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.

이광수의 '무정'과 장한수의 '제소인연' 비교연구

장춘매(Zhang, Chun-Mei) 한국문학회 2010 韓國文學論叢 Vol.56 No.-

20세기 초에 유가사상에 젖어 있었던 중한 양국은 서구문화의 영향으로 근대화로 진입하기 시작했다. 중한 양국 근대과도기의 연애와 혼인에 관한 인식을 밝히기 위해 본고는 한국 작가 이광수의 <무정>과 중국 작가 장한수의 <제소인연>을 비교했다. 두 작품은 모두 당대 사람들에게 익숙하지 않은 자유연애 이야기를 서술하고 있다. 본고는 이 두 작품을 주제, 인물, 서사법 등 여러 측면에서 비교하여 그 공통점과 차이점을 찾아낼 뿐만 아니라 작가 이광수와 장한수가 자유연애에 대해 주장하는 관점도 규명했다. 그리고 주제와 문체의 차원에서 두 작품이 전통문학을 계승하면서 개혁해 나아가는 측면도 고찰하였다. As the twentieth century began, both Korea and China featured with the traditional Confucianism started towards modern societies thanks to the influence of western culture. To expound the general viewpoints of the two countries on marriage at the transitional time, the paper is intended to make a comparative study of two works--Mu Jeong by Korean writer Lee Kwang-soo and Ti xiao yin yuan by Chinese writer Zhang Hen-shui. The two works both tell stories about people’s freedom to choose their spouses--a new concept unfamiliar to peoples at that time in both countries. The paper is designed to seek out the differences and similarities between the two novels from the aspects of themes, characterizations, and narrative methods and is an attempt to make a study of the propositions of both Lee Kwang-soo and Zhang Hen-shui on the freedom to choose one's spouse. Besides, the paper is also an effort to study what the two writers inherit from their respective traditional literatures and what is invented by the two.

Soy Protein Supplementation Reduces Clinical Indices in Type 2 Diabetes and Metabolic Syndrome

Xi-Mei Zhang,Yun-Bo Zhang,Mei-Hua Chi 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.3

Purpose: Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). Materials and Methods: We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. Results: The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessmentfor insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, -0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, -0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (≥6 mo) significantly reducedFPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. Conclusion: Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma.

Tax is Involved in Up-regulation of HMGB1 Expression Levels by Interaction with C/EBP

Zhang, Chen-Guang,Wang, Hui,Niu, Zhi-Guo,Zhang, Jing-Jing,Yin, Ming-Mei,Gao, Zhi-Tao,Hu, Li-Hua Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

The high mobility group box 1 (HMGB1) protein is a multifunctional cytokine-like molecule that plays an important role in the pathogenesis of tumors. In this study, real-time polymerase chain reactions and Western blot assays indicated that HMGB1 transcriptional activity and protein level are increased in $Tax^+$-T cells (TaxP). To clarify the mechanisms, a series of HMGB1 deletion reporter plasmids (pHLuc1 to pHLuc6) were transfected into $Tax^-$-T cells (TaxN, Jurkat) and $Tax^+$-T cells (TaxP). We found that promoter activity in $Tax^+$-T cells to be higher than that in $Tax^-$-T cells, indicating a significant increase in pHLuc6. Bay11-7082 (NF-${\kappa}B$ inhibitor) treatment did not block the enhancing effect. Chromatin immunoprecipitation assays revealed that Tax was retained on a HMGB1 promoter fragment encompassing -1163 to -975. Bioinformatics analysis showed six characteristic cis-elements for CdxA, AP-1, AML-1a, USF, v-Myb, and C/EBP in the fragment in question. Mutation of cis-elements for C/EBP reduced significant HMGB1 promoter activity induced by Tax. These findings indicate that Tax enhances the expression of HMGB1 gene at the transcriptional level, possibly by interacting with C/EBP.

Genotoxicity of Zizyphi Spinosi Semen in Bacterial Reverse Mutation (Ames) Test, Chromosomal Aberration and Micronucleus Test in Mice

Mei-Shu Zhang,박철범,방인석,강창수 한국식품위생안전성학회 2012 한국식품위생안전성학회지 Vol.27 No.2

Zizyphi spinosi semen (Z. spinosi) has been used in traditional Chinese medicine for the treatment of rheumatoid arthritis and wounds. However, toxicity in high doses was often observed due to the presence of alkaloids. This study was conducted to investigate the potential genotoxicity of Z. spinosi in vitro and in vivo. This was examined by the Bacterial reverse mutation (Ames) test using Salmonella typhimurium TA98, TA100, TA1535,TA1537 and Escherichia coli WP2uvrA, Chromosomal aberration was investigated using Chinese hamster lung cells and the micronucleus test using mice. Z. Spinosi did not induce mutagenicity in the Ames test, and it did not produce chromosomal aberration in Chinese hamster lung cells with and without metabolic activation, nor in the micronucleated polychromatic erythrocytes in the bone marrow cells in mice. Based on these results, it is concluded that Z. spinosi does not have mutagenic potential under the conditions examined in each study.

MAGED4 Expression in Glioma and Upregulation in Glioma Cell Lines with 5-Aza-2'-Deoxycytidine Treatment

Zhang, Qing-Mei,Shen, Ning,Xie, Sha,Bi, Shui-Qing,Luo, Bin,Lin, Yong-Da,Fu, Jun,Zhou, Su-Fang,Luo, Guo-Rong,Xie, Xiao-Xun,Xiao, Shao-Wen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.

Characterization of Marinilongibacter aquaticus gen. nov., sp. nov., a unique marine bacterium harboring four CRISPR-Cas systems in the phylum Bacteroidota

Zhang Dao-Feng,Yao Yu-Fang,Xue Hua-Peng,Fu Zi-Yue,Zhang Xiao-Mei,Shao Zongze 한국미생물학회 2022 The journal of microbiology Vol.60 No.9

A novel bacterium, designated YYF0007T, was isolated from an agar-degrading co-culture. The strain was found harboring four CRISPR-Cas systems of two classes in the chromosome and subsequently subjected to a study on polyphasic taxonomy. Pairwise analyses of the 16S rRNA gene sequences indicated that strain YYF0007T had highest 16S rRNA gene sequence similarity (92.2%) to Jiulongibacter sediminis JN- 14-9T. The phylogenomic trees based on the 16S rRNA gene and 269 single-copy orthologous gene clusters (OCs) indicated that strain YYF0007T should be recognized as a novel genus of the family Spirosomaceae. The cells were Gramstain- negative, nonmotile, strictly aerobic, and straight long rods with no flagellum. Optimum growth occurred at 28°C and pH 7.0 with the presence of NaCl concentration 1.0–3.0% (w/v). The strain showed oxidase and catalase activities. The major fatty acids were C16:1ω5c, iso-C15:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The predominant isoprenoid quinone was MK-7. The complete genome size was 4.64 Mb with a DNA G + C content of 44.4%. Further typing of CRISPR-Cas systems in the family Spirosomaceae and the phylum Bacteroidota indicated that it was remarkable for strain YYF0007T featured by such a set of CRISPR-Cas systems. This trait highlights the applications of strain YYF- 0007T in studies on the evolutionary dynamics and bacterial autoimmunity of CRISPR-Cas system as a potential model. The name Marinilongibacter aquaticus gen. nov., sp. nov. is proposed, and the type strain is YYF0007T (= MCCC 1K06017T = GDMCC 1.2428T = JCM 34683T).

Segmentation for Range Image Based on Snake Active Contour Model

Zhang Mei,Wen Jing Hua,Peng Xing Xing 보안공학연구지원센터 2016 International Journal of Signal Processing, Image Vol.9 No.8

Range image segmentation is one of the most common problem in the field of computer vision. In view of the defect about traditional range image segmentation methods, this paper introduces a new range image segmentation method based on snake active contour model (SCAM). First, this paper expresses the snake active contour model in the form of parameters, and illustrates the contour line data points inside and outside of the movement and pseudo code description of the motion of a point algorithm; then constructs energy function, pushing the Euler equation and discretization; finally gets the results by Cholesky decomposition. Numerical experiment results show that the method is accurate and efficient, of good effect and the segmentation results are consistent with human subjective visual perception.

Surface modified cellulose nanocrystals for tailoring interfacial miscibility and microphase separation of polymer nanocomposites

Zhang, Jinlong,Li, Mei-Chun,Zhang, Xiuqiang,Ren, Suxia,Dong, Lili,Lee, Sunyoung,Cheng, H. N.,Lei, Tingzhou,Wu, Qinglin Springer-Verlag 2019 CELLULOSE Vol.26 No.7

Differences in the biological properties of mesenchymal stromal cells from traumatic temporomandibular joint fibrous and bony ankylosis: a comparative study

Zhang Pei-Pei,Liang Su-Xia,Wang Hua-Lun,Yang Kun,Nie Shao-Chen,Zhang Tong-Mei,Tian Yuan-Yuan,Xu Zhao-Yuan,Chen Wei,Yan Ying-Bin 한국통합생물학회 2021 Animal cells and systems Vol.25 No.5

The aim of this study was to compare the functional characteristics of mesenchymal stromal cells (MSCs) from a sheep model of traumatic temporomandibular joint (TMJ) fibrous and bony ankylosis. A sheep model of bilateral TMJ trauma-induced fibrous ankylosis on one side and bony ankylosis on the contralateral side was used. MSCs from fibrous ankylosed callus (FAMSCs) or bony ankylosed callus (BA-MSCs) at weeks 1, 2, 4, and 8 after surgery were isolated and cultured. MSCs derived from the bone marrow of the mandibular condyle (BM-MSCs) were used as controls. The MSCs from the different sources were characterized morphologically, phenotypically, and functionally. Adherence and trilineage differentiation potential were presented in the ovine MSCs. These cell populations highly positively expressed MSC-associated specific markers, namely CD29, CD44, and CD166, but lacked CD31 and CD45 expressions. The BA-MSCs had higher clonogenic and proliferative potentials than the FA-MSCs. The BA-MSCs also showed higher osteogenic and chondrogenic potentials, but lower adipogenic capacity than the FA-MSCs. In addition, the BA-MSCs demonstrated higher chondrogenic, but lower osteogenic capacity than the BM-MSCs. Our study suggests that inhibition of the osteogenic and chondrogenic differentiations of MSCs might be a promising strategy for preventing bony ankylosis in the future.