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151.
Kohno T Ichikawa H Totoki Y Yasuda K Hiramoto M Nammo T Sakamoto H Tsuta K Furuta K Shimada Y Iwakawa R Ogiwara H Oike T Enari M Schetter AJ Okayama H Haugen A Skaug V Chiku S Yamanaka I Arai Y Watanabe S Sekine I Ogawa S Harris CC Tsuda H Yoshida T Yokota J Shibata T 《Nature medicine》2012,18(3):375-377
152.
Nomura M Yumoto K Shinozaki T Isogai S Takano Y Murakami K 《Bioorganic & medicinal chemistry letters》2012,22(1):334-338
A series of novel cyclic amine-substituted benzoic acid derivatives were synthesized and evaluated for their PPARα agonist activity. Strucure-activity relationship studies led to the identification of (S)-3-[3-[2-(4-chlorophenyl)-4-methylthyazole-5-carboxamido]piperidin-1-yl]benzoic acid (S)-4f (KRP-105) as a potent and high subtype-selective human PPARα agonist. (S)-4f showed excellent PK profile and oral administration of (S)-4f to high-fat diet dogs effectively lowered triglycerides. 相似文献
153.
Letícia Maria Zanphorlin Mariana Abrahão Bueno de Morais José Alberto Diogo Mariane Noronha Domingues Flávio Henrique Moreira de Souza Roberto Ruller Mario Tyago Murakami 《Biotechnology and bioengineering》2019,116(4):734-744
Rational design is an important tool for sculpting functional and stability properties of proteins and its potential can be much magnified when combined with in vitro and natural evolutionary diversity. Herein, we report the structure-guided design of a xylose-releasing exo-β-1,4-xylanase from an inactive member of glycoside hydrolase family 43 (GH43). Structural analysis revealed a nonconserved substitution (Lys247) that results in the disruption of the hydrogen bond network that supports catalysis. The mutation of this residue to a conserved serine restored the catalytic activity and crystal structure elucidation of the mutant confirmed the recovery of the proper orientation of the catalytically relevant histidine. Interestingly, the tailored enzyme can cleave both xylooligosaccharides and xylan, releasing xylose as the main product, being the first xylose-releasing exo-β-1,4-xylanase reported in the GH43 family. This enzyme presents a unique active-site topology when compared with closely related β-xylosidases, which is the absence of a hydrophobic barrier at the positive-subsite region, allowing the accommodation of long substrates. Therefore, the combination of rational design for catalytic activation along with naturally occurring differences in the substrate binding interface led to the discovery of a novel activity within the GH43 family. In addition, these results demonstrate the importance of solvation of the β-propeller hollow for GH43 catalytic function and expand our mechanistic understanding about the diverse modes of action of GH43 members, a key and polyspecific carbohydrate-active enzyme family abundant in most plant cell-wall-degrading microorganisms. 相似文献
154.
Daisuke Kawahara Shuichi Ozawa Kazushi Yokomachi Toru Higaki Takehiro Shiinoki Yoshimi Ohno Yuji Murakami Kazuo Awai Yasushi Nagata 《Reports of Practical Oncology and Radiotherapy》2019,24(5):499-506
ObjectivesThe aim of the current study is to evaluate the accuracy and the precision of raw-data-based relative electron density (REDraw) and the calibration-based RED (REDcal) at a range of low-RED to high-RED for tissue-equivalent phantom materials by comparing them with reference RED (REDref) and to present the difference of REDraw and REDcal for the contrast medium using dual-energy CT (DECT).MethodsThe REDraw images were reconstructed by raw-data-based decomposition using DECT. For evaluation of the accuracy of the REDraw, REDref was calculated for the tissue-equivalent phantom materials based on their specified density and elemental composition. The REDcal images were calculated using three models: Lung-Bone model, Lung-Ti model and Lung-Ti (SEMAR) model which used single-energy metal artifact reduction (SEMAR). The difference between REDraw and REDcal was calculated.ResultsIn the titanium rod core, the deviations of REDraw and REDcal (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) from REDref were 0.45%, 50.8%, 15.4% and 15.0%, respectively. The largest differences between REDraw and REDcal (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) in the contrast medium phantom were 8.2%, ?23.7%, and 28.7%, respectively. However, the differences between REDraw and REDcal values were within 10% at 20 mg/ml. The standard deviation of the REDraw was significantly smaller than the REDcal with three models in the titanium and the materials that had low CT numbers.ConclusionThe REDcal values could be affected by beam hardening artifacts and the REDcal was less accurate than REDraw for high-Z materials as titanium.Advances in knowledgeThe raw-data-based reconstruction method could reduce the beam hardening artifact compared with image-based reconstruction and increase the accuracy for the RED estimation in high-Z materials, such as titanium and iodinated contrast medium. 相似文献
155.
Sugai Kyoko Mori Keigo Murakami Noriaki Kato Hidetoshi 《Journal of plant research》2019,132(6):759-775
Journal of Plant Research - Adaptive radiation is the diversification of a founding population into multiple taxa that are differentially adapted to diverse ecological niches. The three Callicarpa... 相似文献
156.
The specialization of herbivores among tree species is poorly understood despite its fundamental importance as a factor regulating
diversity. To examine the effect of tree species on larval community structure, the larval communities in 10 temperate deciduous
tree species that differed in leaf emergence pattern (flush- vs. intermediate-type) were seasonally surveyed. The newly developed
soft, nitrogen-rich leaves of all species became tough and nitrogen-poor as the season progressed. Following the changes in
leaf quality, two distinct seasonal lepidopteran larval communities emerged, with a marked turnover in early July. The beta
diversity, or dissimilarity, of species composition in the larval communities among tree species was higher in summer than
in spring. These results imply that the lepidopteran larval communities as a whole were supported by alpha diversity in spring
and by beta diversity in summer, demonstrating that the plant diversity of this forest could support a caterpillar community.
We examined the importance of spatio-temporal variations in leaf quality within and among tree species in promoting herbivore
diversity, although other factors, such as tree species phylogeny and predators, may also have a large effect on lepidopteran
larval communities. 相似文献
157.
Kubota F Murakami T Tajika Y Yorifuji H 《The International journal of developmental biology》2008,52(4):397-405
Here, we report the results of molecular cloning and expression analyses of a non-clustered protocadherin (pcdh), pcdh18 in zebrafish embryos. The predicted zebrafish pcdh18 protein shows 6566% identity and 7879% homology with its mammalian and Xenopus counterparts. It has a Disabled-1 binding motif in its cytoplasmic domain, which is characteristic of pcdh18. Zebrafish embryos expressed pcdh18 by the early gastrula stage, 6 h post-fertilization (hpf), in their animal cap but not in the germ ring or the shield. pcdh18 was expressed in the neural tube and the central nervous system (CNS) from 12 hpf. Some populations of cells in the lateral neural tube and spinal cord of 1218 hpf embryos expressed pcdh18, but expression in these cells disappeared by 24 hpf. The hindbrain of embryos at 2456 hpf expressed pcdh18 in cells closely adjacent to the rostral and caudal rhombomeric boundaries in a thread-like pattern running in the dorsoventral direction. The pcdh18-positive cells were localized in the ventral part of the hindbrain at 24 hpf and in the dorsal part from 36 hpf. pcdh18 was also expressed in the telencephalon, diencephalon, tectum, upper rhombic lip, retina and otic vesicle. Expression in the CNS decreased markedly before hatching. Pharyngeal arch primordia, arches, jaws and gills expressed pcdh18, and the molecule was also expressed in some endodermal cells in late embryos. 相似文献
158.
Junichi Nasu Kyoko Murakami Shoji Miyagawa Ryosuke Yamashita Tohru Ichimura Takaji Wakita Hak Hotta Tatsuo Miyamura Tetsuro Suzuki Tazuko Satoh Ikuo Shoji MD PhD 《Journal of cellular biochemistry》2010,111(3):676-685
E6‐associated protein (E6AP) is a cellular ubiquitin protein ligase that mediates ubiquitylation and degradation of tumor suppressor p53 in conjunction with the high‐risk human papillomavirus E6 protein. We previously reported that E6AP targets annexin A1 protein for ubiquitin‐dependent proteasomal degradation. To gain a better understanding of the physiological function of E6AP, we have been seeking to identify novel substrates of E6AP. Here, we identified peroxiredoxin 1 (Prx1) as a novel E6AP‐binding protein using a tandem affinity purification procedure coupled with mass spectrometry. Prx1 is a 25‐kDa member of the Prx family, a ubiquitous family of antioxidant peroxidases that regulate many cellular processes through intracellular oxidative signal transduction pathways. Immunoprecipitation analysis showed that E6AP binds Prx1 in vivo. Pull‐down experiments showed that E6AP binds Prx1 in vitro. Ectopic expression of E6AP enhanced the degradation of Prx1 in vivo. In vivo and in vitro ubiquitylation assays revealed that E6AP promoted polyubiquitylation of Prx1. RNAi‐mediated downregulation of endogenous E6AP increased the level of endogenous Prx1 protein. Taken together, our data suggest that E6AP mediates the ubiquitin‐dependent proteasomal degradation of Prx1. Our findings raise a possibility that E6AP may play a role in regulating Prx1‐dependent intracellular oxidative signal transduction pathways. J. Cell. Biochem. 111: 676–685, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
159.
Tetsuya Satoh Kosuke Tsuruta Yasuharu Shinoda Ryuichi Hirota Kenichi Noda Akio Kuroda Yuji Murakami 《Analytical biochemistry》2009,395(2):161-165
We constructed a novel ATP amplification reactor using a reciprocating-flow system to increase the number of ATP amplification cycles without an increase in backpressure. We previously reported a continuous-flow ATP amplification system that effectively and quantitatively amplified ATP and increased the sensitivity of a quantitative bioluminescence assay. However, it was difficult to increase the number of amplification cycles due to backpressure in the system. Because addition of immobilized adenylate kinase (ADK) and pyruvate kinase (PK) columns increased backpressure, the maximum number of ATP amplification cycles within column durability was only 4. In this study, ATP amplification was performed using a reciprocating-flow system, and 10 cycles of ATP amplification could be achieved without an increase in backpressure. As a result, ATP was amplified more than 100-fold after 10 cycles of reciprocating flow. The gradient of ATP amplification was approximately 1.76N. The backpressure on the columns was 0.03 MPa in 1–10 ATP amplification cycles, and no increases in backpressure were observed. 相似文献