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.

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.

A Novel Stabilizing Control for Neural Nonlinear Systems with Time Delays by State and Dynamic Output Feedback

Mei-Qin Liu,Hui-Fang Wang 대한전기학회 2008 International Journal of Control, Automation, and Vol.6 No.1

A novel neural network model, termed the standard neural network model (SNNM), similar to the nominal model in linear robust control theory, is suggested to facilitate the synthesis of controllers for delayed (or non-delayed) nonlinear systems composed of neural networks. The model is composed of a linear dynamic system and a bounded static delayed (or non-delayed) nonlinear operator. Based on the global asymptotic stability analysis of SNNMs, Static state-feedback controller and dynamic output feedback controller are designed for the SNNMs to stabilize the closed-loop systems, respectively. The control design equations are shown to be a set of linear matrix inequalities (LMIs) which can be easily solved by various convex optimization algorithms to determine the control signals. Most neural-network-based nonlinear systems with time delays or without time delays can be transformed into the SNNMs for controller synthesis in a unified way. Two application examples are given where the SNNMs are employed to synthesize the feedback stabilizing controllers for an SISO nonlinear system modeled by the neural network, and for a chaotic neural network, respectively. Through these examples, it is demonstrated that the SNNM not only makes controller synthesis of neural-network-based systems much easier, but also provides a new approach to the synthesis of the controllers for the other type of nonlinear systems.

A Novel Approach Based on Fluid Dynamics for On-Site Safety Assessment

Mei Liu,Heap-Yih Chong,Pin-Chao Liao 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.5

Construction safety assessment is a major component of safety management in construction projects. However, thus far, most assessment studies have focused on either cross-sectional or longitudinal performance. This study aims to develop a proactive and preliminary safety assessment method using a fluid dynamics (FD) approach by integrating longitudinal contractor performance with cross-sectional safety conditions. To this end, an FD framework was first developed using three processes: (a) identifying the connections between FD principles and safety analogs, (b) incorporating the Darcy–Weisbach equation into the framework, and (c) modifying FD equations for construction safety assessment. Subsequently, two case studies were investigated, and the results obtained were compared and verified with one existing assessment results. The results indicate that the state of safety at a construction site incorporates both the occurrence of hazards and conservation of energy. Thus, the proposed FD approach can be used to preliminarily assess and predict safety conditions by combining safety-related measures with the dynamic characteristics of construction processes. The approach considers a comprehensive range of indicators and parameters, which enables the comparison of safety performance between projects or assessment periods by independently changing parameters.

H∞ Synchronization of Two Different Discrete-Time Chaotic Systems via a Unified Model

Mei-Qin Liu,Haiyang Chen,Senlin Zhang,Weihua Sheng 제어·로봇·시스템학회 2015 International Journal of Control, Automation, and Vol.13 No.1

This paper presents some novel synchronization methods for two discrete-time chaotic systems with different time delays, which are transformed into two unified models. First, the H∞ performance of the synchronization error dynamical system between the drive unified model and the response one is analyzed using the linear matrix inequality (LMI) approach. Second, the novel state feedback controllers are established to guarantee H∞ performance for the overall system. The parameters of these controllers are determined by solving the eigenvalue problem (EVP). Most discrete-time chaotic systems with or without time delays can be converted into this unified model, and H∞ synchronization controllers are designed in a unified way. The effectiveness of the proposed design methods are demonstrated by three numerical examples.

Multi-Sensor Multi-Target Passive Locating and Tracking

Mei Liu,Nuo Xu,Haihao Li 대한전기학회 2007 International Journal of Control, Automation, and Vol.5 No.2

The passive direction finding cross localization method is widely adopted in passive tracking, therefore there will exist masses of false intersection points. Eliminating these false intersection points correctly and quickly is a key technique in passive localization. A new method is proposed for passive locating and tracking multi-jammer target in this paper. It not only solves the difficulty of determining the number of targets when masses of false intersection points existing, but also solves the initialization problem of elastic network. Thus this method solves the problem of multi-jammer target correlation and the elimination of static false intersection points. The method which dynamically establishes multiple hypothesis trajectory trees solves the problem of eliminating the remaining false intersection points. Simulation results show that computational burden of the method is lower, the elastic network can more quickly find all or most of the targets and have a more probability of locking the real targets. This method can eliminate more false intersection points.

Using tyrosinase as a tri-modality reporter gene to monitor transplanted stem cells in acute myocardial infarction

Mei Liu,Yichun Wang,Mengting Li,Hongyan Feng,Qingyao Liu,Chunxia Qin,Yongxue Zhang,Xiaoli Lan 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

The study aimed to investigate the feasibility of noninvasive monitoring of bone marrow mesenchymal stem cells (MSCs) transduced with the tyrosinase reporter gene for acute myocardial infarction (AMI) with photoacoustic imaging (PAI), magnetic resonance imaging (MRI), and positron emission tomography (PET) in vitro and in vivo. MSCs were transduced with a lentivirus carrying a tyrosinase reporter gene. After transduction, the rate of 18F-5-fluoro-N-(2- [diethylamino]ethyl)picolinamide (18F-5-FPN) uptake was measured. PAI and MRI of stable cell lines expressing tyrosinase (TYR-MSCs) were performed in vitro. An AMI model was induced and verified. TYR-MSCs and MSCs were injected into the margins of the infarcted areas, and PAI, MRI, and PET images were acquired 1, 7, 14, 21, and 28 days after cell injection. Sham-operated models without injection were used as the control group. TYR-MSCs showed noticeably higher uptake of 18F-5-FPN and stronger signals in T1-weighted MRI and PAI than non-transduced MSCs. In vivo studies revealed prominent signals in the injected area of the infarcted myocardium on PAI/MRI/PET images, whereas no signal could be seen in rats injected with non-transduced MSCs or sham-operated rats. The uptake values of 18F-5-FPN in vivo showed a slight decrease over 28 days, whereas MRI and PAI signal intensity decreased dramatically. MSCs stably transduced with the tyrosinase reporter gene could be monitored in vivo in myocardial infarction models by PET, MRI, and PAI, providing a feasible and reliable method for checking the viability, location, and dwell time of transplanted stem cells.

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.

Antenatal Depression in East Asia: A Review of the Literature

Mei-Chun Hsiao,Mei-Chun Hsiao,Chia-Yih Liu 대한신경정신의학회 2012 PSYCHIATRY INVESTIGATION Vol.9 No.2

This current study’s goal is to summarize the literature regarding Antenatal Depression (AD) in the East Asian countries of Taiwan, China (including Hong Kong and Macau), Japan, and Korea. The main search utilized a Pub med Chinese Electronic Periodical Service (CEPS) literature review using keywords ‘AD’, and ‘Prenatal Depression’ with searches for ‘Japan’, ‘Korea’, ‘Taiwan’, ‘Hong Kong’ and Macau’. The rates of AD in East Asia appear to be relatively close to those in the Western literature, although certain studies showed slightly decreased rates. Many of the risk factors for AD were the same in the Eastern and Western literature. These risk factors included demographic factors such as younger age, smoking, low education and income, and unemployment. Other risk factors were physical symptoms such as menstrual pains and nausea. Finally, psychological factors such as a poor response to the pregnancy, poor spousal support, and poor family support were associated with AD. With regard to treatment, there were no studies examining the administration of psychotropic medications for AD. The literature from East Asia both confirmed many Western findings and made unique contributions to the literature on AD. The treatment of AD in East Asia appears to be an entity which, despite its morbidity, has not been adequately studied.

Bioconversion of ginsenoside Rc into Rd by a novel α-L-arabinofuranosidase, Abf22-3 from Leuconostoc sp. 22-3: cloning, expression, and enzyme characterization.

Liu, Qing-Mei,Jung, Hae-Min,Cui, Chang-Hao,Sung, Bong-Hyun,Kim, Jin-Kwang,Kim, Song-Gun,Lee, Sung-Taik,Kim, Sun-Chang,Im, Wan-Taek N.V. Swets en Zeitlinger 2013 Antonie van Leeuwenhoek Vol.103 No.4

<P>A novel α-L-arabinofuranosidase (Abf22-3) that could biotransform ginsenoside Rc into Rd was obtained from the ginsenoside converting Leuconostoc sp. strain 22-3, isolated from the Korean fermented food kimchi. The gene, termed abf22-3, consisting of 1,527 bp and encoding a protein with a predicted molecular mass of 58,486 Da was cloned into the pMAL-c2x (TEV) vector. A BLAST search using the Abf22-3's amino acid sequence revealed significant homology to that of family 51 glycoside hydrolases. The over-expressed recombinant Abf22-3 in Escherichia coli BL21 (DE3) catalyzed the hydrolysis of the arabinofuranoside moiety attached to the C-20 position of ginsenoside Rc under optimal conditions of pH 6.0 and 30 C. This result indicated that Abf22-3 selectively converts ginsenoside Rc into Rd, but did not catalyze the hydrolysis of glucopyranosyl groups from Rc or other ginsenosides such as Rb1 and Rb2. Over-expressed recombinant enzymes were purified by two steps with amylose-affinity and DEAE-cellulose chromatography and then characterized. The kinetic parameters for α-L-arabinofuranosidase showed apparent Km and Vmax values of 0.95 0.02 μM and 1.2 0.1 μmol min(-1) mg of protein(-1) against p-nitrophenyl-α-L-arabinofuranoside, respectively. Using a purified MBP-Abf22-3 (10 μg/ml), 0.1 % of ginsenoside Rc was completely converted to ginsenoside Rd within 20 min.</P>