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131.
Fujimoto R Kinoshita Y Kawabe A Kinoshita T Takashima K Nordborg M Nasrallah ME Shimizu KK Kudoh H Kakutani T 《PLoS genetics》2008,4(4):e1000048
A central question in genomic imprinting is how a specific sequence is recognized as the target for epigenetic marking. In both mammals and plants, imprinted genes are often associated with tandem repeats and transposon-related sequences, but the role of these elements in epigenetic gene silencing remains elusive. FWA is an imprinted gene in Arabidopsis thaliana expressed specifically in the female gametophyte and endosperm. Tissue-specific and imprinted expression of FWA depends on DNA methylation in the FWA promoter, which is comprised of two direct repeats containing a sequence related to a SINE retroelement. Methylation of this element causes epigenetic silencing, but it is not known whether the methylation is targeted to the SINE-related sequence itself or the direct repeat structure is also necessary. Here we show that the repeat structure in the FWA promoter is highly diverse in species within the genus Arabidopsis. Four independent tandem repeat formation events were found in three closely related species. Another related species, A. halleri, did not have a tandem repeat in the FWA promoter. Unexpectedly, even in this species, FWA expression was imprinted and the FWA promoter was methylated. In addition, our expression analysis of FWA gene in vegetative tissues revealed high frequency of intra-specific variation in the expression level. In conclusion, we show that the tandem repeat structure is dispensable for the epigenetic silencing of the FWA gene. Rather, SINE-related sequence is sufficient for imprinting, vegetative silencing, and targeting of DNA methylation. Frequent independent tandem repeat formation events in the FWA promoter led us to propose that they may be a consequence, rather than cause, of the epigenetic control. The possible significance of epigenetic variation in reproductive strategies during evolution is also discussed. 相似文献
132.
Itoh T Ito Y Ohguchi K Ohyama M Iinuma M Otsuki Y Nozawa Y Akao Y 《Bioorganic & medicinal chemistry》2008,16(2):721-731
Eupalinin A, a natural phytoalexin included in Eupatorium chinense L., exhibited a marked inhibitory effect on cell growth in HL60 cells. The morphological aspects of eupalinin A-treated cells evaluated by Hoechst 33342 nuclear staining indicated cell death, only a small part of which showed a typical apoptosis with nuclear fragmentation and condensation. To determine what type of cell death is caused by eupalinin A, we examined the contribution of caspases, Bcl-2 family proteins, MAP kinase, and PI3K/Akt, and mitochondrial membrane potential to this cell death. As a result, most part of the cell death was not associated with apoptosis because of caspase independence and no death factor released from mitochondria. Electron microscopic study indicated a characteristic finding of autophagy such as the formation of autophagosomes. Furthermore, the level of microctubule-associated-protein light chain 3 (LC3) II protein and monodancylcanaverin (MDC) incorporation were gradually increased with reduction of mitochondrial membrane potential by the accumulation of intracellular ROS after eupalinin A treatment. From these results, we can conclude that eupalinin A-induced cell death was mainly due to autophagy, which was initiated by increased ROS, resulting in the perturbation of mitochondrial membrane potential. Since the class III PI3K inhibitor such as 3-MA or LY294002 did not inhibit the eupalinin A-induced type II programmed cell death (PCD II), it was suggested that the PCD II was executed by Beclin-1 independent pathway of damage-induced mitochondrial autophagy (mitophagy). 相似文献
133.
Takeshi Shimomura Tetsuji Itoh Touru Sumiya Fujio Mizukami Masatoshi Ono 《Enzyme and microbial technology》2009,45(6-7):443-448
Acetylcholine sensor is successfully prepared by using immobilized enzymes, i.e., acetylcholinesterase and choline oxidase within separate hybrid mesoporous silica membranes with 12 nm pore diameter (F127M). The measurement was based on the detection of hydrogen peroxide produced by two sequential enzyme reactions. The determination range and the response time are 6.0–800 μM and within approximately 3 min, respectively. The sensor is very stable compared to free enzymes and 80% of the initial response was maintained even after storage for 80 days. These results show that two enzymes are successfully immobilized and well stabilized, and at the same time, two sequential enzyme reactions efficiently proceed within the separate hybrid mesoporous membranes. Further, we studied the possible detection of organophosphorus pesticides in terms of the inhibition of acetylcholinesterase activity, i.e., the decrease of current response, and demonstrated that the nanomolar concentrations of pesticide (DZN-oxon) can be detected with our sensor. 相似文献
134.
Yoshiyuki Sato Yu Onozaki Tetsuya Sugimoto Hideki Kurihara Kaori Kamijo Chie Kadowaki Toshiaki Tsujino Akiko Watanabe Sachie Otsuki Morihiro Mitsuya Masato Iida Kyosuke Haze Takumitsu Machida Yoko Nakatsuru Hideya Komatani Hidehito Kotani Yoshikazu Iwasawa 《Bioorganic & medicinal chemistry letters》2009,19(16):4673-4678
A novel class of imidazopyridine derivatives was designed as PLK1 inhibitors. Extensive SAR studies supported by molecular modeling afforded a highly potent and selective compound 36. Compound 36 demonstrated good antitumor efficacy in xenograft nude rat model. 相似文献
135.
Shimamura T Shibata J Kurihara H Mita T Otsuki S Sagara T Hirai H Iwasawa Y 《Bioorganic & medicinal chemistry letters》2006,16(14):3751-3754
5-Pyrimidinyl-2-aminothiazole 1 was identified as an inhibitor of cyclin-dependent kinases (CDKs) by a screening of the Merck sample repository. The introduction of a methyl group at the C-5 or C-6 position on the pyrimidine ring, directed toward the gate keeper residue of CDK4 (Phe93), led to significant enhancement of selectivity for CDK4 over other CDKs. Compound 3 exhibited more than 300-fold selectivity for CDK4 over CDK1, 2, 5, 7, and 9. Subsequent improvements in aqueous solubility afforded compound 4, which is available for further in vivo studies and this compound inhibited pRb phosphorylation and BrdU incorporation in tumor models. 相似文献
136.
Naganawa A Matsui T Saito T Ima M Tatsumi T Yamamoto S Murota M Yamamoto H Maruyama T Ohuchida S Nakai H Kondo K Toda M 《Bioorganic & medicinal chemistry》2006,14(19):6628-6639
4-({2-[Isobutyl(phenylsulfonyl)amino]-5-(trifluoromethyl)phenoxy}methyl)benzoic acid (1) is a functional PGE2 antagonist selective for EP1 receptor subtype. Analogs of 1, in which the phenyl-sulfonyl moiety has been replaced with more hydrophilic heteroarylsulfonyl moieties, exhibited more optimized antagonist activity, while some of them showed in vivo antagonist activity. Structure-activity relationship (SAR) studies are also presented. 相似文献
137.
Takuya Ikenari Tatsuya Kawaguchi Rei Ota Miki Matsui Ryota Yoshida Tetsuji Mori 《The journal of histochemistry and cytochemistry》2021,69(9):597
Fluoro-Jade C (FJC) staining has been used to detect degenerating neurons in tissue sections. It is a simple and easy staining procedure and does not depend on the manner of cell death. In some experiments, double staining with FJC and fluorescent immunostaining (FI) is required to identify cell types. However, pretreatment for FJC staining contains some processes that are harsh to fluorophores, and the FI signal is greatly reduced. To overcome this issue, we improved the double staining protocol to acquire clear double-stained images by introducing the labeled streptavidin–biotin system. In addition, several studies indicate that FJC can label non-degenerating glial cells, including resting/reactive astrocytes and activated microglia. Moreover, our previous study indicated that degenerating mesenchymal cells were also labeled by FJC, but it is still unclear whether FJC can label degenerating glial cells. Acute encephalopathy model mice contained damaged astrocytes with clasmatodendrosis, and 6-aminonicotinamide-injected mice contained necrotic astrocytes and oligodendrocytes. Using our improved double staining protocol with FJC and FI, we detected FJC-labeled degenerating astrocytes and oligodendrocytes with pyknotic nuclei. These results indicate that FJC is not specific to degenerating neurons in some experimental conditions: 相似文献
138.
Aline Garcia Kozlowski Megmar Aparecida dos Santos Carneiro Márcia Alves Dias de Matos Sheila Araújo Teles Jo?o Alves Araújo Filho Koko Otsuki Ana Carolina Paulo Vicente Regina Maria Bringel Martins 《Memórias do Instituto Oswaldo Cruz》2014,109(1):118-121
Human T-cell lymphotropic virus (HTLV) may impact the clinical course of tuberculosis
(TB). Both infections are highly endemic in Brazil. The aim of this study was to
assess the prevalence of HTLV-1/2 in TB patients in Central-West Brazil and to
perform a genetic characterisation of the respective isolates. Of the 402 patients,
six (1.49%) were positive for anti-HTLV and five (1.24%; 95% confidence interval:
0.46-3.05) were infected with HTLV-1/2. Genetic characterisation demonstrated that
the four HTLV-1 isolates belonged to the Transcontinental subgroup A of the
Cosmopolitan subtype a and that the HTLV-2 isolate belonged to subtype a (HTLV-2a/c).
The prevalence of HTLV infection observed in this study is higher than that observed
in local blood donors and the HTLV-1 and 2 subtypes identified are consistent with
those circulating in Brazil. 相似文献
139.
140.
Many pathogens important for medicine, veterinary medicine or public health belong to the genera alphavirus and rubivirus within the family Togaviridae. 29 species of alphaviruses have been reported, and most of them are arboviruses. Chikungnya virus re-emerged in Kenya in 2004 and the epidemics spread to the Indian Ocean islands and many countries in South Asia, South-East Asia and Europe. On the other hand, rubella virus, a sole member of the genus rubivirus, is the causative agent of rubella and congenital rubella syndrome (CRS). Because human is only a natural host of the virus and effective live attenuated vaccines are available, immunization activities are strengthened globally to eliminate rubella and CRS, together with measles. 相似文献