upstream of the reactive site, which inhibits the proteases, suggesting a complete loss of the protease inhibitory activity of SERPINB7 in NPPK skin. On exposure of NPPK lesional skin to water, we observed a whitish spongy change in the SC, suggesting enhanced water permeation into the SC due to overactivation of proteases and a resultant loss of integrity of the SC structure. These findings provide an important framework for developing pathogenesis-based therapies for NPPK. 相似文献
117.
Youichi Kawakita Masaki Seto Tomohiro Ohashi Toshiya Tamura Tadashi Yusa Hiroshi Miki Hidehisa Iwata Hidenori Kamiguchi Toshimasa Tanaka Satoshi Sogabe Yoshikazu Ohta Tomoyasu Ishikawa 《Bioorganic & medicinal chemistry》2013,21(8):2250-2261
A novel 7,6 fused bicyclic scaffold, pyrimido[4,5-b]azepine was designed to fit into the ATP binding site of the HER2/EGFR proteins. The synthesis of this scaffold was accomplished by an intramolecular Claisen-type condensation. As the results of optimization lead us to 4-anilino and 6-functional groups, we discovered 6-substituted amide derivative 19b, which has a 1-benzothiophen-4-yloxy group attached to the 4-anilino group. An X-ray co-crystal structure of 19b with EGFR demonstrated that the N-1 and N-3 nitrogens of the pyrimido[4,5-b]azepine scaffold make hydrogen-bonding interactions with the main chain NH of Met793 and the side chain of Thr854 via a water-mediated hydrogen bond network, respectively. In addition, the NH proton at the 9-position makes an additional hydrogen bond with the carbonyl group of Met793, as we expected. Compound 19b revealed potent HER2/EGFR kinase (IC50: 24/36 nM) and BT474 cell growth (GI50: 18 nM) inhibitory activities based on its pseudo-irreversible (PI) profile. 相似文献
118.
Hirotaka Kashiwagi Yoshiyuki Ono Masateru Ohta Susumu Itoh Fumihiko Ichikawa Suguru Harada Satoshi Takeda Nobuo Sekiguchi Masaki Ishigai Tadakatsu Takahashi 《Bioorganic & medicinal chemistry》2013,21(7):1823-1833
In an extension of our study on gamma hydroxy carboxylic acid analogs, we explored a series of nonsecosteroidal vitamin D receptor (VDR) agonists in which 1,3-diol of 1,25(OH)2D3 had been replaced by aryl acetic acid. These analogs showed very potent activity in vitro compared with 1,25(OH)2D3. An X-ray analysis of 8d showed that the inserted phenyl ring well mimicked the folded methylene linker of the gamma hydroxy carboxylic acid moiety but the carboxylic acid of 8d interacted with VDR in a different manner from gamma hydroxy carboxylic acids. Through our in vivo screening in an osteoporosis rat model using immature rats, we identified a potent active vitamin D3 analog, compound 7e. In mature rats of the same model, compound 7e also showed good PK profiling and excellent ability to prevent bone mineral density loss without severe hypercalcemia. Our nonsecosteroidal VDR agonist 7e (CH5036249) could be a possible new drug candidate for treating osteoporosis in human. 相似文献
119.
Masaki Setoguchi Shin Iimura Yuuichi Sugimoto Yoshiyuki Yoneda Jun Chiba Toshiyuki Watanabe Fumihito Muro Yutaka Iigo Gensuke Takayama Mika Yokoyama Tomoe Taira Misato Aonuma Tohru Takashi Atsushi Nakayama Nobuo Machinaga 《Bioorganic & medicinal chemistry》2013,21(1):42-61
We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys. 相似文献
120.
Masaki Wakasugi Hiroaki Gouda Tomoyasu Hirose Akihiro Sugawara Tsuyoshi Yamamoto Kazuro Shiomi Toshiaki Sunazuka Satoshi Ōmura Shuichi Hirono 《Bioorganic & medicinal chemistry》2013,21(11):3214-3220
Human acidic mammalian chitinase (hAMCase) was recently shown to be involved in the development of asthma, suggesting a possible application for hAMCase inhibitors as novel therapeutic agents for asthma. We therefore initiated drug discovery research into hAMCase using a combination of in silico methodologies and a hAMCase assay system. We first selected 23 candidate hAMCase inhibitors from a database of four million compounds using a multistep screening system combining Tripos Topomer Search technology, a docking calculation and two-dimensional molecular similarity analysis. We then measured hAMCase inhibitory activity of the selected compounds and identified seven compounds with IC50 values ?100 μM. A model describing the binding modes of these hit compounds to hAMCase was constructed, and we discuss the structure–activity relationships of the compounds we identified, suggested by the model and the actual inhibitory activities of the compounds. 相似文献