• Title/Summary/Keyword: $S1P_2$

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Pro-Inflammatory Role of S1P3 in Macrophages

  • Heo, Jae-Yeong;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • v.27 no.4
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    • pp.373-380
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    • 2019
  • Sphingosine kinase 1 and its product, sphingosine 1-phosphate (S1P), as well as their receptors, have been implicated in inflammatory responses. The functions of receptors $S1P_1$ and $S1P_2$ on cell motility have been investigated. However, the function of $S1P_3$ has been poorly investigated. In this study, the roles of $S1P_3$ on inflammatory response were investigated in primary peritoneal macrophages. $S1P_3$ receptor was induced along with sphingosine kinase 1 by stimulation of lipopolysaccharide (LPS). LPS treatment induced inflammatory genes, such iNOS, COX-2, $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. TY52156, an antagonist of $S1P_3$ suppressed the induction of inflammatory genes in a concentration dependent manner. Suppression of iNOS and COX-2 induction was further confirmed by western blotting and NO measurement. Suppression of $IL-1{\beta}$ induction was also confirmed by western blotting and ELISA. Caspase 1, which is responsible for $IL-1{\beta}$ production, was similarly induced by LPS and suppressed by TY52156. Therefore, we have shown $S1P_3$ induction in the inflammatory conditions and its pro-inflammatory roles. Targeting $S1P_3$ might be a strategy for regulating inflammatory diseases.

S1P1 Regulates M1/M2 Polarization toward Brain Injury after Transient Focal Cerebral Ischemia

  • Gaire, Bhakta Prasad;Bae, Young Joo;Choi, Ji Woong
    • Biomolecules & Therapeutics
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    • v.27 no.6
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    • pp.522-529
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    • 2019
  • M1/M2 polarization of immune cells including microglia has been well characterized. It mediates detrimental or beneficial roles in neuroinflammatory disorders including cerebral ischemia. We have previously found that sphingosine 1-phospate receptor subtype 1 ($S1P_1$) in post-ischemic brain following transient middle cerebral artery occlusion (tMCAO) can trigger microglial activation, leading to brain damage. Although the link between $S1P_1$ and microglial activation as a pathogenesis in cerebral ischemia had been clearly demonstrated, whether the pathogenic role of $S1P_1$ is associated with its regulation of M1/M2 polarization remains unclear. Thus, this study aimed to determine whether $S1P_1$ was associated with regulation of M1/M2 polarization in post-ischemic brain. Suppressing $S1P_1$ activity with its functional antagonist, AUY954 (5 mg/kg, p.o.), attenuated mRNA upregulation of M1 polarization markers in post-ischemic brain at 1 day and 3 days after tMCAO challenge. Similarly, suppressing $S1P_1$ activity with AUY954 administration inhibited M1-polarizatioin-relevant $NF-{\kappa}B$ activation in post-ischemic brain. Particularly, $NF-{\kappa}B$ activation was observed in activated microglia of post-ischemic brain and markedly attenuated by AUY954, indicating that M1 polarization through $S1P_1$ in post-ischemic brain mainly occurred in activated microglia. Suppressing $S1P_1$ activity with AUY954 also increased mRNA expression levels of M2 polarization markers in post-ischemic brain, further indicating that $S1P_1$ could also influence M2 polarization in post-ischemic brain. Finally, suppressing $S1P_1$ activity decreased phosphorylation of M1-relevant ERK1/2, p38, and JNK MAPKs, but increased phosphorylation of M2-relevant Akt, all of which were downstream pathways following $S1P_1$ activation. Overall, these results revealed $S1P_1$-regulated M1/M2 polarization toward brain damage as a pathogenesis of cerebral ischemia.

Synthesis of Nucleophilic Adducts of Thiols (Ⅰ). Addition of Cysteine to $\beta$-Nitrostyrene Derivatives

  • Kim, Tae-Rin;Choi, Sung-Yong
    • Bulletin of the Korean Chemical Society
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    • v.2 no.4
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    • pp.125-129
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    • 1981
  • The addition reactions of cysteine without blocking amino and carboxyl groups to substituted and unsubstituted ${\beta}$-nitro-styrene derivatives were investigated. ${\beta}$-Nitrostyrene(1a), p-methyl-${\beta}$-nitrostyrene(1b), 3,4,5-trimethoxy-$[\beta}$ -nitrostyrene(1c), $[\varpi}$-3,4-methylenedioxy-${\beta}$ -nitrostyrene(1d), o-, m- and p-chloro-${\beta}$ -nitrostyrene (1e, 1f, 1g) and o-, m- and p-methoxy-${\beta}$-nitrostyrene (1h, 1i, 1j) easily undergo addition reactions with cysteine to form S-(2-nitro-1-phenylethyl)-L-cysteine(3a), S-[2-nitro-1-(p-methyl)phenyl-ethyl]-L-cysteine(3b), S-[2-nitro-1-(3',4',5'-trimethoxy) phenylethyl]-L-cysteine(3c), S-[2-nitro-1-($[\vatpi}$ -3',4'-methylenedioxy)phenylethyl]-L-cysteine(3d), S-[2-nitro-1-(o-chloro)phenylethyl]-L-cysteine(3e), S-[2-nitro-1-(m-chloro)-phenylethyl]-L-cysteine(3f), S-[2-nitro-1-(p-chloro)phenylethyl]-L-cysteine(3g), S-[2-nitro-1-(o-methoxy)phenylethyl]-L-cysteine(3h), S-[2-nitro-1-(m-methoxy)phenylethyl]-L-cysteine(3i) and S-[2-nitro-1-(p-methoxy)phenylethyl]-L-cysteine(3j), respectively. The structure of adducts were confirmed by means of UV-spectrum, IR-spectrum, molecular weight measurement and elemental analysis. The various factors effecting the yield of cysteine adducts to ${\beta}$-nitrostyrene derivatives were also studied.

Zur Valenz deutscher verbaler Somatismen mit der Komponente ${\lceil}hand{\rfloor}$ (독일어의 신체부위 "손" 관련 관용구의 결합가 연구)

  • Kim Soo-Nam
    • Koreanishche Zeitschrift fur Deutsche Sprachwissenschaft
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    • v.4
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    • pp.1-27
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    • 2001
  • 이 글의 목적은 독일어 신체어휘 관련 관용구들 가운데 ${\lceil}$Duden Band 11${\rfloor}$에 수록된 108개의 $\lceil$$\rfloor$ 관련 관용구를 대상으로 이들의 형태$\cdot$통사구조를 파악하고, 그들을 모형화하는 것이다. 우리는 연구 대상을 문장에서 결합가 보유어로서 술어의 기능을 하는 관용구에 한정했다. 우리는 $\lceil$$\rfloor$ 관련 관용구를 보충어의 수와 형태에 따라 크게 세 가지 부류, 즉 1가, 2가, 3가의 관용구로 구분하였다 보충어의 형태는 명사구(Sn, Sd, Sa)와 전치사구(pS)에 한정했으며 문장형태의 보충어, 예를 들어 부문장(NS)과 부정사문(Inf) 형태는 고려하지 않았다. 이들이 보충어로 간주될 수 있는지의 여부는 아직 더 많은 연구를 필요로 하기 때문에 다음 과제로 남겨두었다. 일차적으로 외적 결합가($\"{a}u{\beta}ere\;Valenz)$에 따라, 이차적으로는 내적 결합가(innere Valenz)에 따라 108개의 $\lceil$$\rfloor$ 관련 관용구를 분석한 결과 우리는 다음과 같은 형태$\cdot$통사적 문형을 얻을 수 있었다. $\cdot$ 1가 동사 관용구: 1) PL-Sn : (1) PL[VPL - Sa] - Sn (2) PL(VPL - pS) - Sn (3) PL[VPL - Sa - pS] - Sn (4) PL[VPL - pS - pS] - Sn Sondergruppen: PL[VPL - Sa - Inf] - Sn PL[VPL - pS - Inf] - Sn 2) PL - Sd: (1) PL[VPL - Sn] - Sd (2) PL[VPL - Sn(es) - pS] - Sd $\cdot$ 2가 동사 관용구1) PL - Sn - Sd: (1) PL[VPL - Sa] - Sn - Sd (2) PL[VPL - pS] - Sn - Sd (3) PL[VPL - Sa - pS) - Sn - Sd 2) PL - Sn - pS: (1) PL[VPL - Sa] - Sn - pS (2) PL[VPL - pS] - Sn - pS (3) PL(VPL - Sa - pS) - Sn - pS 3) PL[VPL - pS) - Sn -Sa $\cdot$ 3가 동사 관용구: (1) PL[VPL - pS] - Sn - Sd - Sa (2) PL[VPL - pS] - Sn - Sa - pS (3) PL[VPL - Sa] - Sn - Sd - pS 이러한 분류가 보여주듯이, 독일어에는 1가, 2가, 3가의 관용구가 있으며, 구조 외적으로 동일한 통사적 결합가를 갖는다 하더라도 구조 내적 성분구조가 다르다는 것을 알 수 있다. 우리는 이 글이 외국어로서의 독일어를 배우는 이들에게 독일어의 관용구를 보다 올바르게 이해할 수 있는 방법론적인 토대를 제공함은 물론, (관용어) 사전에서 외국인 학습자를 고려하여 관용구를 알기 쉽게 기술하는 데 도움을 줄 수 있기를 바란다.

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Expression System for Optimal Production of Xylitol Dehydrogenase (XYL2) in Saccharomyces cerevisiae (출아효모에서 xylitol dehydrogenase (XYL2)의 최적 생산을 위한 발현 시스템 구축)

  • Jung, Hoe-Myung;Kim, Yeon-Hee
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1403-1409
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    • 2017
  • In this study, the xylitol dehydrogenase (XYL2) gene was expressed in Saccharomyces cerevisiae as a host cell for ease of use in the degradation of lignocellulosic biomass (xylose). To select suitable expression systems for the S.XYL2 gene from S. cerevisiae and the P.XYL2 gene from Pichia stipitis, $pGMF{\alpha}-S.XYL2$, $pGMF{\alpha}-P.XYL2$, $pAMF{\alpha}-S.XYL2$ and $pAMF{\alpha}-P.XYL2$ plasmids with the GAL10 promoter and ADH1 promoter, respectively, were constructed. The mating factor ${\alpha}$ ($MF{\alpha}$) signal sequence was also connected to each promoter to allow secretion. Each plasmid was transformed into S. cerevisiae $SEY2102{\Delta}trp1$ strain and the xylitol dehydrogenase activity was investigated. The GAL10 promoter proved more suitable than the ADH1 promoter for expression of the XYL2 gene, and the xylitol dehydrogenase activity from P. stipitis was twice that from S. cerevisiae. The xylitol dehydrogenase showed $NAD^+$-dependent activity and about 77% of the recombinant xylitol dehydrogenase was secreted into the periplasmic space of the $SEY2102{\Delta}trp1/pGMF{\alpha}-P.XYL2$ strain. The xylitol dehydrogenase activity was increased by up to 41% when a glucose/xylose mixture was supplied as a carbon source, rather than glucose alone. The expression system and culture conditions optimized in this study resulted in large amounts of xylitol dehydrogenase using S. cerevisiae as the host strain, indicating the potential of this expression system for use in bioethanol production and industrial applications.

Sphingosine-1-Phosphate-Induced Migration and Differentiation of Human Mesenchymal Stem Cells to Smooth Muscle Cells (Sphingosine-1-phosphate에 의한 중간엽 줄기세포의 이동과 평활근세포로의 분화)

  • Song, Hae-Young;Shin, Sang-Hun;Kim, Min-Young;Kim, Jae-Ho
    • Journal of Life Science
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    • v.21 no.2
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    • pp.183-193
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    • 2011
  • Migration and differentiation of mesenchymal stem cells are crucial for tissue regeneration in response to injury. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a variety of biological processes, including proliferation, survival, differentiation and motility. In the present study, we determined the role of S1P in migration and differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs). S1P stimulated migration of BMSCs in a dose- and time-dependent manner, and pre-incubation of the cells with pertussis toxin completely abrogated S1P-induced migration, suggesting involvement of Gi-coupled receptors in S1P-induced cell migration. S1P elicited elevation of intracellular concentration of $Ca^{2+}$ ($[Ca^{2+}]_i$) and pretreatment with VPC23019, an antagonist of $S1P_1/S1P_3$, blocked S1P-induced migration and increase of $[Ca^{2+}]_i$. Small interfering RNA-mediated knockdown of endogenous $S1P_1$ attenuated S1P-induced migration of BMSCs. Furthermore, S1P treatment induced expression of $\alpha$-smooth muscle actin ($\alpha$-SMA), a smooth muscle marker, and pretreatment with VPC23019 abrogated S1P-induced $\alpha$-SMA expression. S1P induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), and pretreatment of cells with SB202190, an inhibitor of p38 MAPK, or adenoviral overexpression of a dominant-negative mutant of the p38 MAPK blocked S1P-induced cell migration and $\alpha$-SMA expression. Taken together, these results suggest that S1P stimulates migration and smooth muscle differentiation of BMSCs through an $S1P_1$-p38 MAPK-dependent mechanism.

Synthesis of Nucleophilic Adducts of Thiols (Ⅳ). Addition of Glutathione to $\beta$-Nitrostyrene Derivatives

  • Kim, Tae-Rin;Choi, Sung-Yong;Choi, Won-Sik
    • Bulletin of the Korean Chemical Society
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    • v.4 no.2
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    • pp.92-95
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    • 1983
  • The addition products of glutathione to ${\beta}$ -nitrostyrene derivatives were synthesized. ${\beta}$ -Nitrostyrene (1a), p-methyl-${\beta}$-nitrostyrene (1b), 3,4,5-trimethoxy-${\beta}$-nitrostyrene (1c), o-, m- and p-chloro-${\beta}$-nitrostyrene (1e, 1f, 1g) and o-, m- and p-methoxy-${\beta}$-nitrostyrene (1h, 1i, 1j) undergo addition reactions with glutathione to form S-(2-nitro-1-phenylethyl)-L-glutathione (5a), S-[2-nitro-1-(p-methyl)phenylethyl]-L-glutatione (5b), S-[2-nitro-1-(3', 4', 5'-trimethoxy)phenylethyl]-L-glutathione (5c), S-[2-nitro-1-(o-chloro)phenylethyl]-L-glutathione (5e), S-[2-nitro-1-(m-choro)phenylethyl]-L-glutathione (5f), S-[2-nitro-1-(p-chloro)phenylethyl]-L-glutathione (5g), S-[2-nitro-x-(o-methoxy)-phenylethyl]-L-glutathion e(5h), S-[2-nitro-x-(m-methoxy)phenylethyl]-L-glutathion e (5i), and S-[2-nitro-1-(p-methoxy)phenylethy])-L-glutathione (5j), respectively. The structure of adducts were identified by UV and IR-spectra, molecular weight measurement, and elemental analysis.

A NEW CHARACTERIZATION OF ALTERNATING AND SYMMETRIC GROUPS

  • ALAVI S. H.;DANESHKHAW A.
    • Journal of applied mathematics & informatics
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    • v.17 no.1_2_3
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    • pp.245-258
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    • 2005
  • In this paper we prove that the alternating groups A_n, for n = p, p+1, p+2 and symmetric groups $S_n$, for n = p, p+1, where p$\ge$3 is a prime number, can be uniquely determined by their order components. As one of the important consequence of this characterization we show that the simple groups An, where n = p, p+1, P+2 and p$\ge$3 is prime, satisfy in Thompson's conjecture and Shi's conjecture.

An Analytic Study on factors Affecting the School Nurse's Activities in Daegu City and Kyungpook Province (대구.경북지역 일부 양호교사의 업무수행에 미치는 요인분석)

  • Gwak, Oh-Gae
    • Research in Community and Public Health Nursing
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    • v.1 no.1
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    • pp.503-517
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    • 1989
  • This study is to analyze factors affecting the school nurse's activities. The survey was undertaken during Sept. 1-Nov. 30, 1986. The subjects were 137 school nurses from elementary, junior-high, and senior-high schools in Daegu City and Kyungppk Province. The results are as follows: 1. Correlational findings between school nurse's self-confidence and their general characteristics 1) Program Planning & Evaluation: Health Experinece(r=-0.1803, p<0.05) Salary Step(r=-0.1741, p<0.05) 2) Clinic Management: Salary STep(r=-0.2580, p<0.01) 3) Health Education: Salary Step(r=-0.1929, p<0.05) 4) Management of School Environment: Salary Step(r=-0.2501, p<.05) 5) Health Care Services: Health Experience(r=0.1901, p<0.05) Salary Step(r=-0.2424, p<0.05) 2. The degrees of school nurse's self-confidence(high: 4 point, low: 1 point) 1) Clinic Management: 2.92 2) Health Education: 2.86. 3) Program Planning & Evaluation: 2.74 4) Health Care Services: 2.73 5) Management of School Environment: 2.67 6) Operating of School Health Organization: 2.42 3. Significances to self-confidence on school nurse's activities 1) Program Planning as Evaluation: Expending Times for Health Care Services (r=-0.2262, p<0.05) Expending Times for Health Education (r=0.2943, p<0.05) Size of Clinic(r=0.2163, p<0.05) Location of Clinic(t=2.43, gH0.047) Use of Clinic(t=2.06, p<0.007) 2) Clinic Management: Location of Clinic (t=3.36, p<0.010) 3) Health Education: Purchase of Medicine(r=-0.1736, p<0.05) No, of Classes (r=-0.1794, p<0.05) (4) Management of School Environment: School Health Budget(r=0.1731, p<0.05) Home Message(r=0.1805, p<0.05) Location of Clinic(t=4.46, p<0.0001) 5) Operating of School Health Organization: School Health Budget(r=0.1878, p<0.05) Use of Clinic(t:1.90, p<0.018) 6) Health Care Services: School Health Budget(r=1.90, p<0.018) Expending Times for Health Education(r=0.2577, p<0.05) Size of Clinic(r=0.4336, p<0.001) Location of Clinic(t:5.10, p<0.001)

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MONOTONICITY PROPERTIES OF THE GENERALIZED STRUVE FUNCTIONS

  • Ali, Rosihan M.;Mondal, Saiful R.;Nisar, Kottakkaran S.
    • Journal of the Korean Mathematical Society
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    • v.54 no.2
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    • pp.575-598
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    • 2017
  • This paper introduces and studies a generalization of the classical Struve function of order p given by $$_aS_{p,c}(x):=\sum\limits_{k=0}^{\infty}\frac{(-c)^k}{{\Gamma}(ak+p+\frac{3}{2}){\Gamma}(k+\frac{3}{2})}(\frac{x}{2})^{2k+p+1}$$. Representation formulae are derived for $_aS_{p,c}$. Further the function $_aS_{p,c}$ is shown to be a solution of an (a + 1)-order differential equation. Monotonicity and log-convexity properties for the generalized Struve function $_aS_{p,c}$ are investigated, particulary for the case c = -1. As a consequence, $Tur{\acute{a}}n$-type inequalities are established. For a = 2 and c = -1, dominant and subordinant functions are obtained for the Struve function $_2S_{p,-1}$.