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      • Analysis of the Endoplasmic Reticulum Subproteome in the Livers of Type 2 Diabetic Mice

        Park, Edmond Changkyun,Kim, Gun-Hwa,Yun, Sung-Ho,Lim, Hye Li,Hong, Yeonhee,Kwon, Sang-Oh,Kwon, Joseph,Chung, Young-Ho,Kim, Seung Il Molecular Diversity Preservation International (MD 2012 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.13 No.12

        <P>Type 2 diabetes is a chronic metabolic disease that results from insulin resistance in the liver, muscle, and adipose tissue and relative insulin deficiency. The endoplasmic reticulum (ER) plays a crucial role in the regulation of the cellular response to insulin. Recently, ER stress has been known to reduce the insulin sensitivity of the liver and lead to type 2 diabetes. However, detailed mechanisms of ER stress response that leads to type 2 diabetes remains unknown. To obtain a global view of ER function in type 2 diabetic liver and identify proteins that may be responsible for hepatic ER stress and insulin resistance, we performed proteomics analysis of mouse liver ER using nano UPLC-MS<SUP>E</SUP>. A total of 1584 proteins were identified in control C57 and type 2 diabetic <I>db/db</I> mice livers. Comparison of the rER and sER proteomes from normal mice showed that proteins involved in protein synthesis and metabolic process were enriched in the rER, while those associated with transport and cellular homeostasis were localized to the sER. In addition, proteins involved in protein folding and ER stress were found only in the rER. In the livers of <I>db/db</I> mice, however, the functions of the rER and sER were severely disrupted, including the capacity to resolve ER stress. These results provide new insight into the research on hepatic insulin resistance and type 2 diabetes and are suggestive of the potential use of the differentially expressed hepatic ER proteins as biomarkers for hepatic insulin resistance and type 2 diabetes.</P>

      • Analysis of the expression of microtubule plus-end tracking proteins (+TIPs) during <i>Xenopus laevis</i> embryogenesis

        Park, Edmond Changkyun,Lee, Hyeyoon,Hong, Yeonhee,Kim, Mi-Jung,Lee, Zee-Won,Kim, Seung Il,Kim, Soohyun,Kim, Gun-Hwa,Han, Jin-Kwan Elsevier 2012 Gene expression patterns Vol.12 No.5

        <P><B>Graphical abstract</B></P><P><ce:figure id='f0040'></ce:figure></P><P><B>Highlights</B></P><P>► We identified novel <I>Xenopus</I> microtubule +TIPs, Clip1, p150<SUP>glued</SUP>, Clasp1, Lis1 and Stim1. ► We examined expression patterns of <I>Xenopus</I> +TIPs during embryogenesis. ► <I>Xenopus</I> +TIPs are expressed in the ectoderm at early stages and in the neural tissues at later stages. ► <I>Xenopus</I> +TIPs are also enriched in the involuting mesoderm during gastrulation.</P> <P><B>Abstract</B></P><P>Microtubules are a component of the cytoskeleton and are important for maintaining cell structure and providing platforms for intracellular transport in diverse cellular processes. Microtubule plus-end tracking proteins (+TIPs), a structurally and functionally diverse group of proteins, are specifically accumulated in the microtubule plus end and regulate dynamic microtubule behavior. We characterized the +TIPs, Clip1, p150<SUP>glued</SUP>, Clasp1, Lis1 and Stim1, in <I>Xenopus laevis</I> and report their expression patterns during embryogenesis in this paper. All the five +TIP genes are maternally expressed and have similar expression patterns during <I>Xenopus</I> embryo development. The expression of +TIPs is localized in the animal hemisphere and ectoderm region at early stages of embryonic development. As development progresses to later stages, the ectodermal expression of +TIPs persists in head and neural tube structures. Clasp1, p150<SUP>glued</SUP> and Lis1 in particular are specifically expressed in the cranial nerves. Importantly, +TIPs are also expressed in the involuting mesoderm during gastrulation. This is the first study of developmental expression patterns of +TIPs, and our analysis provides insight that could serve as the basis for future research of microtubules in vertebrate development, cell movements during gastrulation and neurogenesis.</P>

      • Clinical proteomic analysis of scrub typhus infection

        Park, Edmond Changkyun,Lee, Sang-Yeop,Yun, Sung Ho,Choi, Chi-Won,Lee, Hayoung,Song, Hyun Seok,Jun, Sangmi,Kim, Gun-Hwa,Lee, Chang-Seop,Kim, Seung Il BioMed Central 2018 Clinical proteomics Vol.15 No.1

        <P><B>Background</B></P><P> Scrub typhus is an acute and febrile infectious disease caused by the Gram-negative α-proteobacterium <I>Orientia tsutsugamushi</I> from the family Rickettsiaceae that is widely distributed in Northern, Southern and Eastern Asia. In the present study, we analysed the serum proteome of scrub typhus patients to investigate specific clinical protein patterns in an attempt to explain pathophysiology and discover potential biomarkers of infection.</P><P><B>Methods</B></P><P>Serum samples were collected from three patients (before and after treatment with antibiotics) and three healthy subjects. One-dimensional sodium dodecyl sulphate–polyacrylamide gel electrophoresis followed by liquid chromatography-tandem mass spectrometry was performed to identify differentially abundant proteins using quantitative proteomic approaches. Bioinformatic analysis was then performed using Ingenuity Pathway Analysis.</P><P><B>Results</B></P><P>Proteomic analysis identified 236 serum proteins, of which 32 were differentially expressed in normal subjects, naive scrub typhus patients and patients treated with antibiotics. Comparative bioinformatic analysis of the identified proteins revealed up-regulation of proteins involved in immune responses, especially complement system, following infection with <I>O. tsutsugamushi</I>, and normal expression was largely rescued by antibiotic treatment.</P><P><B>Conclusions</B></P><P>This is the first proteomic study of clinical serum samples from scrub typhus patients. Proteomic analysis identified changes in protein expression upon infection with <I>O. tsutsugamushi</I> and following antibiotic treatment. Our results provide valuable information for further investigation of scrub typhus therapy and diagnosis.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1186/s12014-018-9181-5) contains supplementary material, which is available to authorized users.</P>

      • Differential Expression of MicroRNAs in Patients with Glioblastoma after Concomitant Chemoradiotherapy

        Park, Edmond Changkyun,Kim, Giwon,Jung, Jongsun,Wang, KyoungMin,Lee, Sunwoo,Jeon, Sin-Soo,Lee, Zee Won,Kim, Seung Il,Kim, Soohyun,Oh, Young-Taek,Shin, Ju-Hyun,Jang, Hong-Seok,Choi, Byung-Ock,Kim, Gun- Mary Ann Liebert 2013 OMICS Vol.17 No.5

        <P>Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, and notorious for resistance to chemoradiotherapy. MicroRNAs (miRNAs) are significantly involved in the initiation and progression of numerous cancers; however, the role of miRNAs in recurrence of tumors remains unknown. Here we tried to identify novel miRNAs that are differentially expressed in recurrent GBM. Tissue samples were obtained from patients with primary and recurrent GBM treated with chemoradiotherapy, and the expression changes of miRNAs were measured by microarray. A total of 318 miRNAs were expressed in the GBM patients. The expression of 43 miRNAs were significantly altered at least 2-fold in primary and recurrent GBMs. Bioinformatic analysis revealed that the differentially expressed miRNAs and their putative target genes were mainly involved in cell death, cellular development, and cellular growth and proliferation, which are the key regulators for stem cells. Pathway analysis supported that the miRNAs may regulate signaling associated with induction and maintenance of cancer and stem cell, such as p53, ErbB1, Notch, Wnt, and TGF-β signaling pathways. These data suggest that, in recurrent GBM, growth factor and anti-apoptotic signalings for cancer cell growth and proliferation are regulated by miRNAs. Our findings will aid future research in understanding the pathophysiology of recurrent GBM and identifying diagnostic markers and/or therapeutic targets for recurrence of GBM.</P>

      • SCIESCOPUSKCI등재

        Comparison of Digital PCR and Quantitative PCR with Various SARS-CoV-2 Primer-Probe Sets

        ( Changwoo Park ),( Jina Lee ),( Zohaib Ul Hassan ),( Keun Bon Ku ),( Seong-jun Kim ),( Hong Gi Kim ),( Edmond Changkyun Park ),( Gun-soo Park ),( Daeui Park ),( Seung-hwa Baek ),( Dongju Park ),( Jih 한국미생물생명공학회(구 한국산업미생물학회) 2021 Journal of microbiology and biotechnology Vol.31 No.3

        The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) as an international health emergency. Current diagnostic tests are based on the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method, which is the gold standard test that involves the amplification of viral RNA. However, the RT-qPCR assay has limitations in terms of sensitivity and quantification. In this study, we tested both qPCR and droplet digital PCR (ddPCR) to detect low amounts of viral RNA. The cycle threshold (CT) of the viral RNA by RT-PCR significantly varied according to the sequences of the primer and probe sets with in vitro transcript (IVT) RNA or viral RNA as templates, whereas the copy number of the viral RNA by ddPCR was effectively quantified with IVT RNA, cultured viral RNA, and RNA from clinical samples. Furthermore, the clinical samples were assayed via both methods, and the sensitivity of the ddPCR was determined to be equal to or more than that of the RT-qPCR. However, the ddPCR assay is more suitable for determining the copy number of reference materials. These findings suggest that the qPCR assay with the ddPCR defined reference materials could be used as a highly sensitive and compatible diagnostic method for viral RNA detection.

      • Proteomic Characterization of the Outer Membrane Vesicle of <i>Pseudomonas putida</i> KT2440

        Choi, Chi-Won,Park, Edmond Changkyun,Yun, Sung Ho,Lee, Sang-Yeop,Lee, Yeol Gyun,Hong, Yeonhee,Park, Kyeong Ryang,Kim, Sang-Hyun,Kim, Gun-Hwa,Kim, Seung Il American Chemical Society 2014 JOURNAL OF PROTEOME RESEARCH Vol.13 No.10

        <P>Outer membrane vesicles (OMVs) are produced by various pathogenic Gram-negative bacteria such as <I>Escherichia coli</I>, <I>Pseudomonas aeruginosa</I>, and <I>Acinetobacter baumannii</I>. In this study, we isolated OMVs from a representative soil bacterium, <I>Pseudomonas putida</I> KT2440, which has a biodegradative activity toward various aromatic compounds. Proteomic analysis identified the outer membrane proteins (OMPs) OprC, OprD, OprE, OprF, OprH, OprG, and OprW as major components of the OMV of <I>P. putida</I> KT2440. The production of OMVs was dependent on the nutrient availability in the culture media, and the up- or down-regulation of specific OMPs was observed according to the culture conditions. In particular, porins (e.g., benzoate-specific porin, BenF-like porin) and enzymes (e.g., catechol 1,2-dioxygenase, benzoate dioxygenase) for benzoate degradation were uniquely found in OMVs prepared from <I>P. putida</I> KT2440 that were cultured in media containing benzoate as the energy source. OMVs of <I>P. putida</I> KT2440 showed low pathological activity toward cultured cells that originated from human lung cells, which suggests their potential as adjuvants or OMV vaccine carriers. Our results suggest that the protein composition of the OMVs of <I>P. putida</I> KT2440 reflects the characteristics of the total proteome of <I>P. putida</I> KT2440.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2014/jprobs.2014.13.issue-10/pr500411d/production/images/medium/pr-2014-00411d_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr500411d'>ACS Electronic Supporting Info</A></P>

      • Potential Usefulness of <i> Streptococcus pneumoniae</i> Extracellular Membrane Vesicles as Antibacterial Vaccines

        Choi, Chi-Won,Park, Edmond Changkyun,Yun, Sung Ho,Lee, Sang-Yeop,Kim, Seung Il,Kim, Gun-Hwa Hindawi Publishing Corporation 2017 Journal of immunology research Vol.2017 No.-

        <P>The secretion of extracellular membrane vesicles (EMVs) is a common phenomenon that occurs in archaea, bacteria, and mammalian cells. The EMVs of bacteria play important roles in their virulence, biogenesis mechanisms, and host cell interactions. Bacterial EMVs have recently become the focus of attention because of their potential as highly effective vaccines that cause few side effects. Here, we isolated the EMVs of<I> Streptococcus pneumoniae</I> and examined their potential as new vaccine candidates. Although the<I> S. pneumoniae</I> bacteria were highly pathogenic in a mouse model, the EMVs purified from these bacteria showed low pathological activity both in cell culture and in mice. When mice were injected intraperitoneally with<I> S. pneumoniae</I> EMVs and then challenged, they were protected from both the homologous strain and another pathogenic serotype of<I> S. pneumoniae</I>. We also identified a number of proteins that may have immunogenic activity and may be responsible for the immune responses by the hosts. These results suggest that<I> S. pneumoniae</I> EMVs or their individual immunogenic antigens may be useful as new vaccine agents.</P>

      • KCI등재

        Wnt/β-catenin 신호를 조절하는 인산화 효소

        신은영(Eun-Young Shin),박창균(Edmond Changkyun Park),홍연희(Yeonhee Hong),김건화(Gun-Hwa Kim) 한국생명과학회 2013 생명과학회지 Vol.23 No.7

        Wnt/β-catenin 신호는 세포의 운명 결정, 증식, 분화 등을 조절하는 척추 동물 배아 발생과 성체의 항상성 유지에 필수적인 세포신호전달경로이다. 이러한 Wnt/β-catenin의 비정상적인 조절에 의해 선천적 기형, 암, 대사질환 등을 비롯한 다양한 질병이 유발된다. 이를 바탕으로 최근 Wnt/β-catenin 신호의 조절을 통한 암을 비롯한 질병의 치료를 위한 연구가 활발히 진행되고 있다. 따라서 Wnt/β-catenin 신호를 조절하는 인자의 발굴 및 자세한 작용 기전에 대한 연구가 절실히 필요하다. 본 총설에서는 최근 새롭게 알려진 Wnt/β-catenin 신호 조절 기작에 대해 설명하고, 현재까지 알려진 Wnt/β-catenin을 조절하는 인산화 효소(kinase)의 종류와 작용 기전과 새로운 약물 타겟으로 전망을 알아 보고자 한다. The Wnt/β-catenin signaling pathway is an evolutionarily conserved signaling network that is critical for embryonic development and adult tissue maintenance. In addition, aberrant activation of Wnt/β-catenin signaling is implicated in the formation of various human diseases, including cancers. Thus, study of the underlying molecular mechanism of Wnt/β-catenin signaling regulation is important to understand and treat diseases. Inhibition of aberrant Wnt pathway activity in cancer cell lines efficiently blocks their growth, highlighting the great potential of therapeutics designed to achieve this in cancer patients. Recently, protein kinases have emerged as key regulating components of Wnt/β -catenin signaling. In this review, we provide the most recent information on Wnt/β-catenin signaling, describe protein kinases involved in Wnt/β-catenin signaling, and discuss their potential as drug targets.

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