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91.
Sato M Kikukawa T Araiso T Okita H Shimono K Kamo N Demura M Nitta K 《Biophysical chemistry》2003,104(1):209-216
Pharaonis halorhodopsin (phR) is an inward light-driven chloride ion pump from Natronobacterium pharaonis. In order to clarify the role of Ser-130(phR) residue which corresponds to Ser-115(shR) for salinarum hR on the anion-binding affinity, the wild-type and Ser-130 mutants substituted with Thr, Cys and Ala were expressed in E. coli cells and solubilized with 0.1% n-dodecyl beta-D-maltopyranoside The absorption maximum (lambda(max)) of the S130T mutant indicated a blue shift from that of the wild type in the absence and presence of chloride. For S130A, a large red shift (12 nm) in the absence of chloride was observed. The wild-type and all mutants showed the blue-shift of lambda(max) upon Cl(-) addition, from which the dissociation constants of Cl(-) were determined. The dissociation constants were 5, 89, 153 and 159 mM for the wild-type, S130A, S130T and S130C, respectively, at pH 7.0 and 25 degrees C. Circular dichroic spectra of the wild-type and the Ser-130 mutants exhibited an oligomerization. The present study revealed that the Ser-130 of N. pharaonis halorhodopsin is important for the chloride binding. 相似文献
92.
93.
Tomohiro Iguchi Sho Nambara Takaaki Masuda Hisateru Komatsu Masami Ueda Shinya Kidogami Yushi Ogawa Qingjiang Hu Kuniaki Sato Tomoko Saito Hidenari Hirata Shotaro Sakimura Ryutaro Uchi Naoki Hayashi Shuhei Ito Hidetoshi Eguchi Keishi Sugimachi Yoshihiko Maehara Koshi Mimori 《PloS one》2016,11(11)
miR-146a plays important roles in cancer as it directly targets NUMB, an inhibitor of Notch signaling. miR-146a is reportedly regulated by a G>C polymorphism (SNP; rs2910164). This polymorphism affects various cancers, including colorectal cancer (CRC). However, the clinical significance of miR-146a polymorphism in CRC remains unclear. A total of 59 patients with CRC were divided into 2 groups: a CC/CG genotype (n = 32) and a GG genotype (n = 27), based on the miR-146a polymorphism. cDNA microarray analysis was performed using 59 clinical samples. Significantly enriched gene sets in each genotype were extracted using GSEA. We also investigated the association between miR-146a polymorphism and miR-146a, NUMB expression or migratory response in CRC cell lines. The CC/CG genotype was associated with significantly more synchronous liver metastasis (p = 0.007). A heat map of the two genotypes showed that the expression profiles were clearly stratified. GSEA indicated that Notch signaling and JAK/STAT3 signaling were significantly associated with the CC/CG genotype (p = 0.004 and p = 0.023, respectively). CRC cell lines with the pre-miR-146a/C revealed significantly higher miR-146a expression (p = 0.034) and higher NUMB expression and chemotactic activity. In CRC, miR-146a polymorphism is involved in liver metastasis. Identification of this polymorphism could be useful to identify patients with a high risk of liver metastasis in CRC. 相似文献
94.
Shinichi Shimizu Naoki Miyamoto Taeko Matsuura Yusuke Fujii Masumi Umezawa Kikuo Umegaki Kazuo Hiramoto Hiroki Shirato 《PloS one》2014,9(4)
Purpose
A proton beam therapy (PBT) system has been designed which dedicates to spot-scanning and has a gating function employing the fluoroscopy-based real-time-imaging of internal fiducial markers near tumors. The dose distribution and treatment time of the newly designed real-time-image gated, spot-scanning proton beam therapy (RGPT) were compared with free-breathing spot-scanning proton beam therapy (FBPT) in a simulation.Materials and Methods
In-house simulation tools and treatment planning system VQA (Hitachi, Ltd., Japan) were used for estimating the dose distribution and treatment time. Simulations were performed for 48 motion parameters (including 8 respiratory patterns and 6 initial breathing timings) on CT data from two patients, A and B, with hepatocellular carcinoma and with clinical target volumes 14.6 cc and 63.1 cc. The respiratory patterns were derived from the actual trajectory of internal fiducial markers taken in X-ray real-time tumor-tracking radiotherapy (RTRT).Results
With FBPT, 9/48 motion parameters achieved the criteria of successful delivery for patient A and 0/48 for B. With RGPT 48/48 and 42/48 achieved the criteria. Compared with FBPT, the mean liver dose was smaller with RGPT with statistical significance (p<0.001); it decreased from 27% to 13% and 28% to 23% of the prescribed doses for patients A and B, respectively. The relative lengthening of treatment time to administer 3 Gy (RBE) was estimated to be 1.22 (RGPT/FBPT: 138 s/113 s) and 1.72 (207 s/120 s) for patients A and B, respectively.Conclusions
This simulation study demonstrated that the RGPT was able to improve the dose distribution markedly for moving tumors without very large treatment time extension. The proton beam therapy system dedicated to spot-scanning with a gating function for real-time imaging increases accuracy with moving tumors and reduces the physical size, and subsequently the cost of the equipment as well as of the building housing the equipment. 相似文献95.
Akira Inoue Naoki Yamamoto Masatsugu Kimura Koji Nishio Hideo Yamane Koichi Nakajima 《FEBS letters》2014
RBM10, originally called S1-1, is a nuclear RNA-binding protein with domains characteristic of RNA processing proteins. It has been reported that RBM10 constitutes spliceosome complexes and that RBM5, a close homologue of RBM10, regulates alternative splicing of apoptosis-related genes, Fas and cFLIP. In this study, we examined whether RBM10 has a regulatory function in splicing similar to RBM5, and determined that it indeed regulates alternative splicing of Fas and Bcl-x genes. RBM10 promotes exon skipping of Fas pre-mRNA as well as selection of an internal 5′-splice site in Bcl-x pre-mRNA. We propose a consensus RBM10-binding sequence at 5′-splice sites of target exons and a mechanistic model of RBM10 action in the alternative splicing. 相似文献
96.
Youichi Suzuki Wei-Xin Chin Qi'En Han Koji Ichiyama Ching Hua Lee Zhi Wen Eyo Hirotaka Ebina Hirotaka Takahashi Chikako Takahashi Beng Hui Tan Takayuki Hishiki Kenji Ohba Toshifumi Matsuyama Yoshio Koyanagi Yee-Joo Tan Tatsuya Sawasaki Justin Jang Hann Chu Subhash G. Vasudevan Kouichi Sano Naoki Yamamoto 《PLoS pathogens》2016,12(1)
Dengue virus (DENV) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN) response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN). Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), and La motif-related protein 1 (LARP1). Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells. 相似文献
97.
Akira Ishio Takeshi Sasamura Tomonori Ayukawa Junpei Kuroda Hiroyuki O. Ishikawa Naoki Aoyama Kenjiroo Matsumoto Takuma Gushiken Tetsuya Okajima Tomoko Yamakawa Kenji Matsuno 《The Journal of biological chemistry》2015,290(1):505-519
Notch (N) is a transmembrane receptor that mediates the cell-cell interactions necessary for many cell fate decisions. N has many epidermal growth factor-like repeats that are O-fucosylated by the protein O-fucosyltransferase 1 (O-Fut1), and the O-fut1 gene is essential for N signaling. However, the role of the monosaccharide O-fucose on N is unclear, because O-Fut1 also appears to have O-fucosyltransferase activity-independent functions, including as an N-specific chaperon. Such an enzymatic activity-independent function could account for the essential role of O-fut1 in N signaling. To evaluate the role of the monosaccharide O-fucose modification in N signaling, here we generated a knock-in mutant of O-fut1 (O-fut1R245A knock-in), which expresses a mutant protein that lacks O-fucosyltransferase activity but maintains the N-specific chaperon activity. Using O-fut1R245A knock-in and other gene mutations that abolish the O-fucosylation of N, we found that the monosaccharide O-fucose modification of N has a temperature-sensitive function that is essential for N signaling. The O-fucose monosaccharide and O-glucose glycan modification, catalyzed by Rumi, function redundantly in the activation of N signaling. We also showed that the redundant function of these two modifications is responsible for the presence of N at the cell surface. Our findings elucidate how different forms of glycosylation on a protein can influence the protein''s functions. 相似文献
98.
Hiroki Tsumoto Syo Kawahara Yuki Fujisawa Takayoshi Suzuki Hidehiko Nakagawa Kohfuku Kohda Naoki Miyata 《Bioorganic & medicinal chemistry letters》2010,20(6):1948-1952
Water-soluble [60]fullerene (C60) derivatives were synthesized to examine their bioactivities. PC12 cells were used as a model of nerve cells and the bioactivities of synthesized C60 derivatives together with some reported ones were tested. Among the compounds tested, C60/(γ-CyD)2, C60-bis(γ-CyD) (5) containing C60-mono(γ-CyD) (5′), and C60/PVP were sufficiently soluble in water and showed an enhancing effect on the neurite outgrowth of NGF-treated PC12 cells. 相似文献
99.
Resistance to Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis and constitutive expression of Apo2L/TRAIL in human T-cell leukemia virus type 1-infected T-cell lines 下载免费PDF全文
Matsuda T Almasan A Tomita M Uchihara JN Masuda M Ohshiro K Takasu N Yagita H Ohta T Mori N 《Journal of virology》2005,79(3):1367-1378
Adult T-cell leukemia (ATL), a CD4+-T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1), is difficult to cure, and novel treatments are urgently needed. Apo2 ligand (Apo2L; also tumor necrosis factor-related apoptosis-inducing ligand [TRAIL]) has been implicated in antitumor therapy. We found that HTLV-1-infected T-cell lines and primary ATL cells were more resistant to Apo2L-induced apoptosis than uninfected cells. Interestingly, HTLV-1-infected T-cell lines and primary ATL cells constitutively expressed Apo2L mRNA. Inducible expression of the viral oncoprotein Tax in a T-cell line up-regulated Apo2L mRNA. Analysis of the Apo2L promoter revealed that this gene is activated by Tax via the activation of NF-kappaB. The sensitivity to Apo2L was not correlated with expression levels of Apo2L receptors, intracellular regulators of apoptosis (FLICE-inhibitory protein and active Akt). NF-kappaB plays a crucial role in the pathogenesis and survival of ATL cells. The resistance to Apo2L-induced apoptosis was reversed by N-acetyl-L-leucinyl-L-leucinyl-lLnorleucinal (LLnL), an NF-kappaB inhibitor. LLnL significantly induced the Apo2L receptors DR4 and DR5. Our results suggest that the constitutive activation of NF-kappaB is essential for Apo2L gene induction and protection against Apo2L-induced apoptosis and that suppression of NF-kappaB may be a useful adjunct in clinical use of Apo2L against ATL. 相似文献
100.
Amplified genes in cancer cells reside on extrachromosomal double minutes (DMs) or chromosomal homogeneously staining regions (HSRs). We used a plasmid bearing a mammalian replication initiation region to model gene amplification. Recombination junctions in the amplified region were comprehensively identified and sequenced. The junctions consisted of truncated direct repeats (type 1) or inverted repeats (type 2) with or without spacing. All of these junctions were frequently detected in HSRs, whereas there were few type 1 or a unique type 2 flanked by a short inverted repeat in DMs. The junction sequences suggested a model in which the inverted repeats were generated by sister chromatid fusion. We were consistently able to detect anaphase chromatin bridges connected by the plasmid repeat, which were severed in the middle during mitosis. De novo HSR generation was observed in live cells, and each HSR was lengthened more rapidly than expected from the classical breakage/fusion/bridge model. Importantly, we found massive DNA synthesis at the broken anaphase bridge during the G1 to S phase, which could explain the rapid lengthening of the HSR. This mechanism may not operate in acentric DMs, where most of the junctions are eliminated and only those junctions produced through stable intermediates remain. 相似文献