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      • KCI등재
      • SCOPUSKCI등재

        Production of Useful Secondary Metabolites in Plants : Functional Genomics Approaches

        Liu, Jang Ryol,Choi, Dong-Woong,Chung, Hwa-Jee,Woo, Sung-Sick 한국식물학회 2002 Journal of Plant Biology Vol.45 No.1

        The paradigm of biological research has been changed by recent developments in genomics, high-throughput biology, and bioinformatics. Conventional biology often was based on empirical, labor-intensive, and time-consuming methods. In the new paradigm, biological research e is driven by a holistic approach on the basis of rational, automatic, and high-throughput methods. New functional compounds can be discovered by using high-throughput screening systems. Secondary metabolite pathways and the genes involved in those pathways are then determined by studying functional genomics in conjunction with the data-mining tools of bioinformatics. In addition, these advances in metabolic engineering enable researchers to confer new secondary metabolic pathways to crops by transferring three to five, or more, heterologous genes taken from various other species. In the future, engineering for the production of useful compounds will be designed by a set of software tools that allows the user to specify a cell's genes, proteins, and other molecules, as well as their individual interactions.

      • Homeobox protein Hhex negatively regulates Treg cells by inhibiting Foxp3 expression and function

        Jang, Sung Woong,Hwang, Soo Seok,Kim, Hyeong Su,Kim, Min Kyung,Lee, Woo Ho,Hwang, Soh Un,Gwak, Jinu,Yew, Si Kyoung,Flavell, Richard A.,Lee, Gap Ryol National Academy of Sciences 2019 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.116 No.51

        <P><B>Significance</B></P><P>Regulatory T (Treg) cells play an essential role in maintaining immune homeostasis. Studying factors that control Treg differentiation and function are critically important to understand immune homeostasis. In this manuscript, we discovered that transcription factor Hhex exerts an inhibitory effect on Treg cell differentiation and function. Hhex-overexpressing Treg cells lose their Foxp3 expression and fail to suppress immune responses. Hhex directly binds to Foxp3 protein and the <I>Foxp3</I> locus and inhibits expression of Foxp3 and its target genes. Thus, Hhex plays an essential role in inhibiting Treg cell differentiation and function via inhibition of Foxp3. This study will benefit clinical research in developing a therapeutic strategy for Treg cell-related diseases.</P><P>Regulatory T (Treg) cells play an essential role in maintaining immune homeostasis, but the suppressive function of Treg cells can be an obstacle in the treatment of cancer and chronic infectious diseases. Here, we identified the homeobox protein Hhex as a negative regulator of Treg cells. The expression of Hhex was lower in Treg cells than in conventional T (Tconv) cells. Hhex expression was repressed in Treg cells by TGF-β/Smad3 signaling. Retroviral overexpression of Hhex inhibited the differentiation of induced Treg (iTreg) cells and the stability of thymic Treg (tTreg) cells by significantly reducing Foxp3 expression. Moreover, Hhex-overexpressing Treg cells lost their immunosuppressive activity and failed to prevent colitis in a mouse model of inflammatory bowel disease (IBD). <I>Hhex</I> expression was increased; however, <I>Foxp3</I> expression was decreased in Treg cells in a delayed-type hypersensitivity (DTH) reaction, a type I immune reaction. Hhex directly bound to the promoters of <I>Foxp3</I> and other Treg signature genes, including <I>Il2ra</I> and <I>Ctla4</I>, and repressed their transactivation. The homeodomain and N-terminal repression domain of Hhex were critical for inhibiting Foxp3 and other Treg signature genes. Thus, Hhex plays an essential role in inhibiting Treg cell differentiation and function via inhibition of Foxp3.</P>

      • SCOPUSKCI등재

        Casein kinase 2 is a critical determinant of the balance of Th17 and Treg cell differentiation

        Jang, Sung Woong,Hwang, Soo Seok,Kim, Hyeong Su,Lee, Keoung Oh,Kim, Min Kyung,Lee, Wonyong,Kim, Kiwan,Lee, Gap Ryol Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.9

        <P>Th17 cells promote inflammatory reactions, whereas regulatory T (Treg) cells inhibit them. Thus, the Th17/Treg cell balance is critically important in inflammatory diseases. However, the molecular mechanisms underlying this balance are unclear. Here, we demonstrate that casein kinase 2 (CK2) is a critical determinant of the Th17/Treg cell balance. Both the inhibition of CK2 with a specific pharmacological inhibitor, CX-4945, and its small hairpin RNA (shRNA)-mediated knockdown suppressed Th17 cell differentiation but reciprocally induced Treg cell differentiation <I>in vitro</I>. Moreover, CX-4945 ameliorated the symptoms of experimental autoimmune encephalomyelitis and reduced Th17 cell infiltration into the central nervous system. Mechanistically, CX-4945 inhibited the IL-6/STAT3 and Akt/mTOR signaling pathways. Thus, CK2 has a crucial role in regulating the Th17/Treg balance.</P>

      • SCOPUSKCI등재

        인삼 ( Panax ginseng C. A. Meyer ) 의 성숙한 배 (胚)로부터 체세포 배발생을 (胚發生) 통한 재분화 및 유식물체의 개화

        이행순(Haeng Soon Lee),이광웅(Kwang Woong Lee),양승균(Seung Gyun Yang),전재흥(Jae Heung Jeon),유장열(Jang Ryol Liu) 한국식물학회 1989 Journal of Plant Biology Vol.32 No.3

        Mature zygotic embryos dissected from ginseng(Panax ginseng C.A. Meyer) seeds were cultured on Murashige and Skoog`s (MS) medium containing various concentrations of 2,4-dichlorophenoxyacetic acid(2,4-D) and kinetin. Somatic embryos were induced directly from cotyledonary tissue or from intervening callus. The induction frequency of somatic embryos was up to 55%. Upon transfer to half-strength MS medium supplemented with 1 ㎎/l 6-benzyladenine(BA) and 1 ㎎/l GA_3, most somatic embryos dveloped into plantlets. Over 50% of the plantlets flowered after 4 weeks of culture and then a few bore immature fruits in vitro. Therefore, it is suggested that the juvenility of the ginseng tissue which give rise to somatic embryos does not interfere with in vitro flowering of their regenerated plantlets.

      • SCOPUSKCI등재

        생장조절제에 의한 인삼 ( Panax ginseng C. A. Meyer ) 의 기내 (器內) 화아형성 (花芽形成) 조절

        이행순(Haeng Soon Lee),이광웅(Kwang Woong Lee),양승균(Seung Gyun Yang),유장열(Jang Ryol Liu) 한국식물학회 1989 Journal of Plant Biology Vol.32 No.4

        Ginseng zygotic embryos, seedlings, and excised cotyledonary nodes were cultured on Murashige and Skoog`s(MS) medium, supplemented with 6-benzyladenine(Ba) and gibberellic acid(GA_3) to induce flower buds. As the concentration of nitrogen compounds in MS medium was reduced to half of its strength, the flowering frequency of zygotic embryos increased up to 90%. The optimum concentration of sucrose in the medium for flowering of seedlings was 30-60 g/l. In all cases flower buds were formed on elongated axillary branches from the cotyledonary node, while the apices remained vegetative. When zygotic embryos and excised cotyledonary nodes were cultured on the medium, supplemented with all possible combinations of BA, GA_3, and abscisic acid(ABA) of 5 μM each, flowering was induced on the medium with either BA, BA+GA_3, or BA+GA_3+ABA. However, when seedlings were employed, flowering was induced on the medium with either BA, BA+GA_3, BA+ABA, or BA+GA_3+ABA. In addition, inclusion of 5 μM indole-3-acetic acid(IAA) in the above combinations did not affect flowering. These results suggest that cytokinins, gibberellins, and inhibitors play primary, permissive, and preventive roles, respectively, in the induction of flowering of ginseng.

      • SCISCIESCOPUS

        PTEN drives Th17 cell differentiation by preventing IL-2 production

        Kim, Hyeong Su,Jang, Sung Woong,Lee, Wonyong,Kim, Kiwan,Sohn, Hyogon,Hwang, Soo Seok,Lee, Gap Ryol The Rockefeller University Press 2017 The Journal of experimental medicine Vol.214 No.11

        <▼1><P>Th17 cells mediate inflammation and autoimmunity. Although it was known that cytokine IL-2 inhibits Th17 cell differentiation, how it does so was elusive. Using IL-17–specific PTEN-deficient mice, Kim et al. show that phosphatase PTEN inhibits IL-2 production and thus promotes Th17 cell differentiation.</P></▼1><▼2><P>T helper 17 (Th17) cells are a CD4<SUP>+</SUP> T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a key factor that regulates Th17 cell differentiation by suppressing IL-2 production. Th17-specific <I>Pten</I> deletion (<I>Pten<SUP>fl/fl</SUP>Il17a<SUP>cre</SUP></I>) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, <I>Pten</I> deficiency up-regulates IL-2 and phosphorylation of STAT5, but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation. PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model. Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2 expression.</P></▼2>

      • KCI등재

        더덕의 체세포배발생에서 전형층분화와 자엽수의 관계

        최필선,소웅영,조덕이,유장렬,Choi Pil-Son,Soh Woong-Young,Cho Duck-Yee,Liu Jang-Ryol 한국식물생명공학회 2005 식물생명공학회지 Vol.32 No.2

        Embryogenic callus was obtained from cotyledonary explants of Codonopsis lanceloata on Murashige & Skoog's medium supplemented with 1 mg/L 2,4-D. Suspension cultures of the embryogenic calli were grown on a shaker at 100 strokes/min, and then the calli were subcultured for 2 weeks in 2,4-D-free medium to produce somatic embryo. In somatic embryos at the globular stage, cotyledon initials began to differentiate themselves in the near distal end of the procambial strand. Dicotyledons, tricotyledon, tetracotyledon and fused cotyledon were differentiated from the distal ends of two, three, four and circular procambial strands, respectively. Nearly circular procambial strand in lower hypocotyls were independently differentiated into two, three, four procambial tissues at cotyledonary node and cotyledons to form somatic embryos with dicotyledon, tricotyledon, tetracotyledon. If the distal subepidermal cells of globular embryo exclusively became cotyledon initials, the torpedo or cotyledonary embryo was characterized by somatic embryos with fused cotyledon. 더덕 자엽절편을 1 mg/L 2,4-D가 첨가된 MS기본배지에 배양하여 배발생캘러스를 얻었고, 호르몬이 첨가되지 않은 MS액체배지에서 구형기의 체세포배를 얻었다. 구형기에서 초기 심장형기로 발달할 때 자엽의 시원세포는 전형성층조직으로부터 분화되기 시작 하였으며, 하배축에서 관찰되는 원통형 전형성층대는 2개의 자엽을 형성할 경우 2개의 전형성층대가, 3개의 자엽은 3개의 전형성층대가, 4개의 자엽은 4개의 전형층대가 각각 독립적으로 분화되어 자엽절과 자엽부위까지 연결되어 있었다. 만약 구형기 체세포배에서 자엽시원세포가 원통형으로 분화될 경우 합생자엽을 갖는 체세포배가 형성되었다.

      • Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation.

        Hwang, Soo Seok,Kim, Young Uk,Lee, Sumin,Jang, Sung Woong,Kim, Min Kyung,Koh, Byung Hee,Lee, Wonyong,Kim, Joomyeong,Souabni, Abdallah,Busslinger, Meinrad,Lee, Gap Ryol National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.1

        <P>The Th2 locus control region (LCR) has been shown to be important in efficient and coordinated cytokine gene regulation during Th2 cell differentiation. However, the molecular mechanism for this is poorly understood. To study the molecular mechanism of the Th2 LCR, we searched for proteins binding to it. We discovered that transcription factor YY1 bound to the LCR and the entire Th2 cytokine locus in a Th2-specific manner. Retroviral overexpression of YY1 induced Th2 cytokine expression. CD4-specific knockdown of YY1 in mice caused marked reduction in Th2 cytokine expression, repressed chromatin remodeling, decreased intrachromosomal interactions, and resistance in an animal model of asthma. YY1 physically associated with GATA-binding protein-3 (GATA3) and is required for GATA3 binding to the locus. YY1 bound to the regulatory elements in the locus before GATA3 binding. Thus, YY1 cooperates with GATA3 and is required for regulation of the Th2 cytokine locus and Th2 cell differentiation.</P>

      • Gene expression profiling of kidneys from Sprague-Dawley rats following 12-week inhalation exposure to silver nanoparticles

        Dong, Mi Sook,Choi, Ji-Yoon,Sung, Jae Hyuck,Kim, Jin Sik,Song, Kyung Seuk,Ryu, Hyun Ryol,Lee, Ji Hyun,Bang, In Seok,An, Kangho,Park, Hyun Min,Song, Nam Woong,Yu, Il Je Informa Healthcare USA, Inc. 2013 Toxicology mechanisms and methods Vol.23 No.6

        <P>The specific properties of silver nanoparticles (AgNPs), such as antimicrobial activity and electrical conductivity, allow them to be used in many fields. However, their expanding application is also raising health, environmental and safety concerns. Previous <I>in vivo</I> AgNP toxicity studies have indicated a gender-different accumulation of silver in the kidneys, with 2-3 times more silver in female kidneys compared to male kidneys. However, no other studies have further addressed this gender difference. Accordingly, the current study investigated the gender-dependent effect of AgNPs on the kidney gene level based on toxicogenomic studies of kidneys obtained from rats exposed to AgNPs via inhalation for 12 weeks. When compared with the fresh air control, the silver nanoparticle-exposed kidneys included 104 genes with a more than 1.3-fold expression increase. For the male rat kidneys exposed to a low or high dose of silver nanoparticles, 96 genes exhibited expression changes, where six genes changed with both the low and high dose; four increased and two decreased. Meanwhile, for the female rat kidneys exposed to a low or high dose of silver nanoparticles, 66 genes exhibited expression changes, where 11 genes changed with both the low and high dose; nine increased and two decreased. Gender-dependent gene expression changes of more than 2-fold were linked to 163 genes, with 79 genes in the male kidneys and 84 genes in the female kidneys, plus gender-dependent gene expression changes of more than 5-fold were linked to 21 genes. However, no genes involved in apoptosis or the cell cycle were activated by the 12-week silver nanoparticle inhalation exposure. Overall, the male rat kidneys showed a higher expression of genes involved in xenobiotic metabolism, while the female rat kidneys showed a higher expression of genes involved in extracellular signaling.</P>

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