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排序方式: 共有473条查询结果,搜索用时 15 毫秒
71.
Takahashi A Imai Y Yamakoshi K Kuninaka S Ohtani N Yoshimoto S Hori S Tachibana M Anderton E Takeuchi T Shinkai Y Peters G Saya H Hara E 《Molecular cell》2012,45(1):123-131
Both the DNA damage response (DDR) and epigenetic mechanisms play key roles in the implementation of senescent phenotypes, but very little is known about how these two mechanisms are integrated to establish senescence-associated gene expression. Here we show that, in senescent cells, the DDR induces proteasomal degradation of G9a and GLP, major histone H3K9 mono- and dimethyltransferases, through Cdc14B- and p21(Waf1/Cip1)-dependent activation of APC/C(Cdh1) ubiquitin ligase, thereby causing a global decrease in H3K9 dimethylation, an epigenetic mark for euchromatic gene silencing. Interestingly, induction of IL-6 and IL-8, major players of the senescence-associated secretory phenotype (SASP), correlated with a decline of H3K9 dimethylation around the respective gene promoters and knockdown of Cdh1 abolished IL-6/IL-8 expression in senescent cells, suggesting that the APC/C(Cdh1)-G9a/GLP axis plays crucial roles in aspects of senescent phenotype. These findings establish a role for APC/C(Cdh1) and reveal how the DDR integrates with epigenetic processes to induce senescence-associated gene expression. 相似文献
72.
73.
The innate immune system constitutes the front line of host defense against pathogens. Toll-like receptors (TLRs) recognize
molecules derived from pathogens and play crucial roles in the innate immune system. Here, we provide evidence that the TLR-related
genes have come under natural selection pressure in the course of primate evolution. We compared the nucleotide sequences
of 16 TLR-related genes, including TLRs (TLR1–10), MYD88, TILAP, TICAM1, TICAM2, MD2, and CD14, among seven primate species. Analysis of the non-synonymous/synonymous substitution ratio revealed the presence of both
strictly conserved and rapidly evolving regions in the TLR-related genes. The genomic segments encoding the intracellular
Toll/interleukin 1 receptor domains, which exhibited lower rates of non-synonymous substitution, have undergone purifying
selection. In contrast, TLR4, which carried a high proportion of non-synonymous substitutions in the part of extracellular domain spanning 200 amino acids,
was found to have been the suggestive target of positive Darwinian selection in primate evolution. However, sequence analyses
from 25 primate species, including eight hominoids, six Old World monkeys, eight New World monkeys, and three prosimians,
showed no evidence that the pressure of positive Darwinian selection has shaped the pattern of sequence variations in TLR4 among New World monkeys and prosimians.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
74.
Gao Min-tian Makoto Hirata Michiteru Koide Hirokazu Takanashi Tadashi Hano 《Process Biochemistry》2004,39(12):1903-1907
An efficient process for producing l-lactic acid using an, EDF method is described. The results showed that intermittent EDF with continuous medium feed was the best one among the experiment methods employed. Comparing with the conventional EDF, intermittent EDF (seven on–off) with continuous medium feed indicated that the maximum value of o.d.660 was not increased, but productivity was 1.5 times higher. The yield increased by above 30% and glucose transport decreased to 1/10 (from 0.46 to 0.05). 相似文献
75.
Toshitsugu Kawata Kaoru Tenjou Chiyoko Tokimasa Tadashi Fujita Masato Kaku Akira Matsuki Shinya Kohno Keisuke Tsutsui Junji Ohtani Masahide Motokawa Mao Shigekawa Yuiko Tohma Kazuo Tanne 《Experimental Animals》2004,53(1):47-51
Alendronate, one of the bisphosphonates, is known to have an inhibitory effect on bone resorption. The purpose of this study was to investigate the effects of alendronate on ectopic bone graft resorption and to determine the optimal dose in the mouse. The grafted bone in the control group disappeared due to resorption by osteoclasts within 5 weeks. In the experimental groups, the area of bone tissue decreased by only 20-40% at 5 weeks post-operatively. At 8 and 9 weeks after surgery, the decreased area of bone structure was significantly less in all the 10(-4) M injected alendronate-immersed groups than in the 10(-4) M non-injected alendronate-immersed. At 9 weeks after surgery, the number of osteoclasts were significantly less in the 10(-4) M injected alendronate-treated groups than in the 10(-4) M non-injected alendronate-treated groups. These results suggest that alendronate inhibits resorption of ectopic bone graft at concentrations of 10(-4) and 10(-6) M. 相似文献
76.
We developed a method to measure the rupture forces between antibody and antigen by atomic force microscopy (AFM). Previous studies have reported that in the measurement of antibody–antigen interaction using AFM, the specific intermolecular forces are often obscured by nonspecific adhesive binding forces between antibody immobilized cantilever and substrate surfaces on which antigen or nonantigen are fixed. Here, we examined whether detergent and nonreactive protein, which have been widely used to reduce nonspecific background signals in ordinary immunoassay and immunoblotting, could reduce the nonspecific forces in the AFM measurement. The results showed that, in the presence of both nonreactive protein and detergent, the rupture forces between anti-ferritin antibodies immobilized on a tip of cantilever and ferritin (antigen) on the substrate could be successfully measured, distinguishing from nonspecific adhesive forces. In addition, we found that approach/retraction velocity of the AFM cantilever was also important in the reduction of nonspecific adhesion. These insights will contribute to the detection of specific molecules at nanometer scale region and the investigation of intermolecular interaction by the use of AFM. 相似文献
77.
Shu-ichi Kobayashi Tomas J Acosta Takahiro Ozawa Kanako Hayashi Bajram Berisha Masayuki Ohtani Dieter Schams Akio Miyamoto 《Biology of reproduction》2002,66(1):174-179
The newly formed corpus luteum (CL) develops rapidly and has the features of active vascularization and mitosis of steroidogenic cells. Such local mechanisms must be strictly regulated by the complex relationship between angiogenic growth factors and vasoactive peptides such as angiotensin (Ang) II, atrial natriuretic peptide (ANP), and endothelin (ET)-1. Thus, the objective of the present study was to determine 1) the changes in vasoactive peptides and progesterone (P) concentrations within the developing CL, along with the changes in concentration in ovarian venous plasma (OVP) and jugular venous plasma (JVP) in the cow, 2) the effects of CL exposure to vasoactive peptides on Ang II and P secretion, and 3) the expression of mRNA for ANP type C receptor in the bovine CL and endothelial cells (ETC) from bovine developing CL. A microdialysis system (MDS) was surgically implanted into multiple CL of six cows on Day 3 after a GnRH injection that induced superovulation, and a catheter was simultaneously inserted into the ovarian vein. The Ang II concentration in OVP was higher than that in JVP throughout the experiment, while the intraluteal release of Ang II was stable. During the experimental period, the concentrations of other vasoactive peptides (ANP and ET-1) showed no clear changes in plasma and were below detectable levels in the MDS perfusate. Exposure of CL to Ang II using the MDS stimulated P release, while exposure to ANP enhanced Ang II release within the developing CL. However, ET-1 had no effect on either P or Ang II release. The expression of mRNA for ANP type C receptor was mainly observed in early CL and ETC. The results suggest that the ET-Ang-ANP system in the preovulatory follicle switches to an Ang-ANP system to enhance both the angiogenesis and steroidogenesis that are actively occurring in developing CL. 相似文献
78.
79.
William Ba-Thein Satoko Inui Tohru Shimizu Tint Swe Sayera Banu Kaori Ohtani Misari Oe Naomi Sakurai Shinichi Nakamura Hideo Hayashi 《Microbiology and immunology》1997,41(8):629-631
The genomic structure of the pfoA-colA region in six theta-toxin-deficient strains of Clostridium perfringens was examined by Southern hybridization using the pfoR, pfoA, pbg, arcABDC and colA genes, encoding regulator for pfoA, theta-toxin, beta-galactosidase, arginine metabolism enzymes and kappa-toxin, respectively, as gene probes. It is suggested that the productivity of theta-toxin in these strains is diverse because of the multiple genetic backgrounds including single deletion of pfoA, large deletion of the pfoA-colA region and the putative point mutations. 相似文献
80.
Toshitsugu Kawata Chiyoko Tokimasa Tadashi Fujita Masato Kaku Keisuke Tsutsui Shinya Kohno Akira Matsuki Kaoru Tenjo Junji Ohtani Masahide Motokawa Takashi Kobayakawa Mao Shigekawa Kazuo Tanne 《Experimental Animals》2002,51(5):521-524
The time-dependent effects of daily dosing of IGF-I (1.21 mg/g) on the linear growth of the femur were investigated in mice. The femoral length and volume and the number of osteoclasts were significantly greater after IGF-I injection as compared to the non-injected control, suggesting that the IGF-I imbalance might cause a quick turnover cycle of the bone resulting in the altered femoral modeling. 相似文献