• 제목/요약/키워드: G2019S

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Polyubiquitin-Proteasomal Degradation of Leucine-Rich Repeat Kinase 2 Wildtype and G2019S

  • Park, Sangwook
    • 대한의생명과학회지
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    • 제27권3호
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    • pp.182-186
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    • 2021
  • Parkinson disease (PD) is becoming one of the most neurodegenerative disorder worldwide. The deposited aggregates have been connected in the pathophysiology of PD, which are degraded either by ubiquitin-proteasomal system (UPS) or autophagy-lysosomal pathway (ALP). Leucin-rich repeat kinase 2 (LRRK2), one of the neurodegenerative proteins of PD is also stringently controlled by both UPS and ALP degradation as well. However, the polyubiquitination pattern of LRRK2 aggregates is largely unknown. Here, we found that K63-linked polyubiquitinations of G2019S mutant, most familial variant for PD, is highly enhanced compared to those of wild type LRRK2 (WT). In addition, in the presence of overexpressed p62/SQSTM-1, ubiquitination of LRRK2 WT or D1994A was reduced, whereas G2019S mutant was not diminished significantly. Therefore, we propose that degradation of G2019S via UPS is more involved with K63-linked ubiquitination than K48-linked ubiquitination, and overexpressed p62/SQSTM-1 does not enhance degradative effect on G2019S variant.

Matrix Metalloproteinase-8 Inhibitor Ameliorates Inflammatory Responses and Behavioral Deficits in LRRK2 G2019S Parkinson's Disease Model Mice

  • Kim, Taewoo;Jeon, Jeha;Park, Jin-Sun;Park, Yeongwon;Kim, Jooeui;Noh, Haneul;Kim, Hee-Sun;Seo, Hyemyung
    • Biomolecules & Therapeutics
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    • 제29권5호
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    • pp.483-491
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    • 2021
  • Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

Some Cycle and Star Related Nordhaus-Gaddum Type Relations on Strong Efficient Dominating Sets

  • Murugan, Karthikeyan
    • Kyungpook Mathematical Journal
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    • 제59권3호
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    • pp.363-375
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    • 2019
  • Let G = (V, E) be a simple graph with p vertices and q edges. A subset S of V (G) is called a strong (weak) efficient dominating set of G if for every $v{\in}V(G)$ we have ${\mid}N_s[v]{\cap}S{\mid}=1$ (resp. ${\mid}N_w[v]{\cap}S{\mid}=1$), where $N_s(v)=\{u{\in}V(G):uv{\in}E(G),\;deg(u){\geq}deg(v)\}$. The minimum cardinality of a strong (weak) efficient dominating set of G is called the strong (weak) efficient domination number of G and is denoted by ${\gamma}_{se}(G)$ (${\gamma}_{we}(G)$). A graph G is strong efficient if there exists a strong efficient dominating set of G. In this paper, some cycle and star related Nordhaus-Gaddum type relations on strong efficient dominating sets and the number of strong efficient dominating sets are studied.

5G URLLC 기술 동향 (Technical Trends of Ultra-Reliable Low-Latency Communication for 5G)

  • 박옥선;김석기;박기윤;신우람;신재승
    • 전자통신동향분석
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    • 제34권6호
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    • pp.42-50
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    • 2019
  • The fifth generation (5G) wireless technology is expected to be the trigger for the fourth industrial revolution. In particular, 5G ultra reliable low latency communication (URLLC) is expected to lead the wireless automation in vertical domains. In this paper, we analyze use cases, key metrics, and physical layer technologies for 5G URLLC standardized in $3^{rd}$ Generation Partnership Project Radio Access Network (3GPP RAN). Additionally, we discuss enabling RAN technologies towards beyond 5G to support high reliability and low latency.

독일 5G주파수 최근(2019) 경매사례 분석 (Latest 5G Spectrum Auction in Germany)

  • 김헌진;이성준
    • 전자통신동향분석
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    • 제34권6호
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    • pp.17-27
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    • 2019
  • This paper introduces the 5G spectrum auction in Germany that occurred last summer and ended overheatedly after an extraordinarily long period. We describe the context of the latest German spectrum auction and trace the participants' bidding behavior. This case details the trend of the 5G spectrum auction and the factors that affect the spectrum auction as follows: First, it is determined that investment obligations that force network installations can be a financial burden to mobile network operators (MNOs) and require a careful approach. Second, excess demands can cause auction overheating and the spectrum supply volume needs to be determined by a proper demand forecast and investment incentive. Third, 'Set-Aside' for local usage aids in developing the vertical industry; however it limits the spectrum supply for mobiles and leads to higher bidding prices. Fourth, a modified adoption of a typical spectrum auction can alleviate MNO's financial burdens to secure the broadband spectrum. Finally, competition to secure the necessary bandwidth in the situation of limited spectrum supply may delay the process of the spectrum auction, causing it overheated.

명란의 등급별 관능적 및 이화학적 품질 특성 비교 (Comparisons of the Sensory and Physicochemical Characterizations of Alaska Pollock Theragra chalcogramma Roe by Grade)

  • 정효빈;차장우;윤인성;이정석;허민수;정은정;김진수
    • 한국수산과학회지
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    • 제52권3호
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    • pp.199-208
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    • 2019
  • The present study compared the sensory and physicochemical characterizations of Alaska pollock Theragra chalcogramma roe according to the L, M, S, 2S, KA, KB, KC, and G grades. The mean weights of the Alaska pollock roe were 81.2 g (74.1-85.7 g) in the L grade, 48.4 g (41.1-54.8 g) in the M grade, 38.6 g (33.5-45.6 g) in the S grade, 29.3 g (25.7-34.2 g) in the 2S grade, 45.7 g (41.4-50.0 g) in the KA grade, 41.4 g (37.7-46.1 g) in the KB grade, 38.3 g (36.0-42.6 g) in the KC grade, and 15.0 g (14.2-15.6 g) in the G grade. The results of the sensory (transparency, physical damage, texture, and odor) and physicochemical (moisture, amino nitrogen and volatile basic nitrogen contents, Hunter redness, and texture) evaluations revealed that, in the normal group, the quality of Alaska pollock roe was highest in the L grade followed by the M, S, and 2S grades whereas, in the cut-group order, the quality was highest in the KA grade followed by the KB, KC, and G grades. The present results suggest that the L, M, S, 2S, KA, and KB grades could be used for high-quality Alaska pollock roe products.

G0/G1 Switch 2 Induces Cell Survival and Metastasis through Integrin-Mediated Signal Transduction in Human Invasive Breast Cancer Cells

  • Cho, Eunah;Kwon, Yeo-Jung;Ye, Dong-Jin;Baek, Hyoung-Seok;Kwon, Tae-Uk;Choi, Hyung-Kyoon;Chun, Young-Jin
    • Biomolecules & Therapeutics
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    • 제27권6호
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    • pp.591-602
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    • 2019
  • Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.