A Novel EYA1 Mutation Causing Alternative RNA Splicing in a Chinese Family With Branchio-Oto Syndrome: Implications for Molecular Diagnosis and Clinical Application

Anhai Chen,Chufeng He,Yong Feng,Jie Ling,Xin Peng,Xianlin Liu,Shuang Mao,Yongjia Chen,Mengyao Qin,Shuai Zhang,Yijiang Bai,Jian Song,Zhili Feng,Lu Ma,Dinghua He,Lingyun Mei1 대한이비인후과학회 2023 Clinical and Experimental Otorhinolaryngology Vol.16 No.4

Objectives. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However,few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenicfactors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in thesepatients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the ge-netic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individualswithin the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis andclassified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing wasverified through a minigene assay. The predicted three-dimensional protein structure and biochemical experimentswere used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was fol-lowed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results. A novel heterozygous EYA1 splicing variant (c.1050+4 A >C) was identified and classified as pathogenic (PVS1(RNA),PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation mayimpair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellularmislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improvedhearing loss caused by bone-conduction abnormalities in the proband. Conclusion. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molec-ular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgeryprovides a reference for auditory rehabilitation in similar patients.

Introduction of Long-Term Care need Assessment Tool

Mei-Yin Liu,Shyh-Dye Lee 한국간호과학회 2011 한국간호과학회 학술대회 Vol.2011 No.10

PBK/TOPK Expression During TPA-Induced HL-60 Leukemic Cell Differentiation

Liu, Yu-Hong,Gao, Xue-Mei,Ge, Fan-Mei,Wang, Zhe,Wang, Wen-Qing,Li, Xiao-Yong Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: This study concerns expression of PBK/TOPK during differentiation of HL-60 leukemic cells induced by tetradecanoyl phorbol acetate (TPA). Methods: Wright-Giemsa staining was performed to observe morphological changes in the HL-60 cells, and flow cytometry was used to assess the cell cycle and CD11b, CD14, CD13, and CD33 expression. PBK/TOPK levels were determined by Western blot analysis. Results: After treating HL60 cells with $5.1{\times}10^{-9}$ mmol/L of TPA for three days, the number of nitroblue-tetrazolium-positive cells and CD11b, CD13, and CD14 expression increased, whereas the PBK/TOPK levels decreased. Conclusions: TPA can inhibit proliferation and induce differentiation of HL60 cells of the granulocytic or monocytic lineage. PBK/TOPK expression was downregulated during this process, whereas the Pho-PBK/TOPK expression was increased.

Expression of IER3 in Primary Hepatocarcinoma: Correlation with Clinicopathological Parameters

Liu, Zhong,Wang, Xin-Mei,Jia, Tong-Fu,Zhai, Yi,Sun, Ling-Yan,Cheng, Yu-Ping,Zhang, Yue-Min,Liu, Shi-Hai,Liang, Jun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: Studies indicate the immediate early response gene 3 (IER3) is involved in many biological processes. Recently, it was discovered that IER3 plays an important role in tumorigenesis and tumor progression. Thus it may be a valuable biomarker in tumor. This study was designed to investigate the expression status of IER3 in primary hepatocarcinoma (PHC) and correlation with clinicopathological parameters. Materials and Methods: Real-time PCR was performed to evaluate the expression levels of IER3 in 62 pathologically diagnosed human PHC specimens. Results: A statistically significant association was disclosed between the expression of IER3 and P53 mutant protein (short for P53), Ki-67, EGFR and the biggest diameter, differentiation grade of tumor. Conclusions: This work is the first to shed light on the potential clinical usefulness of IER3, as an efficient tumor biomarker in PHC.

Liquid/Liquid Interfacial Fabrication of Thermosensitive and Catalytically Active Ag Nanoparticle-Doped Block Copolymer Composite Foam Films

Liu, Mei,Wang, Qian,Geng, Yuanyuan,Wang, Changwei,Lee, Yong-Ill,Hao, Jingcheng,Liu, Hong-Guo American Chemical Society 2014 Langmuir Vol.30 No.34

<P>An aqueous solution of AgNO<SUB>3</SUB> (upper phase) and a DMF/CHCl<SUB>3</SUB> solution of polystyrene-<I>b</I>-poly(acryl acid)-<I>b</I>-polystyrene (PS-<I>b</I>-PAA-<I>b</I>-PS) or PS-<I>b</I>-PAA-<I>b</I>-PS/1,6-diaminohexane (DAH) (lower phase) constituted a planar liquid/liquid interface. The lower phase gradually transformed to a water-in-oil (W/O) emulsion via spontaneous emulsification due to the “ouzo effect”. Polymer molecules, DAH molecules, and Ag<SUP>+</SUP> ions assembled into microcapsules around emulsion droplets that adsorbed at the planar liquid/liquid interface, resulting in formation of a foam film. DAH acted as a cross-linker during this process. Transmission electron microscopic observations indicated that Ag nanoclusters that were generated through reduction of Ag<SUP>+</SUP> ions by DMF were homogeneously dispersed in the walls of the foam structure. X-ray photoelectron spectroscopic investigations revealed that Ag(I) and Ag(0) coexisted in the film, and Ag(I) transformed to Ag(0) after further treatment. The film formed without DAH was not stable, while the film formed with DAH was very stable due to intermolecular attraction between PAA and DAH and formation of amides, as revealed by FTIR spectra. The film formed with DAH exhibited high and durable catalytic activity for hydrogenation of nitro compounds and, very interestingly, exhibited thermoresponsive catalytic behavior.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/langd5/2014/langd5.2014.30.issue-34/la502738j/production/images/medium/la-2014-02738j_0012.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/la502738j'>ACS Electronic Supporting Info</A></P>

Trichloroethylene induces dopaminergic neurodegeneration in Fisher 344 rats

Liu, Mei,Choi, Dong-Young,Hunter, Randy L.,Pandya, Jignesh D.,Cass, Wayne A.,Sullivan, Patrick G.,Kim, Hyoung-Chun,Gash, Don M.,Bing, Guoying Blackwell Publishing Ltd 2010 Journal of Neurochemistry Vol.112 No.3

<P><I>J. Neurochem.</I> (2010) <B>112</B>, 773–783.</P><P>Abstract</P><P>Trichloroethylene, a chlorinated solvent widely used as a degreasing agent, is a common environmental contaminant. Emerging evidence suggests that chronic exposure to trichloroethylene may contribute to the development of Parkinson’s disease. The purpose of this study was to determine if selective loss of nigrostriatal dopaminergic neurons could be reproduced by systemic exposure of adult Fisher 344 rats to trichloroethylene. In our experiments, oral administration of trichloroethylene induced a significant loss of dopaminergic neurons in the substantia nigra pars compacta in a dose-dependent manner, whereas the number of both cholinergic and GABAergic neurons were not decreased in the striatum. There was a robust decline in striatal levels of 3, 4-dihydroxyphenylacetic acid without a significant depletion of striatal dopamine. Rats treated with trichloroethylene showed defects in rotarod behavior test. We also found a significantly reduced mitochondrial complex I activity with elevated oxidative stress markers and activated microglia in the nigral area. In addition, we observed intracellular &agr;-synuclein accumulation in the dorsal motor nucleus of the vagus nerve, with some in nigral neurons, but little in neurons of cerebral cortex. Overall, our animal model exhibits some important features of Parkinsonism, and further supports that trichloroethylene may be an environmental risk factors for Parkinson’s disease.</P>

Transformation of nitrogen-containing compounds in atmospheric residue by hydrotreating

Mei Liu,Lin-Zhou Zhang,Cheng Zhang,Sheng-Hua Yuan,De-Zhi Zhao,Lin-Hai Duan 한국화학공학회 2018 Korean Journal of Chemical Engineering Vol.35 No.2

Atmospheric residue from Saudi Arabia light crude oil was subjected to the hydrotreating process in a continuous fixed-bed reactor with hydrodesulfurization (HDS) and hydrodenitrogenation (HDN) catalysts. The detailed molecular composition of the polar heteroatom species in the feedstock and products was determined by electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) combined with other analytical methods. The ESI FT-ICR MS analysis indicates that the N1 class species have the highest relative abundance. In the hydrotreating process, small neutral N1 class species with high aromaticity and short side chains showed the highest relative abundance and were defined as easily removable compounds. High aromaticity and small molecule basic N1 compounds exhibited higher catalytic activity towards hydrogenation. The N1S1 class species were converted to the N1 class species, or even hydrocarbons, by the preferential removal of the sulfur atoms. Most of the N1O1 class species were difficult to remove, because of their stable chemical structure.

Ultra-sensitive graphene based mid-infrared plasmonic bio-chemical sensing using dielectric beads as a medium

Liu, Xiao,Zhang, Duan,Wu, Ye-Cun,Yang, Mei,Wang, Qian,Coileá,in, Cormac Ó,.,Xu, Hongjun,Yang, Chen,Abid, Mohamed,Abid, Mourad,Liu, Huajun,Chun, Byong Sun,Shi, Qingfan,Wu, Han-Chun Elsevier 2017 Carbon Vol.122 No.-

<P>Graphene is moving beyond the realm of simple electronic devices toward areas such as advanced biochemical sensing. The infrared (IR) response of graphene, characterized by collective long-lived charge-carrier oscillations, could be applied in IR-absorption spectroscopy, typically used for bio-chemical analysis. However, direct light absorption by propagating plasmons in graphene is forbidden due to the large momentum mismatch. Proposed methods to overcome this bottleneck come at a cost, the use of noble metal particles on graphene reduces the spectral bandwidth and nano-structuring graphene is expensive. Here, we propose a simple and cheap method to fabricate large scale ultra-sensitive graphene based mid-IR biosensors, by introducing dielectric beads to excite mid-IR range plasmons. Interference from waves scattered by the beads excite surface plasmon polaritons, which propagate several micrometers in graphene and enhance the interaction between the molecules and mid-IR light. This method opens an interesting window for the application of graphene in bio-chemical sensing. (C) 2017 Elsevier Ltd. All rights reserved.</P>

Mining Proteins Associated with Oral Squamous Cell Carcinoma in Complex Networks

Liu, Ying,Liu, Chuan-Xia,Wu, Zhong-Ting,Ge, Lin,Zhou, Hong-Mei Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

The purpose of this study was to construct a protein-protein interaction (PPI) network related to oral squamous cell carcinoma (OSCC). Each protein was ranked and those most associated with OSCC were mined within the network. First, OSCC-related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM) database. Then they were mapped to their protein identifiers and a seed set of proteins was built. The seed proteins were expanded using the nearest neighbor expansion method to construct a PPI network through the Online Predicated Human Interaction Database (OPHID). The network was verified to be statistically significant, the score of each protein was evaluated by algorithm, then the OSCC-related proteins were ranked. 38 OSCC related seed proteins were expanded to 750 protein pairs. A protein-protein interaction nerwork was then constructed and the 30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4, CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were mined using the nearest neighbor expansion method. The methods shown here may facilitate the discovery of important OSCC proteins and guide medical researchers in further pertinent studies.

The ROP mechanism study in hard formation drilling using local impact method

Liu, Weiji,Zhu, Xiaohua,Zhou, Yunlai,Mei, Liu,Meng, Xiannan,Jiang, Cheng Techno-Press 2018 Structural Engineering and Mechanics, An Int'l Jou Vol.68 No.1

The low rate of penetration and short lifetime of drilling bit served as the most common problems encountered in hard formation drilling, thus leading to severe restriction of drilling efficiency in oil and gas reservoir. This study developed a new local impact drilling method to enhance hard formation drilling efficiency. The limitation length formulas of radial/lateral cracks under static indentation and dynamic impact are derived based on the experimental research of Marshall D.B considering the mud column pressure and confining pressure. The local impact rock breaking simulation model is conducted to investigate its ROP raising effect. The results demonstrate that the length of radial/lateral cracks will increase as the decrease of mud pressure and confining pressure, and the local impact can result in a damage zone round the impact crater which helps the rock cutting, thus leading to the ROP increase. The numerical results also demonstrate the advantages of local impact method for raising ROP and the vibration reduction of bit in hard formation drilling. This study has shown that the local impact method can help raising the ROP and vibration reduction of bit, and it may be applied in drilling engineering.