• Title/Summary/Keyword: FUS

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Acid sphingomyelinase inhibition improves motor behavioral deficits and neuronal loss in an amyotrophic lateral sclerosis mouse model

  • Byung Jo, Choi;Kang Ho, Park;Min Hee, Park;Eric Jinsheng, Huang;Seung Hyun, Kim;Jae-sung, Bae;Hee Kyung, Jin
    • BMB Reports
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    • v.55 no.12
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    • pp.621-626
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    • 2022
  • Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the degeneration of motor neurons in the spinal cord. Main symptoms are manifested as weakness, muscle loss, and muscle atrophy. Some studies have reported that alterations in sphingolipid metabolism may be intimately related to neurodegenerative diseases, including ALS. Acid sphingomyelinase (ASM), a sphingolipid-metabolizing enzyme, is considered an important mediator of neurodegenerative diseases. Herein, we show that ASM activity increases in samples from patients with ALS and in a mouse model. Moreover, genetic inhibition of ASM improves motor function impairment and spinal neuronal loss in an ALS mouse model. Therefore, these results suggest the role of ASM as a potentially effective target and ASM inhibition may be a possible therapeutic approach for ALS.

Proteomic Analysis of Proteins Increased or Reduced by Ethanol of Lactobacillus plantarum ST4 Isolated from Makgeolli, Traditional Korean Rice Wine

  • Lee, Seung-Gyu;Lee, Kang-Wook;Park, Tae-Heung;Park, Ji-Yeong;Han, Nam-Soo;Kim, Jeong-Hwan
    • Journal of Microbiology and Biotechnology
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    • v.22 no.4
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    • pp.516-525
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    • 2012
  • LAB were isolated from makgeolli locally produced around Jinju, Gyeongnam, S. Korea during spring of 2011. Randomly selected 11 isolates from MRS agar plates were identified first by API CHL 50 kits and then 16S rRNA gene sequencing. All 11 isolates were identified as Lactobacillus plantarum. Among them, ST4 grew in MRS broth with ethanol up to 10%, showing the highest alcohol resistance. L. plantarum ST4 was moderately resistant against acid and bile salts. When cellular proteins of L. plantarum ST4 under ethanol stress were analyzed by two-dimensional gel electrophoresis (2DE), the intensities of 6 spots increased, whereas 22 spots decreased at least 2-fold. Those 28 spots were identified by peptide mass fingerprinting (PMF). FusA2 (elongation factor G) increased 18.8-fold (6% ethanol) compared with control. Other proteins were AtpD (ATP synthase subunit beta), DnaK, GroEL, Tuf (elongation factor Tu), and Npr2 (NADH peroxidase), respectively. Among the 22 proteins decreased in intensities, lactate dehydrogenases (LdhD and LdhL1) were included.

Role of MAPK Signaling Pathways in Regulating the Hydrophobin Cryparin in the Chestnut Blight Fungus Cryphonectria parasitica

  • So, Kum-Kang;Kim, Dae-Hyuk
    • Mycobiology
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    • v.45 no.4
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    • pp.362-369
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    • 2017
  • We assessed the regulation of cryparin, a class II hydrophobin, using three representative mitogen-activated protein kinase (MAPK) pathways in Cryphonectria parasitica. Mutation of the CpSlt2 gene, an ortholog of yeast SLT2 in the cell wall integrity (CWI) pathway, resulted in a dramatic decrease in cryparin production. Similarly, a mutant of the CpBck1 gene, a MAP kinase kinase kinase gene in the CWI pathway, showed decreased cryparin production. Additionally, mutation of the cpmk1 gene, an ortholog of yeast HOG1, showed decreased cryparin production. However, mutation of the cpmk2 gene, an ortholog of yeast Kss1/Fus3, showed increased cryparin production. The easy-wet phenotype and accumulation of the cryparin transcript in corresponding mutants were consistent with the cryparin production results. In silico analysis of the promoter region of the cryparin gene revealed the presence of binding motifs related to downstream transcription factors of CWI, HOG1, and pheromone responsive pathways including MADS-box- and Ste12-binding domains. Real-time reverse transcriptase PCR analyses indicated that both CpRlm1, an ortholog of yeast RLM1 in the CWI pathway, and cpst12, an ortholog of yeast STE12 in the mating pathway, showed significantly reduced transcription levels in the mutant strains showing lower cryparin production in C. prasitica. However, the transcription of CpMcm1, an ortholog of yeast MCM1, did not correlate with that of the mutant strains showing downregulation of cryparin. These results indicate that three representative MAPK pathways played a role in regulating cryparin production. However, regulation varied depending on the MAPK pathways: the CWI and HOG1 pathways were stimulatory, whereas the pheromone-responsive MAPK was repressive.

The Performance Analysis of Distributed Reorder Buffer in Superscalar Processor using Analytical Model (해석적 모델을 이용한 분산된 리오더 버퍼 슈퍼스칼라 프로세서의 성능분석)

  • Yoon, Wan-Oh;Shin, Kwang-Sik;Kim, Kyeong-Seob;Lee, Yun-Sub;Choi, Sang-Bang
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.45 no.12
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    • pp.73-82
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    • 2008
  • There are several approaches for reducing the ROB(Reorder Buffer) complexity in processors. The one technique that makes the simplest ROB ports relies on a distributed implementation that spreads the centralized ROB structure across the functional units(FUs). Each distributed buffers are decided on the size of them by workload of the functional units. The performance of the processor depends on the size of distributed ROB. However, most of previous works have depended on the simulation results to decide the optimsize of distributed ROB. In this Paper, we use an analytical model based on the M/M/1 Queuing theory to determine the optimum size of each distributed ROB. Our schemes are evaluated by using the simulation performed by the CPU2000 benchmarks. We are able to choose the optimum size of distributed ROB showing the 99.2% performance compared with existing superscalar processors. We can save 82% hardware resources in ports and reduce more than 30% of delay when ROB and distributed ROB proposed in this paper are designed by HDL.