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91.
92.
Tyrosine Phosphorylation of the Pioneer Transcription Factor FoxA1 Promotes Activation of Estrogen Signaling 下载免费PDF全文
93.
Onda K Shiraki R Ogiyama T Yokoyama K Momose K Katayama N Orita M Yamaguchi T Furutani M Hamada N Takeuchi M Okada M Ohta M Tsukamoto S 《Bioorganic & medicinal chemistry》2008,16(23):10001-10012
As a result of the various N-bicyclo-5-chloro-1H-indole-2-carboxamide derivatives with a hydroxy moiety synthesized in an effort to discover novel glycogen phosphorylase (GP) inhibitors, 5-chloro-N-(5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-indole-2-carboxamide (5b) was found to have potent inhibitory activity. The introduction of fluorine atoms both at a position adjacent to the hydroxy group and in the central benzene moiety lead to the optically active derivative 5-chloro-N-[(5R)-1,3,6,6-tetrafluoro-5-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl]-1H-indole-2-carboxamide (25e(alpha), which was the most potent compound in this series (IC(50)=0.020microM). This compound inhibited glucagon-induced glucose output in cultured primary hepatocytes with an IC(50) value of 0.69microM, and showed oral hypoglycemic activity in diabetic db/db mice at 10mg/kg. Compound 25e(alpha) also had an excellent pharmacokinetic profile, with high oral bioavailability and a long plasma half-life, in male SD rats. The binding mode of 25e(alpha) to this molecule and the role of fluorine atoms in that binding were speculated in an enzyme docking study. 相似文献
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Jun Suzuki Katsumi Yamaguchi Masaki Kajikawa Kenji Ichiyanagi Noritaka Adachi Hideki Koyama Shunichi Takeda Norihiro Okada 《PLoS genetics》2009,5(4)
Long interspersed elements (LINEs) are transposable elements that proliferate within eukaryotic genomes, having a large impact on eukaryotic genome evolution. LINEs mobilize via a process called retrotransposition. Although the role of the LINE-encoded protein(s) in retrotransposition has been extensively investigated, the participation of host-encoded factors in retrotransposition remains unclear. To address this issue, we examined retrotransposition frequencies of two structurally different LINEs—zebrafish ZfL2-2 and human L1—in knockout chicken DT40 cell lines deficient in genes involved in the non-homologous end-joining (NHEJ) repair of DNA and in human HeLa cells treated with a drug that inhibits NHEJ. Deficiencies of NHEJ proteins decreased retrotransposition frequencies of both LINEs in these cells, suggesting that NHEJ is involved in LINE retrotransposition. More precise characterization of ZfL2-2 insertions in DT40 cells permitted us to consider the possibility of dual roles for NHEJ in LINE retrotransposition, namely to ensure efficient integration of LINEs and to restrict their full-length formation. 相似文献
97.
Shoichi Kubota Yasunori Fukumoto Kenichi Ishibashi Shuhei Soeda Sho Kubota Ryuzaburo Yuki Yuji Nakayama Kazumasa Aoyama Noritaka Yamaguchi Naoto Yamaguchi 《The Journal of biological chemistry》2014,289(9):5730-5746
Mimosine is an effective cell synchronization reagent used for arresting cells in late G1 phase. However, the mechanism underlying mimosine-induced G1 cell cycle arrest remains unclear. Using highly synchronous cell populations, we show here that mimosine blocks S phase entry through ATM activation. HeLa S3 cells are exposed to thymidine for 15 h, released for 9 h by washing out the thymidine, and subsequently treated with 1 mm mimosine for a further 15 h (thymidine → mimosine). In contrast to thymidine-induced S phase arrest, mimosine treatment synchronizes >90% of cells at the G1-S phase boundary by inhibiting the transition of the prereplication complex to the preinitiation complex. Mimosine treatment activates ataxia telangiectasia mutated (ATM)/ataxia telangiectasia and Rad3-related (ATR)-mediated checkpoint signaling without inducing DNA damage. Inhibition of ATM activity is found to induce mimosine-arrested cells to enter S phase. In addition, ATM activation by mimosine treatment is mediated by reactive oxygen species (ROS). These results suggest that, upon mimosine treatment, ATM blocks S phase entry in response to ROS, which prevents replication fork stalling-induced DNA damage. 相似文献
98.
Toshitsugu Fukumaru Hiroshi Awata Noritaka Hamma Toshiaki Komatsu 《Bioscience, biotechnology, and biochemistry》2013,77(2):519-527
The synthesis of novel acetylenic ketone compounds and anti-inflammatory and antimicrobial activities are herein described. 相似文献
99.
Masayuki Nakamichi Fumiaki Cho Tetsuhiro Minami 《Primates; journal of primatology》1990,31(2):213-224
This study documents age-related changes in the interactions of wild-born cynomolgus macaque mothers and their infants living
in individual cages during the first 14 weeks of infant life. Body contact between mother and infant, maternal holding, and
infant sucking were found to decrease, and the mothers showed an increased frequency of aggression toward their infants with
age. These results were broadly similar to those reported for mother-infant interactions in other macaques living in social
groups. Nevertheless, a clear difference between the present cynomolgus macaques and other macaques in social groups was apparent.
The cynomolgus macaque mothers tended to permit their infants to move about freely without displaying maternal protectiveness
such as restraint or retrieval, unlike other macaque mothers in social groups. Such maternal behaviors might derive from the
experience of living in individual cages for many years and the relative safety of living in individual cages. The lack of
maternal restraint and retrieval could be responsible for the observed sex differences in behavior: male infants moved more
actively, and broke, and made contact with their mothers more frequently than did female infants. Moreover, mothers of female
infants held and groomed them more frequently and were less aggressive toward them. 相似文献
100.
M Hara-Yokoyama M Kukimoto-Niino K Terasawa S Harumiya KA Podyma-Inoue N Hino K Sakamoto S Itoh N Hashii Y Hiruta N Kawasaki C Mishima-Tsumagari Y Kaitsu T Matsumoto M Wakiyama M Shirouzu T Kasama H Takayanagi N Utsunomiya-Tate K Takatsu T Katada Y Hirabayashi S Yokoyama M Yanagishita 《Structure (London, England : 1993)》2012,20(9):1585-1595
The leukocyte cell-surface antigen CD38 is the major nicotinamide adenide dinucleotide glycohydrolase in mammals, and its ectoenzyme activity is involved in calcium mobilization. CD38 is also a raft-dependent signaling molecule. CD38 forms a tetramer on the cell surface, but the structural basis and the functional significance of tetramerization have remained unexplored. We identified the interfaces contributing to the homophilic interaction of mouse CD38 by site-specific crosslinking on the cell surface with an expanded genetic code, based on a crystallographic analysis. A combination of the three interfaces enables CD38 to tetramerize: one interface involving the juxtamembrane α-helix is responsible for the formation of the core dimer, which is further dimerized via the other two interfaces. This dimerization of dimers is required for the catalytic activity and the localization of CD38 in membrane rafts. The glycosylation prevents further self-association of the tetramer. Accordingly, the tetrameric interaction underlies the multifaceted actions of CD38. 相似文献