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71.
Hideyuki Yoshida Caleb A. Lareau Ricardo N. Ramirez Samuel A. Rose Barbara Maier Aleksandra Wroblewska Fiona Desland Aleksey Chudnovskiy Arthur Mortha Claudia Dominguez Julie Tellier Edy Kim Dan Dwyer Susan Shinton Tsukasa Nabekura YiLin Qi Bingfei Yu Michelle Robinette Christophe Benoist 《Cell》2019,176(4):897-912.e20
72.
Keiji Uchiyama Hironori Miyata Masashi Yano Yoshitaka Yamaguchi Morikazu Imamura Naomi Muramatsu Nandita Rani Das Junji Chida Hideyuki Hara Suehiro Sakaguchi 《PloS one》2014,9(10)
Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp0/+ mice, compared with RML- and 22L-inoculated Prnp0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc. 相似文献
73.
Kambe T Maruyama T Nakai Y Yoshida H Oida H Maruyama T Abe N Nishiura A Nakai H Toda M 《Bioorganic & medicinal chemistry》2012,20(7):2235-2251
To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of γ-lactam prostaglandin E analogs bearing a 16-phenyl ω-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. 相似文献
74.
We have partially characterized root hydrotropism and its interaction with gravitropism in maize (Zea mays L.). Roots of Golden Cross Bantam 70, which require light for orthogravitropism, showed positive hydrotropism; bending upward when placed horizontally below a hydrostimulant (moist cheesecloth) in 85% relative humidity (RH) and in total darkness. However, the light-exposed roots of Golden Cross Bantam 70 or roots of a normal maize cultivar, Burpee Snow Cross, showed positive gravitropism under the same conditions; bending downward when placed horizontally below the hydrostimulant in 85% RH. Light-exposed roots of Golden Cross Bantam 70 placed at 70° below the horizontal plane responded positively hydrotropically, but gravitropism overcame the hydrotropism when the roots were placed at 45° below the horizontal. Roots placed vertically with the tip down in 85% RH bent to the side toward the hydrostimulant in both cultivars, and light conditions did not affect the response. Such vertical roots did not respond when the humidity was maintained near saturation. These results suggest that hydrotropic and gravitropic responses interact with one another depending on the intensity of one or both factors. Removal of the approximately 1.5 millimeter root tip blocked both hydrotropic and gravitropic responses in the two cultivars. However, removal of visible root tip mucilage did not affect hydrotropism or gravitropism in either cultivar. 相似文献
75.
Takeichiro Aso Mioko Matsuo Hideyuki Kiyohara Kenichi Taguchi Fumihide Rikimaru Mototsugu Shimokawa Yuichi Segawa Yuichiro Higaki Hirohito Umeno Tadashi Nakashima Muneyuki Masuda 《PloS one》2015,10(3)
Background
At our institute, a chemoradioselection strategy has been used to select patients for organ preservation on the basis of response to an initial 30–40 Gy concurrent chemoradiotherapy (CCRT). Patients with a favorable response (i.e., chemoradioselected; CRS) have demonstrated better outcomes than those with an unfavorable response (i.e., nonchemoradioselected; N-CRS). Successful targeting of molecules that attenuate the efficacy of chmoradioselection may improve results. Thus, the aim of this study was to evaluate the association of a novel cancer stem cell (CSC) marker, CD44 variant 9 (CD44v9), with cellular refractoriness to chemoradioselection in advanced head and neck squamous cell carcinoma (HNSCC).Materials and Methods
Through a medical chart search, 102 patients with advanced HNSCC treated with chemoradioselection from 1997 to 2008 were enrolled. According to our algorithm, 30 patients were CRC following induction CCRT and 72 patients were N-CRS. Using the conventional immunohistochemical technique, biopsy specimens and surgically removed tumor specimens were immunostained with the anti-CD44v9 specific antibodies.Results
The intrinsic expression levels of CD44v9 in the biopsy specimens did not correlate with the chemoradioselection and patient survival. However, in N-CRS patients, the CD44v9-positive group demonstrated significantly (P = 0.008) worse prognosis, than the CD44v9-negative group. Multivariate analyses demonstrated that among four candidate factors (T, N, response to CCRT, and CD44v9), CD44v9 positivity (HR: 3.145, 95% CI: 1.235–8.008, P = 0.0163) was significantly correlated with the poor prognosis, along with advanced N stage (HR: 3.525, 95% CI: 1.054–9.060, P = 0.0228). Furthermore, the survival rate of the CD44v9-induced group was significantly (P = 0.04) worse than the CD44v9-non-induced group.Conclusions
CCRT-induced CD44v9-expressing CSCs appear to be a major hurdle to chemoradioselection. CD44v9-targeting seems to be a promising strategy to enhance the efficacy of chemoradioselection and consequent organ preservation and survival. 相似文献76.
Kong F Abe J Takahashi K Matsuura H Yoshihara T Nabeta K 《Biochemical and biophysical research communications》2005,336(4):1150-1156
Theobroxide, a natural product, strongly stimulates the biosynthesis of jasmonic acid (JA) in Pharbitis nil. In this study, we investigated the accumulation of protein by the immunoblot analysis of lipoxygenase (LOX), allene oxide synthase (AOS), and allene oxide cyclase (AOC), key enzymes in JA biosynthesis, and how the endogenous levels of JA in P. nil are affected by theobroxide. The effect of JA on the accumulations of these proteins was monitored simultaneously. The results show that theobroxide treatment led to a high level accumulation of JA, which is due to high accumulations of LOX, AOS, and AOC proteins induced by theobroxide treatment both under short day (SD) and long day (LD) conditions. However, under SD conditions AOS and AOC proteins are not enhanced by JA treatment. Kinetic analysis of protein levels shows that a biphasic activation of AOC protein by theobroxide is displayed and the first activation of AOC protein together with elevated JA levels is observed within 30min after treatment. Meanwhile, AOS and LOX proteins are activated by theobroxide later than AOC protein, suggesting that AOC plays an essential role in the initial JA formation induced by theobroxide. Since theobroxide-increased JA levels also show a biphasic manner similar to AOC activation and AOS, LOX proteins are activated later than AOC, and thus we propose a positive JA feedback regulation. Interestingly, AOS protein, which is also the enzyme for the biosynthesis of 9,10-ketol-octadecadienoic acid (KODA, a flowering inducing factor), accumulates markedly due to the simultaneous involvement of theobroxide and SD conditions, suggesting that AOS probably plays a role in flower bud formation in P. nil. 相似文献
77.
Degradation of estrogens by Rhodococcus zopfii and Rhodococcus equi isolates from activated sludge in wastewater treatment plants 总被引:1,自引:0,他引:1
Yoshimoto T Nagai F Fujimoto J Watanabe K Mizukoshi H Makino T Kimura K Saino H Sawada H Omura H 《Applied and environmental microbiology》2004,70(9):5283-5289
We have isolated four strains of Rhodococcus which specifically degrade estrogens by using enrichment culture of activated sludge from wastewater treatment plants. Strain Y 50158, identified as Rhodococcus zopfii, completely and rapidly degraded 100 mg of 17beta-estradiol, estrone, estriol, and ethinyl estradiol/liter, as demonstrated by thin-layer chromatography and gas chromatography-mass spectrometry analyses. Strains Y 50155, Y 50156, and Y 50157, identified as Rhodococcus equi, showed degradation activities comparable with that of Y 50158. Using the random amplified polymorphism DNA fingerprinting test, these three strains were confirmed to have been derived from different sources. R. zopfii Y 50158, which showed the highest activity among these four strains, revealed that the strain selectively degraded 17beta-estradiol during jar fermentation, even when glucose was used as a readily utilizable carbon source in the culture medium. Measurement of estrogenic activities with human breast cancer-derived MVLN cells showed that these four strains each degraded 100 mg of 17beta-estradiol/liter to 1/100 of the specific activity level after 24 h. It is thus suggested that these strains degrade 17beta-estradiol into substances without estrogenic activity. 相似文献
78.
Screening and industrial application of unique microbial reactions involved in nucleic acid and lipid metabolisms 总被引:1,自引:0,他引:1
Ogawa J Soong CL Kishino S Li QS Horinouchi N Shimizu S 《Bioscience, biotechnology, and biochemistry》2006,70(3):574-582
Bioprocesses, which involve biocatalysts for the production of useful compounds, are expected to become a leading player in green chemistry. The first step in bioprocess development is screening for useful biological reactions in the immense number of microorganisms with infinite diversity and versatility. This review introduces some examples of bioprocess development that started from process design stemming from the discovery of unique metabolic processes, reactions, and enzymes in microbial nucleic acid and lipid metabolisms. 相似文献
79.
Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA 总被引:6,自引:0,他引:6
Takeshima H Suetake I Shimahara H Ura K Tate S Tajima S 《Journal of biochemistry》2006,139(3):503-515
In mammals, the resetting of DNA methylation patterns in early embryos and germ cells is crucial for development. De novo type DNA methyltransferases Dnmt3a and Dnmt3b are responsible for creating DNA methylation patterns during embryogenesis and in germ cells. Although their in vitro DNA methylation properties are similar, Dnmt3a and Dnmt3b methylate different genomic DNA regions in vivo. In the present study, we have examined the DNA methylation activity of Dnmt3a and Dnmt3b towards nucleosomes reconstituted from recombinant histones and DNAs, and compared it to that of the corresponding naked DNAs. Dnmt3a showed higher DNA methylation activity than Dnmt3b towards naked DNA and the naked part of nucleosomal DNA. On the other hand, Dnmt3a scarcely methylated the DNA within the nucleosome core region, while Dnmt3b significantly did, although the activity was low. We propose that the preferential DNA methylation activity of Dnmt3a towards the naked part of nucleosomal DNA and the significant methylation activity of Dnmt3b towards the nucleosome core region contribute to their distinct methylation of genomic DNA in vivo. 相似文献
80.
12-oxo-phytodienoic acid triggers expression of a distinct set of genes and plays a role in wound-induced gene expression in Arabidopsis 下载免费PDF全文