• Title/Summary/Keyword: FUS

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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.

Profiles of Non-aureus Staphylococci in Retail Pork and Slaughterhouse Carcasses: Prevalence, Antimicrobial Resistance, and Genetic Determinant of Fusidic Acid Resistance

  • Yang, Yu Jin;Lee, Gi Yong;Kim, Sun Do;Park, Ji Heon;Lee, Soo In;Kim, Geun-Bae;Yang, Soo-Jin
    • Food Science of Animal Resources
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    • v.42 no.2
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    • pp.225-239
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    • 2022
  • As commensal colonizers in livestock, there has been little attention on staphylococci, especially non-aureus staphylococci (NAS), contaminating meat production chain. To assess prevalence of staphylococci in retail pork and slaughterhouse carcass samples in Korea, we collected 578 samples from Korean slaughterhouses (n=311) and retail markets (n=267) for isolation of staphylococci and determined antimicrobial resistance phenotypes in all the isolates. The presence of and prevalence of fusB-family genes (fusB, fusC, fusD, and fusF) and mutations in fusA genes were examined in fusidic acid resistant isolates. A total of 47 staphylococcal isolates of 4 different species (Staphylococcus aureus, n=4; S. hyicus, n=1; S. epidermidis, n=10; Mammaliicoccus sciuri, n=32) were isolated. Fusidic acid resistance were confirmed in 9/10 S. epidermidis and all of the 32 M. sciuri (previously S. sciuri) isolates. Acquired fusidic acid resistance genes were detected in all the resistant strains; fusB and fusC in S. epidermidis and fusB/C in M. sciuri. Multi-locus sequence type analysis revealed that ST63 (n=10, 31%) and ST30 (n=8, 25%) genotypes were most prevalent among fusidic acid resistant M. sciuri isolates. In conclusion, the high prevalence of fusB-family genes in S. epidermidis and M. sciuri strains isolated from pork indicated that NAS might act as a reservoir for fusidic acid resistance gene transmissions in pork production chains.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

  • Lee, Eun Jung;Fomenko, Anton;Lozano, Andres M.
    • Journal of Korean Neurosurgical Society
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    • v.62 no.1
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    • pp.10-26
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    • 2019
  • Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

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.

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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Magnetic Resonance-Guided Focused Ultrasound in Neurosurgery: Taking Lessons from the Past to Inform the Future

  • Jung, Na Young;Chang, Jin Woo
    • Journal of Korean Medical Science
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    • v.33 no.44
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    • pp.279.1-279.16
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    • 2018
  • Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.

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.

Noninvasive Rx of Breast Cancer by MR-guided High Intensity Focused Ultrasound

  • Moonen, Chrit
    • Proceedings of the KSMRM Conference
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    • 2005.09a
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    • pp.77-78
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    • 2005
  • A specific FUS-MRI platform was designed for breast cancer treatment. phased array technologies, sideways FUS transmission, and spatio-temporal temperature control in the complete region of interest, were combined for a novel therapy approach with enhanced safety and afficacy. A phase I clinical trial will start soon.

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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.