• Title/Summary/Keyword: Fus3

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Analysis of domain required for aggregates formation of ALS (Amyotrophic lateral sclerosis)/FTD (Frontotemporal dementia)-linked FUS in mammalian cells (루게릭병 및 전측두엽성 치매 연관 단백질 Fused in Sarcoma (FUS)의 스트레스 응집체 형성에 관여하는 도메인 분석)

  • Jun, Mi-Hee;Lee, Jin-A
    • Analytical Science and Technology
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    • v.28 no.5
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    • pp.331-340
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    • 2015
  • Mutations in Fused in Sarcoma (FUS) have been identified in patients with amyotrophic lateral sclerosis (ALS) or Frontotemporal Dementia (FTD). Pathological FUS is mis-localized to cytosol and forms aggregates associated with stress granules (SG), while FUS is normally localized to nucleus. However, it is largely unknown how pathological FUS forms SG-aggregates and which domains are responsible for this process. In this study, we examined cellular localization and aggregation of ALS-linked FUS missense mutants (P525L, R521C, R521H, R521G), analyzed the domains responsible for cytosolic FUS aggregation in HEK293T cells, and confirmed this in cultured mouse neurons. To do this, we firstly generated missense mutants of FUS and then examined their cellular localization. We found that P525L was mostly mis-localized to cytosol and formed FUS-positive SG aggregates while R521C, R521H, or R521G was localized to both nucleus and cytosol. To further characterize the domains required for aggregate formation of cytosolic FUS, we generated different domain-deletion mutants using FUS-∆17 which has a deletion of nuclear localization signal. Interestingly, cytosolic FUS without SYGQ and RGG1 domain or cytosolic FUS without RGG2-ZnF-RGG3 domain did not form FUS-positive SG aggregates, while cytosolic FUS without RRM domain generated more aggregates compared to FUS-∆17. Taken together, these data suggest that SYGQ-RGG1 or RGG2-ZnF-RGG3 domain contributes to formation of cytosolic aggregate, while RRM domain might interfere with FUS aggregation. Therefore, our studies will provide important insight for understanding cellular pathogenesis of neurodegeneration associated with FUS aggregate as well as finding therapeutic targets for ALS or FTD.

Fus Expression Patterns in Developing Tooth

  • Kim, Eun-Jung;Lee, Jong-Min;Jung, Han-Sung
    • Development and Reproduction
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    • v.17 no.3
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    • pp.215-220
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    • 2013
  • Recently, the RNA/DNA-binding protein FUS, Fused in sarcoma, was shown to play a role in growth, differentiation, and morphogenesis in vertebrates. Because little is known about Fus, we investigated its expression pattern in murine tooth development. In situ hybridization of mouse mandibles at specific developmental stages was performed with a DIG-labeled RNA probe. During early tooth development, Fus was detected in the dental epithelium and dental mesenchyme at 11 days postcoitum (dpc) and 12 dpc. From 14 dpc, Fus was strongly expressed in the dental papilla and the cervical loop of the dental epithelium. At postnatal day 4 (PN4), Fus expression was observed in the odontoblasts, ameloblasts, the proliferation zone of the pulp, and the cervical loop. At PN14, the expression pattern of Fus was found to be maintained in the odontoblasts and the proliferation zone of the pulp. Furthermore, Fus expression was especially strong in the Hertwig's epithelial root sheath (HERS). Therefore, this study suggests that Fus may play a role in the HERS during root development.

The Selective Inhibitory Activity of a Fusaricidin Derivative on a Bloom-Forming Cyanobacterium, Microcystis sp.

  • Ko, So-Ra;Lee, Young-Ki;Srivastava, Ankita;Park, Seung-Hwan;Ahn, Chi-Yong;Oh, Hee-Mock
    • Journal of Microbiology and Biotechnology
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    • v.29 no.1
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    • pp.59-65
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    • 2019
  • Fusaricidin analogs, produced by Paenibacillus polymyxa, were tested for selective control of a major bloom-forming cyanobacterium, Microcystis sp. Fusaricidin (A and B mixtures) and four analogs were isolated from P. polymyxa E681 and investigated for their inhibition of cyanobacterial cell growth. Among the four fusaricidin analogs, fraction 915 Da (designated as Fus901) showed growth inhibition activity for Microcystis aeruginosa but not for Anabaena variabilis and Scenedesmus acutus. Microcystin concentration decreased up to 70% and its content per cell also decreased over 50% after 3 days. Fusaricidin exhibited growth inhibition against Gram-positive bacteria but Fus901 did not. Molecular weights of fusaricidin A and B were 883 Da and 897 Da, whereas that of Fus901 was 915 Da. Structure analysis by a ring-opening method revealed a linear form for Fus901. Expression of the pod gene related to oxidative stress was increased 2.1-fold by Fus901 and that of mcyD decreased up to 40%. These results indicate that Fus901 exerts oxidative stress against M. aeruginosa. Thus, Fus901 can be used as a selective cyanobactericide without disturbing the ecological system and could help in decreasing the microcystin concentration.

Measurement of Internal Temperature Distribution for the Evaluation of Focused Ultrasound (FUS) Stimulation Devices (집속초음파 자극기의 성능평가를 위한 팬텀 내부온도 측정)

  • Doh, Il;Joe, Daniel J.;Kim, Sung Mok;Baik, Kyung Min;Kim, Yong Tae;Park, Seung Min
    • Journal of Biomedical Engineering Research
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    • v.43 no.3
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    • pp.147-152
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    • 2022
  • This research is to measure real-time temperature distribution inside a tissue-mimicking phantom for the safety and effectiveness evaluations of focused ultrasound (FUS) device capable of linear scanning stimulation. Since the focusing area of the FUS stimulation device is smaller than diameter of conventional thermal probe and keeps moving, it is impossible to monitor temperature distribution inside the phantom. By using the phantom with a thin film temperature sensor array inserted, real-time temperature change caused by the FUS device was measured. The translation of the measured temperature peak was also tracked successfully. The present phantom had been experimentally proven to be applicable to validate the performance and safety of the therapeutic ultrasound devices.

A Case Report of the Effect of Paljeongsan on the Female Urethral Syndrome (팔정산가미(八正散加味)로 호전된 여성요도증후군 환자 치험 1례)

  • Kim, Soo-Min;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.20 no.4
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    • pp.225-233
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    • 2007
  • Purpose: The purpose of this study Is to report the effect of Paljeongsangami(八正散加味) on the female urethral syndrome(FUS). Methods: A subject was a 29-year-old woman who suffered from FUS even after the treatment of western medicine. We evaluated the routine blood test. U/A, Pap smear and N.gonorrhoeae PCR, but there were no abnormal findings. We gave her Paljeongsangami 3 times a day for 10 days with acupuncture and moxibustion. During the treatment, we asked her complete a urinary dairy. Results: After the treatment, the symptoms of FUS was disappeared and her condition was maintained for 2 months at least. Conclusion: This case report showed that Paljeongsangami is efficacious for FUS and could prevent chronic progress and relapse of symptoms. More clinical data and studies are to be done for the effective application of the various oriental medicinal therapy on FUS.

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Quantitative Profiling of Dual Phosphorylation of Fus3 MAP Kinase in Saccharomyces cerevisiae

  • Hur, Jae-Young;Kang, Gum-Yong;Choi, Min-Yeon;Jung, Jin Woo;Kim, Kwang-Pyo;Park, Sang-Hyun
    • Molecules and Cells
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    • v.26 no.1
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    • pp.41-47
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    • 2008
  • Mitogen-activated protein kinase (MAPK) signaling is a crucial component of eukaryotic cells; it plays an important role in responses to extracelluar stimuli and in the regulation of various cellular activities. The signaling cascade is evolutionarily conserved in the eukaryotic kingdom from yeast to human. In response to a variety of extracellular signals, MAPK activity is known to be regulated via phosphorylation of a conserved $T{\times}Y$ motif at the activation loop in which both threonine and tyrosine residues are phosphorylated by the upstream kinase. However, the mechanism by which both residues are phosphorylated continues to remain elusive. In the budding yeast, Saccharomyces cerevisiae, Fus3 MAPK is involved in the mating signaling pathway. In order to elucidate the functional mechanism of MAPK activation, we quantitatively profiled phosphorylation of the $T{\times}Y$ motif in Fus3 using mass spectrometry (MS). We used synthetic heavy stable isotope-labeled phosphopeptides and nonphosphopeptides corresponding to the proteolytic $T{\times}Y$ motif of Fus3 and accompanying data-dependent tandem MS to quantitatively monitor dynamic changes in the phosphorylation events of MAPK. Phosphospecific immunoblotting and the MS data suggested that the tyrosine residue is dynamically phosphorylated upon stimulation and that this leads to dual phosphorylation. In contrast, the magnitude of threonine phosphorylation did not change significantly. However, the absence of a threonine residue leads to hyperphosphorylation of the tyrosine residue in the unstimulated condition, suggesting that the threonine residue contributes to the control of signaling noise.

Efficient Token Flow Design for the MPEG RMC Framework

  • Cui, Li;Kim, Sowon;Kim, Hyungyu;Jang, Euee S.
    • IEIE Transactions on Smart Processing and Computing
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    • v.3 no.5
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    • pp.251-258
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    • 2014
  • This paper proposes an efficient token flow design methodology for a decoder in the MPEG Reconfigurable Media Coding (RMC) framework. The MPEG RMC framework facilitates a decoder to be configured with a set of modules called functional units (FUs) that are connected by tokens. Such a modular design philosophy of the MPEG RMC framework enables the reusability and reconfigurability of FUs. One drawback of the MPEG RMC framework is that the decoder performance can be affected by increasing the token transmissions between FUs. The proposed method improves the design of the FU network in the RMC framework toward real-time decoder implementation. In the proposed method, the merging of FU, the separation of token flow, and the merging of token transactions are applied to minimize the token traffic between FUs. The experimental results of the MPEG-4 SP decoder show that the proposed method reduces the total decoding time by up to 77 percent compared to the design of the RMC simulation model.

Substrate Specificity of the Yeast Protein Tyrosine Phosphatase, PTP1, Overexpressed from an Escherichia coli Expression System

  • Kwon, Mi-Yun;Oh, Min-Su;Han, Jun-Pil;Cho, Hyeong-Jin
    • BMB Reports
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    • v.29 no.4
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    • pp.386-392
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    • 1996
  • A Saccharomyces cerevisiae Protein Tyrosine Phosphatase, PTP1, was expressed from an Escherichia coli expression system and milligram quantities of active PTP1 were purified chromatographically. The substrate specificity of the recombinant PTP1 was probed using synthetic phosphotyrosine-containing peptides corresponding to the regulatory phosphorylation sites of the yeast MAP kinase homologues $Fus3_{176-186}$, $Kss1_{179-189}$, and $Hog1_{170-180}$. Peptide sequences derived from the MAP kinase homologues were chosen arbitrarily as starting points for sequence variation studies even though they are not likely to be candidates for physiological substrates of PTP1. Phosphotyrosyl-$Hog1_{170-180}$ peptide showed a $K_M$ value of 877 ${\mu}M$ and phosphorylated $Kss1_{179-189}$ and $Fus3_{176-186}$ peptides showed lower $K_M$ values of 74 ${\mu}M$ and 51 ${\mu}M$ each. To study the effect of sequence variations of the peptide, amino acids of the undecapeptide $Hog1_{170-180}$ (DPQMTGpYVSTR) were sequentially substituted by an alanine residue. More extensive variations of each amino acid revealed positional importance of each amino acid residue. Based on these results, we derived a peptide sequence (DADEpYDA) that is recognized by PTP1 with an affinity ($K_M$ is 4 ${\mu}M$) significantly higher than that of the peptides derived from the phosphorylation sites of Fus3, Kss1, and Hog1.

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The Mitogen-Activated Protein Kinase Signal Transduction Pathways in Alternaria Species

  • Xu, Houjuan;Xu, Xiaoxue;Wang, Yu-Jun;Bajpai, Vivek K.;Huang, Lisha;Chen, Yongfang;Baek, Kwang-Hyun
    • The Plant Pathology Journal
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    • v.28 no.3
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    • pp.227-238
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    • 2012
  • Mitogen-activated protein kinase (MAPK) cascades are conserved signaling modules in the eukaryotic cells. They are involved in many major cell processes in fungi such as stress responses, vegetative growth, pathogenicity, secondary metabolism and cell wall integrity. In this review, we summarized the advances of research on the MAPK signaling pathways in Alternaria species. As major phytopathogenic fungi, Alternaria species reduce crop production. In contrast to the five MAPK pathways known in yeast, only three MAPK pathways as Fus3/Kss1-type, Hog1-type, and Slt2-type have been characterized in Alternaria. The Fus3/Kss1-type MAPK pathway participates in regulation of vegetative growth, conidiation, production of some cell-wall-degrading enzymes and pathogenicity. The Hog1-type pathway is involved in osmotic and oxidative stress, fungicides susceptibility and pathogenicity. The Slt2-type MAP kinases play an important role on maintaining cell wall integrity, pathogenicity and conidiation. Although recent advances on the MAPK pathways in Alternaria spp. reveal many important features on the pathogenicity, there are many unsolved problems regarding to the unknown MAP kinase cascade components and network among other major signal transduction. Considering the economic loss induced by Alternaria spp., more researches on the MAPK pathways will need to control the Alternaria diseases.

Magnetic Resonance Imaging: Historical Overview, Technical Developments, and Clinical Applications

  • Jahng, Geon-Ho;Park, Soonchan;Ryu, Chang-Woo;Cho, Zang-Hee
    • Progress in Medical Physics
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    • v.31 no.3
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    • pp.35-53
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    • 2020
  • The authors congratulate the cerebrations for the 30 years of the Korean Society of Medical Physics (http://www.ksmp.or.kr/). The paper is published to recognize the anniversary. Geon-Ho Jahng invited Professor Z. H. Cho to join to submit this manuscript because he has been one of the leaders in the field of magnetic resonance imaging (MRI) during the last 40 years. In this review, we describe the development and clinical histories of MRI internationally and domestically. We also discuss diffusion and perfusion MRI, molecular imaging using MRI and MR spectroscopy (MRS), and the hybrid systems, such as positron emission tomography-MRI (PET-MRI), MR-guided focused ultrasound surgery (MRgFUS), and MRI-guided linear accelerators (MRI-LINACs). In each part, we discuss the historical evolution of the developments, technical developments, and clinical applications.