Identification of two rare mutations c.1318G>A and c.6438+2T>G in a Chinese DMD family as genetic markers

Yingchuan Zhu,Lijun Yang,Tengjiao Ma,Yilu Lu,Dachang Tao,Yunqiang Liu,Yongxin Ma 한국유전학회 2020 Genes & Genomics Vol.42 No.9

Background Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder with no efective treatment, which underscores the importance of avoiding the birth of children with DMD by identifying pathogenic mutations and obtaining an accurate prenatal diagnosis. Objective The objective of this study was to analyze the genetic defect of a Chinese family where all male patients have died of DMD. Methods Multiplex ligation dependent probe analysis (MLPA) and next-generation sequencing (NGS) were employed to detect DMD mutations. The candidate mutations were then validated by Sanger sequencing. In vitro splicing assay was further conducted to examine the potential efect of the novel DMD splice site mutation on splicing. Results We found that two rare DMD mutations c.1318G>A and c.6438+2T>G passed from generation to generation among female carriers and they may be used as genetic markers in the Chinese DMD family. In vitro splicing assay further revealed that the novel classical splice site mutation c.6438+2T>G gave rise to a new donor splice site, which resulted in a frame shift of the transcripts and a premature termination at position 2159 in exon 45 (p.Y2144Nfs*16). Conclusion We found that two co-inherited mutations passed from generation to generation in female carriers and they may be used as genetic markers in the Chinese DMD family. Our fndings not only expanded the DMD mutation spectrum, but also provided an important basis for identifying of female carriers and avoiding the birth of afected male children in this DMD family.

CLOCK and BMAL1 stabilize and activate RHOA to promote F-actin formation in cancer cells

Teng-jiao Ma,Zhi-wei Zhang,Yilu Lu,Ying-ying Zhang,Da-chang Tao,Yun-qiang Liu,Yong-xin Ma 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Circadian genes control most of the physiological functions in cancer cells, including cell proliferation, migration, and invasion. The CLOCK and BMAL1 complex plays a central role in circadian rhythms. Previous studies have shown that circadian genes may act as oncogenes or tumor-suppressor genes. In addition, F-actin, regulated by RHOA, has been shown to participate in tumor progression. However, the roles of the CLOCK and BMAL1 genes in the regulation of tumor progression via the RHOA-ROCK-CFL pathway remain largely unclear. Here we first indicate that the rearrangement of F-actin is regulated by CLOCK and BMAL1. We found that CLOCK and BMAL1 can upregulate RHOA expression by inhibiting CUL3-mediated ubiquitination and activate RHOA by reducing the interaction between RHOA and RhoGDI. Consequently, CLOCK and BMAL1 control the expression of the components of the RHOA-ROCK-CFL pathway, which alters the dynamics of F-actin/G-actin turnover and promotes cancer cell proliferation, migration,

A novel NPHS2 mutation (c.865A > G) identified in a Chinese family with steroid-resistant nephrotic syndrome alters subcellular localization of nephrin

Wu Na,Zhu Yingchuan,Jiang Wenhao,Song Yue,Yin Lan,Lu Yilu,Tao Dachang,Liu Yunqiang,Ma Yongxin 한국유전학회 2022 Genes & Genomics Vol.44 No.5

Background: NPHS2 is the causative gene of nephrotic syndrome type 2 (MIM 600995) which often clinically manifests as steroid-resistant nephrotic syndrome (SRNS). The NPHS2 gene encodes a slit diaphragm (SD) associated protein podocin. Objective: This study reported a novel disease-causing mutation of NPHS2 in a Chinese family with SRNS. We also investigated the pathogenic mechanism of the variants in this family. Method: A Chinese family with SRNS was recruited. Whole exome sequencing was performed to screen for disease-causing mutation. Sanger sequencing was used to confirm the results. In vitro functional experiments including immunoblotting, co-immunoprecipitation and double immunofluorescence staining were performed to explore the pathogenic mechanisms of mutations. Results: In this family, compound heterozygous mutations of NPHS2 (c.467dupT and c.865A > G) were identified and segregated with the disease. The maternal c.865A > G was a novel variant, leading to amino acid substitution (p.K289E). In vitro functional assays indicated that c.467dupT (p.L156FfsX11) mutant lost interaction with nephrin. Both K289E and L156FfsX11 mutants showed sharply diminished plasma membrane localization. Furthermore, abnormal distribution of podocin mutants also altered the cell membrane localization of nephrin. Conclusion: We reported a family with SRNS caused by compound heterozygous mutations of NPHS2 (c.467dupT and c.865A > G). c.865A > G (p.K289E) in NPHS2 was a novel causative variant associated with SRNS. Both variants in this family not only affected the normal cell membrane localization of podocin, but also altered the cell membrane localization of nephrin which is the major architectural protein of SD.

ORiginal Article : Endoscopic Intervention through Endoscopic Retrograde Cholangiopancreatography in the Management of Symptomatic Pancreas Divisum: A Long-Term Follow-Up Study

( Yi Lu ),( Bin Xu ),( Lu Chen ),( Li Ke Bie ),( Biao Gong ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of symptomatic pancreas divisum (PD) and to discuss whether ERCP procedures and outcomes in younger patients differ from those of adults. Methods: Symptomatic patients with PD were included in the study and divided into underaged (age ≤17 years) and adult (age ≥18 years) group. The clinical information of each patient was reviewed, and then the patients were contacted by telephone or their medical records were reviewed to determine their long-term followup outcomes. Results: A total of 141 procedures were performed in 82 patients (17 underaged and 65 adult patients). The ERCP indications included abdominal pain (39.02%), pancreatitis (12.20%), recurrent pancreatitis (36.59%), and other discomfort (12.20%). The endoscopic interventions included endoscopic pancreatic sphincterotomy in 44.68% of the patients, bouginage in 26.95%, pancreatic ductal stone extraction in 19.15%, endoscopic nasopancreatic drainage in 21.99%, and endoscopic retrograde pancreatic drainage in 56.74%. After a median follow-up of 41 months, the overall response rate was 62.32%. Between the underaged group and the adult group, significant differences were not observed in the ERCP procedures, complications and longterm follow-up results. Conclusions: ERCP is a safe and effective treatment for symptomatic PD. Based on the details, complications, and follow-up results, the ERCP procedure did not present differences between the underaged and adult groups. (Gut Liver 2016;10:476-482)

Using characteristic strings to derive valid contracted graphs with hexagonal links plus other links for type synthesis of closed mechanisms

Yi Lu,Yang Lu,Nijia Ye,Bingyi Mao,Chunping Sui,Jianda Han 대한기계학회 2012 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.26 No.5

"It has been a significant and challenging issue to derive the complex valid contracted graphs (CGs) with hexagonal links plus other links and identify their isomorphism for creating novel closed mechanisms. This paper focuses on the derivation of the valid CGs with hexagonal links plus other links using the characteristic strings (CSs). First, the concepts on the CGs and CSs are explained, and the numbers of vertices and edges in the CGs are solved. Second, the relative criterion are determined for representing/deriving CGs and identifying isomorphic/invalid CGs by CSs. Third, some simple CGs are derived from some associated linkages with hexagonal links plus more other links, are represented by CSs, and the isomorphic/invalid CGs are identified using the CSs and the isomorphic queues of the links. Fourth, some examples are given for illustrating their applications. Finally, many complex valid CGs with more hexagonal links plus other links are represented and derived using CSs, and their isomorphism are identified using CSs."

Dynamics analysis and workspace of a novel 4-DoF parallel manipulator with multi-couple constrained wrenches

Yi Lu,Yang Liu,Yang Lu,Nijia Ye,Bo Hu 대한기계학회 2018 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.32 No.8

A novel 4-DoF parallel manipulator with multi-couple constrained wrenches is proposed. Its 3D model is constructed and its characteristics, DoF and two couple-constrained wrenched are analyzed. Its kinematic formulae for solving DoF, the displacement, velocity, acceleration, singularities of moving links are derived and analyzed. Its dynamics formulae for solving the dynamic active forces and the dynamic couple-constrained wrench are derived, and its workspace is constructed. Finally, an analytic example is given to demonstrate the solution of the kinematics and dynamics, and the results of analytical solution are verified using a simulation mechanism. This paper is aimed at laying a solid theoretical and technical foundation of development of the parallel manipulators with multi-couple constrained wrenches.

A novel parallel sensor with six rigid compliant limbs for measuring six- component force/torque

Yi Lu,Yongli Wang,Yang Lu 대한기계학회 2019 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.33 No.6

A novel parallel sensor with six rigid/compliant hybrid limbs and six standard force sensors is developed for measuring the sixcomponent force/torque. The measuring theory and performances are studied. A prototype of the robot hybrid hands with the parallel sensor is developed. A prototype of the parallel sensor is built up and its merits and performances are analyzed. A statics equation among the forces of the standard force sensors and the whole external load and a stiffness model of the parallel sensor are established based on its equivalent parallel mechanism. The force/torque of the parallel sensor is measured under the given external load. The theoretical solutions of the statics model of the parallel sensor are obtained and verified by both the experimental measuring solutions of the prototype of the parallel sensor and the simulation solutions of a FE model.

Kinematics/statics analysis of a novel serial-parallel robotic arm with hand

Yi Lu,Zhuohong Dai,Nijia Ye,Peng Wang 대한기계학회 2015 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.29 No.10

A robotic arm with fingered hand generally has multi-functions to complete various complicated operations. A novel serial-parallel roboticarm with a hand is proposed and its kinematics and statics are studied systematically. A 3D prototype of the serial-parallel roboticarm with a hand is constructed and analyzed by simulation. The serial-parallel robotic arm with a hand is composed of an upper 3RPSparallel manipulator, a lower 3SPR parallel manipulator and a hand with three finger mechanisms. Its kinematics formulae for solving thedisplacement, velocity, acceleration of are derived. Its statics formula for solving the active/constrained forces is derived. Its reachableworkspace and orientation workspace are constructed and analyzed. Finally, an analytic example is given for solving the kinematics andstatics of the serial-parallel robotic arm with a hand and the analytic solutions are verified by a simulation mechanism.

FACILE SYNTHESIS OF COPPER NANOPARTICLE CHAINS

YI LU,JIN-KU LIU,XIAO-JUN HU,JIN MU 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2007 NANO Vol.2 No.1

The copper nanoparticle chains have been synthesized through a self-assembly process with sodium polymethacylic acid as the template. The resulted nanoparticle chains were 0.8–1.5 μm long, and the composed nanoparticles were about 30 nm in diameter. The self-assembly formation mechanism has been proposed.

Anti-inflammatory Cembranoids from the Formosan Soft Coral Sinularia discrepans

Yi Lu,Huey-Jen Su,Yung-Husan Chen,Zhi-Hong Wen,Jyh-Horng Sheu,Jui-Hsin Su 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.8

A new cembranoid, discrepanolide A (1), along with four known cembranoids 2-5 were isolated from the Formosan soft coral Sinularia discrepans. The structures of these compounds were determined by analysis of spectroscopic data and by comparison of NMR data with those of known compounds. None of these compounds were found to be cytotoxic towards a limited panel of cancer cell lines. Compounds 3-5 were found to display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Compound 5 also significantly inhibited the accumulation of pro-inflammatory COX-2 protein.