著者
Lei Wang Zhuo Shao Shiyue Chen Lu Shi Zhaoshen Li
出版者
東北ジャーナル刊行会
雑誌
The Tohoku Journal of Experimental Medicine (ISSN:00408727)
巻号頁・発行日
vol.241, no.4, pp.287-295, 2017 (Released:2017-04-11)
参考文献数
38
被引用文献数
7

Pancreatic ductal adenocarcinoma (PDAC) presents as an aggressive malignancy caused by environmental and genetic factors. In order to identify causal genes for PDAC, we performed whole exome sequencing (WES) to detect gene mutations in seven pairs of PDAC tissue and adjacent non-tumor tissue samples. Finally, we found a new nonsynonymous single nucleotide variant (nsSNV) in solute carrier 24 family member 2 (SLC24A2) gene resulting in the substitution of native glutamic acid (E) into aspartic acid (D) at position of 287 amino acid (E287D) in SLC24A2 protein, and confirmed this variant by Sanger gene sequencing. SLC24A2 is a potassium-dependent sodium-calcium exchanger and can transport metal ion across cell membrane. Multiple in silico variants’ effects analyses methods including SIFT, PolyPhen, PROVEAN, and PANTHER demonstrated this variant had probably damaging effects, which was consistent with the results obtained from Mutation Taster software analysis with a probability of 0.99999997 to be “disease causing.” The three dimension (3D) structure analysis results suggested this variant had little effects on the solubility and hydrophobicity of the protein; but it could decrease the protein stability by increasing the total protein structure energy (−8874.33 kJ/mol for the mutant and −8963.54 kJ/mol for the native) and by causing the mutant protein decreasing three stabilizing residues. Less stability of the mutant 287D protein than the native E287 protein was also supported by I-Mutant and Western-blotting analysis results. Overall, a new mutation in SLC24A2 gene was identified to decrease the stability of SLC24A2, which may have potential clinical usages.
著者
Can-Zhao Liu Xiang-Yu Li Ren-Hong Du Min Gao Ming-Ming Ma Fei-Ya Li Er-Wen Huang Hong-Shuo Sun Guan-Lei Wang Yong-Yuan Guan
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-16-0793, (Released:2016-10-19)
参考文献数
41
被引用文献数
13

Background:Previous research has demonstrated that ClC-3 is responsible for volume-regulated Cl–current (ICl.vol) in vascular smooth muscle cells (VSMCs). However, it is still not clear whether and how ClC-3 is transported to cell membranes, resulting in alteration ofICl.vol.Methods and Results:Volume-regulated chloride current (ICl.vol) was recorded by whole-cell patch clamp recording, and Western blotting and co-immunoprecipitation were performed to examine protein expression and protein-protein interaction. Live cell imaging was used to observe ClC-3 transporting. The results showed that an overexpression of endophilin A2 could increaseICl.vol, while endophilin A2 knockdown decreasedICl.vol. In addition, the SH3 domain of endophilin A2 mediated its interaction with ClC-3 and promotes ClC-3 transportation from the cytoplasm to cell membranes. The regulation of ClC-3 channel activity was also verified in basilar arterial smooth muscle cells (BASMCs) isolated from endophilin A2 transgenic mice. Moreover, endophilin A2 increase VSMCs proliferation induced by endothelin-1 or hypo-osmolarity.Conclusions:The present study identified endophilin A2 as a ClC-3 channel partner, which serves as a new ClC-3 trafficking insight in regulatingICl.volin VSMCs. This study provides a new mechanism by which endophilin A2 regulates ClC-3 channel activity, and sheds light on how ClC-3 is transported to cell membranes to play its critical role as a chloride channel in VSMCs function, which may be involved in cardiovascular diseases.
著者
Akihiro Ito Lei Wang Ryotaro Notomi Shigeki Sasaki Yosuke Taniguchi
出版者
The Pharmaceutical Society of Japan
雑誌
Chemical and Pharmaceutical Bulletin (ISSN:00092363)
巻号頁・発行日
vol.72, no.1, pp.16-20, 2024-01-01 (Released:2024-01-01)
参考文献数
24

Triplex DNA formation has generated much interest as a genomic targeting tool that directly targets duplex DNA. However, fundamental limitations in the base pairs of target duplex DNA sequences that can form stable triplex DNA have limited the application. Recently, we have reported on the recognition of CG and 5mCG base pairs by artificial nucleic acid derivatives with a 2′-deoxynebularine skeleton. Therefore, we attempted to explore the basic skeleton that is important for the development of new artificial nucleic acids allowing for the recognition of TA base pairs. In this study, we focused on a benzimidazole skeleton and introduced a hydroxyl group to enable one-point hydrogen bonding. We have synthesized artificial nucleoside analogues with hydroxyl group on the benzimidazole and incorporated their amidite derivatives into triplex forming oligonucleotides (TFOs). The gel shift assay was performed to evaluate the triplex DNA formation ability of synthesized TFOs, and TFOs containing hydroxybenzimidazole were successfully recognized TA base pairs for all four different sequences. Moreover, compared to the results for the TFOs containing benzimidazole, which suggested hydrogen bonding formation at the hydroxyl group. Therefore, hydroxybenzimidazole would be an important artificial nucleic acid skeleton for TA base pair recognition.
著者
Hangjin SUN Lei WANG Zhaoyang QIU Qi ZHANG
出版者
The Institute of Electronics, Information and Communication Engineers
雑誌
IEICE TRANSACTIONS on Fundamentals of Electronics, Communications and Computer Sciences (ISSN:09168508)
巻号頁・発行日
vol.E105-A, no.12, pp.1616-1620, 2022-12-01

The Nyquist folding receiver (NYFR) is a novel analog-to-information architecture, which can achieve wideband receiving with a small amount of system resource. The NYFR uses a radio frequency (RF) non-uniform sampling to realize wideband receiving, and the practical RF non-uniform sample pulse train usually contains an aperture. Therefore, it is necessary to investigate the aperture impact on the NYFR output. In this letter, based on the NYFR output signal to noise ratio (SNR), the aperture impact on the NYFR is analyzed. Focusing on the aperture impact, the corresponding NYFR output signal power and noise power are given firstly. Then, the relation between the aperture and the output SNR is analyzed. In addition, the output SNR distribution containing the aperture is investigated. Finally, combing with a parameter estimation method, several simulations are conducted to prove the theoretical aperture impact.
著者
Chenze SHI Lei WANG Kejun ZHOU Mingmei SHAO Yifei LU Tao WU
出版者
Center for Academic Publications Japan
雑誌
Journal of Nutritional Science and Vitaminology (ISSN:03014800)
巻号頁・発行日
vol.66, no.6, pp.536-544, 2020-12-31 (Released:2020-12-31)
参考文献数
30
被引用文献数
8

To investigate changes in serum and hepatic levels of amino acids in ALD and to provide novel evidence and approaches for the prevention and treatment of ALD. Twenty specific pathogen-free SD male rats were devided into two groups, ten for the control group, and ten for the model group. Serum biochemical markers, including alanine aminotransferase, aspartate aminotransferase, laminin and hyaluronidase were measured. Histological analysis of liver tissues was performed. Serum and liver amino acids levels were quantitatively determined by ultra-high-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-TQMS)-based targeted metabolomics. Compared with the normal group, ALD rats showed an obvious increase in the levels of β-alanine, alanine, serine, ornithine, tyrosine and the tyrosine ratio, while there was a decrease in arginine levels, the BTR ratio and Fischer’s ratio in serum. Additionally, ALD rats exhibited a significant increase in the levels of cysteine and putrescine, while there was a decrease in sarcosine, β-alanine, serine, proline, valine, threonine, ornithine, lysine, histidine, tyrosine, symmetric dimethylarginine, methionine, isoleucine and methionine-sulfoxide levels in liver tissues compared with the normal group. The serum and liver amino acids showed significant changes in ALD rats and can be considered as potential specific diagnostic biomarkers for ALD.