• Title/Summary/Keyword: Nuclear localization

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HDAC4 Regulates Muscle Fiber Type-Specific Gene Expression Programs

  • Cohen, Todd J.;Choi, Moon-Chang;Kapur, Meghan;Lira, Vitor A.;Yan, Zhen;Yao, Tso-Pang
    • Molecules and Cells
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    • v.38 no.4
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    • pp.343-348
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    • 2015
  • Fiber type-specific programs controlled by the transcription factor MEF2 dictate muscle functionality. Here, we show that HDAC4, a potent MEF2 inhibitor, is predominantly localized to the nuclei in fast/glycolytic fibers in contrast to the sarcoplasm in slow/oxidative fibers. The cytoplasmic localization is associated with HDAC4 hyper-phosphorylation in slow/oxidative-fibers. Genetic reprogramming of fast/glycolytic fibers to oxidative fibers by active CaMKII or calcineurin leads to increased HDAC4 phosphorylation, HDAC4 nuclear export, and an increase in markers associated with oxidative fibers. Indeed, HDAC4 represses the MEF2-dependent, PGC-$1{\alpha}$-mediated oxidative metabolic gene program. Thus differential phosphorylation and localization of HDAC4 contributes to establishing fiber type-specific transcriptional programs.

Source Localization Technique for Metallic Impact Source by Using Phase Delay between Different Type Sensors (다종 센서간 위상 차이를 이용한 충격 위치추정 기법)

  • Choi, Kyoung-Sik;Choi, Young-Chul;Park, Jin-Ho;Kim, Whan-Woo
    • Transactions of the Korean Society for Noise and Vibration Engineering
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    • v.18 no.11
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    • pp.1143-1149
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    • 2008
  • In a nuclear power plant, loose part monitoring and its diagnostic technique is one of the major issues for ensuring the structural integrity of the reactor system. Typically, accelerometers are mounted on the surface of a reactor vessel to localize impact location cavsed by the impact of metallic substances on the reactor system. However, in some cases, the number of the accelerometers is not enough to estimate the impact location precisely. In such a case, one of alternative plan is to utilize another type sensors that can measure the vibration of the reactor structure even though the measuring frequency ranges are different from each others. The AE sensors installed on the reactor structure can be utilized as additional sensors for loose part monitoring. In this paper, we proposed a new method to estimate impact location by using both accelerometer signal and AE signal, simultaneously. The feasibility of the proposed method is verified by an experiment. The experimental results demonstrate that we can enhance the reliability and precision of the loose part monitoring.

Vinyl-Stilbene Inhibits Human Norovirus RNA Replication by Activating Heat-Shock Factor-1

  • Lee, Ahrim;Sung, Jieun;Harmalkar, Dipesh S.;Kang, Hyeseul;Lee, Hwayoung;Lee, Kyeong;Lee, Choongho
    • Biomolecules & Therapeutics
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    • v.30 no.1
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    • pp.64-71
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    • 2022
  • Norovirus (NV) is the most common cause of viral gastroenteritis, with the potential to develop into a fatal disease in those who are immuno-compromised, and effective vaccines and treatments are still non-existent. In this study, we aimed to elucidate the molecular mechanism of the previously identified NV replication inhibitor utilizing a vinyl-stilbene backbone, AC-1858. First, we confirmed the inhibition of the NV RNA replication by a structural analog of AC-1858, AC-2288 with its exclusive cytoplasmic sub-cellular localization. We further validated the induction of one specific host factor, the phosphorylated form of heat shock factor (HSF)-1, and its increased nuclear localization by AC-1858 treatment. Finally, we verified the positive and negative impact of the siRNA-mediated downregulation and lentivirus-mediated overexpression of HSF-1 on NV RNA replication. In conclusion, these data suggest the restrictive role of the host factor HSF-1 in overall viral RNA genome replication during the NV life cycle.

Genetic localization of epicoccamide biosynthetic gene cluster in Epicoccum nigrum KACC 40642

  • Choi, Eun Ha;Park, Si-Hyung;Kwon, Hyung-Jin
    • Journal of Applied Biological Chemistry
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    • v.65 no.3
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    • pp.159-166
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    • 2022
  • Epicoccum nigrum produces epipyrone A (orevactaene), a yellow polyketide pigment. Its biosynthetic gene cluster was previously characterized in E. nigrum KACC 40642. The YES liquid culture of this strain revealed high-level production of epicoccamide (EPC), with an identity that was determined using liquid chromatography-mass spectrometry analysis and molecular mass search using the SuperNatural database V2 webserver. The production of EPC was further confirmed by compound isolation and nuclear magnetic resonance spectroscopy. EPC is a highly reduced polyketide with tetramic acid and mannosyl moieties. The EPC structure guided us to localize the hypothetical EPC biosynthetic gene cluster (BGC) in E. nigrum ICMP 19927 genome sequence. The BGC contains genes encoding highly reducing (HR)-fungal polyketide synthase (fPKS)-nonribosomal peptide synthetase (NRPS), glycosyltransferase (GT), enoylreductase, cytochrome P450, and N-methyltrasnferase. Targeted inactivation of the HR-fPKS-NRPS and GT genes abolished EPC production, supporting the successful localization of EPC BGC. This study provides a platform to explore the hidden biological activities of EPC, a bolaamphiphilic compound.

Ligand-Independent Activation of the Androgen Receptor by Insulin-Like Growth Factor-I and the Role of the MAPK Pathway in Skeletal Muscle Cells

  • Kim, Hye Jin;Lee, Won Jun
    • Molecules and Cells
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    • v.28 no.6
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    • pp.589-593
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    • 2009
  • In this study, the roles of the p38 MAPK, ERK1/2 and JNK signaling pathway in IGF-I-induced AR induction and activation were examined. C2C12 cells were treated with IGF-I in the absence or presence of various inhibitors of p38 MAPK (SB203580), ERK1/2 (PD98059), and JNK (SP600125). Inhibition of the MAPK pathway with SB203580, PD98059, or SP600125 significantly decreased IGF-I-induced AR phosphorylation and total AR protein expression. IGF-I-induced nuclear fraction of total AR and phosphorylated AR were significantly inhibited by SB203580, PD98059, or SP600125. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by those inhibitors in dose-dependent manner. Confocal images showed that IGF-I-induced AR nuclear translocation from cytosol was significantly blocked by SB203580, PD98059, or SP600125, suggesting that the MAPK pathway regulates IGF-I-induced AR nuclear localization in skeletal muscle cells. The present results suggest that the MAPK pathways are required for the ligand-independent activation of AR by IGF-I in C2C12 skeletal muscle cells.

Experience for Development and Capacity Certification of Safety Relief Valves (안전방출밸브 개발과 용량인증 사례)

  • Kim, Chil-Sung;Roh, Hee-Seon;Kim, Kang-Tae;Kim, Ji-Heon;Kim, Jong-Su
    • The KSFM Journal of Fluid Machinery
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    • v.8 no.3 s.30
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    • pp.16-25
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    • 2005
  • The purpose of this study is localization of safety relief valves for Nuclear Service. The safety relief valve is the important equipment used to protect the pressure vessel, the steam generator and the other pressure facility from overpressure by discharging the operating medium when the pressure of system is reaching the design pressure of the system. We developed design technology used FEM ' CFM about safety relief valve for Nuclear Service according to ASME (or KEPIC) Code and KHNP's Technical Specification. To prove validity of a design technology, actually, we manufactured and inspected and tested the sample products designed according to a developed technology. The capacity qualification test was achieved according to requirement of ASME(or KEPIC) Code by NBBI and the functional qualification test was achieved according to ASME QME-1 for operating condition in technical specification of KHNP by NLI. Therefore we have to achieve the development of safety relief valves for Nuclear Service with our own technologies.

Brain Hypoxia Imaging (뇌 저산소증 영상)

  • Song, Ho-Chun
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.2
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    • pp.91-96
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    • 2007
  • The measurement of pathologically low levels of tissue $pO_2$ is an important diagnostic goal for determining the prognosis of many clinically important diseases including cardiovascular insufficiency, stroke and cancer. The target tissues nowaday have mostly been tumors or the myocardium, with less attention centered on the brain. Radiolabelled nitroimidazole or derivatives may be useful in identifying the hypoxic cells in cerebrovascular disease or traumatic brain injury, and hypoxic-ischemic encephalopathy. In acute stroke, the target of therapy is the severely hypoxic but salvageable tissue. $^{18}F-MISO$ PET and $^{99}mTc-EC-metronidazole$ SPECT in patients with acute ischemic stroke identified hypoxic tissues and ischemic penumbra, and predicted its outcome. A study using $^{123}I-IAZA$ in patient with closed head injury detected the hypoxic tissues after head injury. Up till now these radiopharmaceuticals have drawbacks due to its relatively low concentration with hypoxic tissues associated with/without low blood-brain barrier permeability and the necessity to wait a long time to achieve acceptable target to background ratios for imaging in acute ischemic stroke. It is needed to develop new hypoxic marker exhibiting more rapid localization in the hypoxic region in the brain. And then, the hypoxic brain imaging with imidazoles or non-imidazoles may be very useful in detecting the hypoxic tissues, determining therapeutic strategies and developing therapeutic drugs in several neurological disease, especially, in acute ischemic stroke.

Review of Radionuclide Treatment for Neuroendocrine Tumors (신경내분비종양의 방사성핵종 치료)

  • Jeong, Hwan-Jeong
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.2
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    • pp.90-95
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    • 2006
  • Neuroendocrine tumors (NETs) consist of a heterogeneous group of tumors that are able to uptake neuroamine and/or specific receptors, such as somatostatin receptors, which can play important roles of the localization and treatment of these tumors. When considering therapy with radionuclides, the best radioligand should be carefully investigated. $^{131}I$-MIBG and beta-particle emitter labeled somatostatin analogs are well established radionuclide therapy modalities for NETs. $^{111}In,\;^{90}Y\;and\;^{177}Lu$ radiolabeled somatostatin analogues have been used for treatment of NETs. Further, radionuclide therapy modalities, for example, radioimmunotherapy, radiolabeled peptides such as minigastrin are currently under development and in different phases of clinical investigation. for all radionuclides used for therapy, long-term and survival statistics are not yet available and only partial tumour responses have been obtained using $^{131}I$-MIBG and $^{111}In$-octreotide. Experimental results using $^{90}Y$-DOTA-lanreotide as well as $^{90}Y-DOTA-D-Phe1-Tyr^3-octreotide$ and/or $^{177}Lu-DOTA-Tyr^3-octreotate$ have indicated the possible clinical potential of radionuclides receptor-targeted radiotherapy it may be hoped that the efficacy of radionuclide therapy will be improved by co-administration of chemotherapeutic drugs whose antitumoral properties may be synergistic with that of irradiation.

Localization of Klotho in cisplatin induced acute kidney failure (Cisplatin 유도 급성신부전에서 Klotho 단백질의 발현)

  • Park, So-Ra;Kim, Tae-Won;Kim, Young-Jung;Kim, Hyun-Tae;Ryu, Si-Yun;Jung, Ju-Young
    • Korean Journal of Veterinary Research
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    • v.54 no.4
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    • pp.225-231
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    • 2014
  • Klotho deficiency is an early event in acute kidney injury (AKI) that exacerbates acute kidney damage. The present study explored the expression of Klotho and inflammation related factors in cisplatin-induced AKI. Rats (n = 18) were treated with cisplatin intraperitoneal injection (5 mg/kg) or left untreated as controls (n = 6), then sacrificed at 5 (n = 6) and 10 days (n = 6) treatment. Five days after cisplatin injection, the serum kidney enzymes and kidney cell apoptosis were significantly increased. Moreover, the expression of Klotho was decreased when compared to the control group, especially in the cortex and outer medulla regions. In contrast, inflammation related signals including nuclear factor kappa B, tumor necrosis factor-${\alpha}$, and tumor necrosis factor-like weak inducer of apoptosis were enhanced. However, 10 days after cisplatin injection, Klotho expression was enhanced upon both IHC and Western blot analysis, with slightly recovered renal function and decreased apoptosis. Furthermore, inflammation related signals expression was decreased relative to the 5 days group. Overall, this study confirmed the opposite expression patterns between Klotho and inflammation related signals and their localization in cisplatin-induced AKI kidney.

The Study on Function and Localization of Nup97 in Fission Yeast (분열효모에서 Nup97의 기능과 세포 내 위치에 대한 연구)

  • Hwang, Duk-Kyung;Yoon, Jin-Ho
    • Korean Journal of Microbiology
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    • v.44 no.2
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    • pp.105-109
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    • 2008
  • We studied on the function and localization of fission yeast Schizosaccharomyces pombe Nup97p, which is homologous to nucleoporin Nic96p in budding yeast Saccharomyces cerevisiae. There was no effect on growth and $poly(A)^{+}$ RNA distribution of cells when nup97 gene was overexpressed. However, the haploid ${\Delta}nup97::kan^{r}$ null mutants confirmed extensive $poly(A)^{+}$ RNA accumulation in the nucleus, abnormal DNA distribution, and cessation of growth when nup97 expression was repressed. We determined the subcellular localization of Nup97 tagged at the N terminus or the C terminus with GFP. Both fusions complemented growth defect of ${\Delta}nup97::kan^{r}$ null mutants. An integrated version of the nup97-GFP fusion was constructed at the nup97 locus. Nup97-GFP fusions expressed from its own promoter was localized at the nuclear periphery with a punctate appearance. These results suggest that Nup97p in fission yeast is also nucleoporin, which is involved in mRNA export.