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      • KCI등재

        S100A8 Induces Secretion of MCP-1, IL-6, and IL-8 via TLR4 in Jurkat T Cells

        A Reum Nam,Da Hae Kim,Mun Jeong Kim,Ji-Sook Lee,Seung-Ju Yang,In Sik Kim 대한의생명과학회 2016 Biomedical Science Letters Vol.22 No.2

        In the pathogenesis of inflammatory diseases such as allergies, S100A8 acts as an important molecule and T lymphocytes are essential cytokine-releasing cells. In this study, we investigated the effect of S100A8 on release of cytokines, specifically MCP-1, IL-6, and IL-8 in T cells, and its associated signaling mechanism. S100A8 increased secretion of MCP-1, IL-6, and IL-8 in a time- and dose-dependent manner. Elevated secretion of MCP-1, IL-6, and IL-8 due to S100A8 was inhibited by the TLR4 inhibitor TLR4i, the PI3K inhibitor LY294002, the PKCδ inhibitor rottlerin, the ERK inhibitor PD98059, the p38 MAPK inhibitor SB202190, the JNK inhibitor SP600125, and the NF-κB inhibitor BAY-11-7085. S100A8 induced phosphorylation of ERK, p38 MAPK, and JNK in a time-dependent manner, and activation was suppressed by TLR4i, LY294002, and rottlerin. S100A8 induced NF-κB activation by Iκ-Bα degradation, and NF-κB activity was suppressed by PD98059, SB202190, and SP600125. These results indicate that S100A8 induces cytokine release via TLR4. Study of PI3K, PKCδ, MAPKs, and NF-κB will contribute to elucidation of the S100A8-invovled mechanism.

      • KCI등재

        정신분열증 치료제에 의한 사람 글루탐산염 탈수소효소 동종효소의 억제효과

        남아름(Nam, A-Reum),김인식(Kim, In-Sik),양승주(Yang, Seung-Ju) 한국산학기술학회 2016 한국산학기술학회논문지 Vol.17 No.1

        글루탐산염(Glutamate)은 척추동물의 중추신경계에서 중요한 흥분성 신경전달물질 중의 하나이다. 글루탐산염의 대 사를 조절하는 사람 글루탐산염 탈수소 효소(hGDH)는 정신분열증(schizophrenia) 환자의 대뇌에서 발현이 증가한다는 연구 들이 있었다. 본 연구에서는 정신분열증과 연관된 항정신성약물인 haloperidol, risperidone, (±)-sulpride, chlopromazine hydrochloride, melperone, (±)butaclamol, domperidone, clozapine에 의한 hGDH의 효소활성변화를 확인하고자 하였다. 우선, 유전자 재조합을 통해 hGDH 동종효소 hGDH1, hGDH<sub>2</sub>를 합성하였다. 합성된 hGDH1과 hGDH<sub>2</sub>에 대한 항정신성약물의 억 제효과를 효소검사법(enzyme assay)을 통해 확인한 결과, haloperidol, (±)-sulpride, melperone, clozapine에 의해 hGDH1과 hGDH<sub>2</sub>의 효소활성이 억제되었다. 또한, 단백질 인산화 효소 측정법(kinase assay)을 하여 haloperidol이 기질인 알파-케토글 루타르산에 대하여는 비경쟁적 저해반응(noncompetitive inhibition)을, NADH에 대하여서는 반경쟁적 저해반응(uncompetitive inhibition)이 나타는 것을 확인하였다. 입체성 다른 자리 작동체(allosteric effector)인 L-leucine이 다른 정신병치료제에서는 hGDH<sub>2</sub>의 억제를 회복시켰지만 오직 haloperidol에서는 효소의 활성이 회복되지 않았다. 따라서 본 연구는 hGDH1과 hGDH<sub>2</sub> 에서 항정신성약물에 의한 효소활성 억제를 비교하여 확인하였으며, 중추신경계에서 haloperidol이 GDH 활성 조절과 함께 글루탐산 농도를 조절할 수 있다는 가능성을 제시한다. Glutamate is one of the major excitatory neurotransmitters in the central nervous system of vertebrates. Human GDH (hGDH) is the enzyme that regulates the glutamate metabolism and its expression is higher in the brains of schizophrenia patients than in normal subjects. This study examined the changes in the hGDH enzymatic activity caused by antipsychotic drugs (haloperidol, risperidone, (±)-sulpride, chlopromazine hydrochloride, melperone, (±)butaclamol, domperidone, clozapine) related to schizophrenia. First of all, hGDH isozymes (hGDH1, hGDH<sub>2</sub>) were synthesized by genetic recombination. As a result of the enzyme assay, haloperidol, (±)-sulpride, melperone and clozapine had an inhibitory effect on the hGDH isozymes. In addition, haloperidol showed a non-competitive inhibition against the substrate, 2-oxoglutarate. In contrast, it showed an uncompetitive inhibition against another substrate, NADH. The inhibitory effect of haloperidol on hGDH<sub>2</sub> was abolished by the presence of L-leucine, an allosteric effector of hGDH, but by not other antipsychotic drugs. These results revealed the inhibition of enzyme activity by psychotropic drugs in hGDH isoenzymes (hGDH1 and hGDH<sub>2</sub>) and the possibility that haloperidol may be used to regulate the GDH activity and glutamate concentration in the central nervous system.

      • KCI등재

        면지 탐색활동을 포함한 그림책 읽기가 유아의 이야기 이해력과 읽기 태도에 미치는 영향

        남아름 ( Nam A-reum ),이시자 ( Lee Si-ja ) 한국어린이문학교육학회 2018 어린이문학교육연구 Vol.19 No.3

        그림책의 면지는 본문과 표지를 연결시켜 책을 구성하는 하나의 장치였으나, 현대의 그림책 작가들은 면지에서 부터 이야기를 시작하거나 새로운 결말을 암시하는 등 의미 있는 지면으로 면지를 활용하고 있다. 이에 본 연구는 그림책 면지 탐색활동이 유아의 이야기 이해력과 읽기 태도에 미치는 영향을 확인하고자 수행되었다. 연구대상은 인천 시에 소재한 H어린이집과 S어린이집 만 5세 유아 각 15명씩으로, 총 24회의 실험이 진행되었다. 구체적으로 실험집단은 앞과 뒷면지가 서로 다른 그림책 24권을 활용하여 예측하기, 비교하기, 경험에 비추어 이야기하기, 상상하기의 면지 탐색활동을 포함한 그림책 읽기를 경험하였으며, 한편 비교집단은 면지 탐색활동 없이 그림책 읽기만을 진행하였다. 그 결과, 실험집단 유아들의 이야기 이해력과 읽기 태도 모두 비교집단에 비해 통계적으로 유의미한 정도로 높게 나타났다. 이는 그림책 읽기에서 면지 탐색활동의 교육적 가치를 확인시켜주는 결과로, 유아교육현장의 교사는 면지 탐색활동의 중요성을 인식하고 보다 효과적인 그림책 읽기를 계획하여야 함을 시사한다. This study investigated the effects of reading picturebooks including the exploration of endpapers on young children’s story comprehension and reading attitude. The study consisted of 15 children from S and H public child care centers located in Incheon, and the experiment was conducted a total of 24 times. Specifically, the children in the experimental group read 24 picturebooks that have different front and back endpapers. They explored these books by guessing, comparing, explaining by relating to their own experiences and imagining, while the control group just read picturebooks without the exploration of the endpapers. The results of the study showed that children’s story comprehension and reading attitude in the experimental group were statistically higher than those of the control group. This finding confirms the educational value of exploring the endpapers while reading picturebooks. It suggests that teachers in the early childhood education field should recognize the importance of exploring endpapers so that picturebooks are read more effectively.

      • Quantification of Antioxidant Phenolic Compounds in a New Chrysanthemum Cultivar by High-Performance Liquid Chromatography with Diode Array Detection and Electrospray Ionization Mass Spectrometry

        Han, Ah-Reum,Kim, Hyo Young,So, Yangkang,Nam, Bomi,Lee, Ik-Soo,Nam, Joo-Won,Jo, Yeong Deuk,Kim, Sang Hoon,Kim, Jin-Baek,Kang, Si-Yong,Jin, Chang Hyun Hindawi 2017 International journal of analytical chemistry Vol.2017 No.-

        <P>The flowers of<I> Chrysanthemum morifolium</I> Ramat. have been used as an herbal tea and in traditional medicine, and the plant has been developed to produce horticultural cultivars of various colors and shapes. In this study, a new chrysanthemum cultivar with dark purple petals (<I>C. morifolium</I> cv. ARTI-Dark Chocolate; ADC) was developed by radiation-induced mutation breeding of its original cultivar with purple striped white petals (<I>C. morifolium</I> cv. Noble Wine, NW). The phenolic profile and antioxidant property of ADC were investigated and compared with NW and the commercially available medicinal herb,<I> C. morifolium</I> with yellow petals (CM), in order to find a scientific support to produce a new source of natural antioxidant. Flavonoid and phenolic acid profiles of the ethanol extracts of the three flowers were analyzed by high-performance liquid chromatography-diode array detector-electrospray ionization mass spectrometry (HPLC-DAD-ESIMS), while antioxidant properties were evaluated using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay. Among the tested flowers, ADC possessed the strongest antioxidant capacity and the highest phenolic contents. Flavonoids (acacetin, apigenin, luteolin, acacetin-7-<I>O</I>-<I>β</I>-glucoside, apigenin-7-<I>O</I>-<I>β</I>-glucoside, luteolin-7-<I>O</I>-<I>β</I>-glucoside, and linarin) and phenolic acids (chlorogenic acid and mixture of 1,4-, 1,5-, and 3,5-dicaffeoylquinic acids) were identified and quantified.</P>

      • KCI등재

        Heterometal-Coordinated Monomeric Concanavalin A at pH 7.5 from Canavalia ensiformis

        ( Nam-jin Chung ),( Yeo Reum Park ),( Dong-heon Lee ),( Sun-young Oh ),( Jung Hee Park ),( Seung Jae Lee ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.12

        The structure of concanavalin A (ConA) has been studied intensively owing to its specific interactions with carbohydrates and its heterometal (Ca<sup>2+</sup> and Mn<sup>2+</sup>) coordination. Most structures from X-ray crystallography have shown ConA as a dimer or tetramer, because the complex formation requires specific crystallization conditions. Here, we reported the monomeric structure of ConA with a resolution of 1.6 A, which revealed that metal coordination could trigger sugar-binding ability. The calcium coordination residue, Asn14, changed the orientation of carbohydrate-binding residues and biophysical details, including structural information, providing valuable clues for the development and application of detection kits using ConA.

      • Cytotoxic Phenylpropanoids from the Rhizomes of Alpinia galanga

        Nam, Joo-Won,Kim, Sun-Jack,Han, Ah-Reum,Lee, Sang-Kook,Seo, Eun-Kyoung 이화여자대학교 약학연구소 2005 藥學硏究論文集 Vol.- No.15

        A bioassay-guided fractionation of the n-hexane and chloroform extracts of the rhizomes of Alpinia galanga led to the isolation of two active compounds, l'S-l-acetoxychavicol acetate (1) and p-coumaryl alcohol τ-O-methyl ehter (2). 1'S'-1-acetoxychavicol acetate (1) exhibited significant cytotoxicity against all human cancer cell lines tested (A549; 8.14, SNU638; 1.27, HCT16; 1.77, HT1080; 1.2, HL60; IC50 2.39 μg/ml), whereas p-coumaryl alcohol τ-O0methyl ether (2) showed selective cytotoxicity against the SNU638 cell (IC_(50) value of 1.62μg/ml).

      • SCISCIESCOPUS

        Diarylheptanoids from the Seeds of <i>Alpinia katsumadai</i> as Heat Shock Factor 1 Inducers

        Nam, Joo-Won,Kang, Ga-Young,Han, Ah-Reum,Lee, Dongho,Lee, Yun-Sil,Seo, Eun-Kyoung American Chemical Society and American Society of 2011 Journal of natural products Vol.74 No.10

        <P>Seven new diarylheptanoids, (−)-(<I>R</I>)-4″-hydroxyyashabushiketol (<B>1</B>), (3<I>S</I>,5<I>S</I>)-alpinikatin (<B>2</B>), katsumain C (<B>3</B>), 7-<I>epi</I>-katsumain C (<B>4</B>), <I>ent</I>-alpinnanin B (<B>5</B>), <I>ent</I>-alpinnanin A (<B>6</B>), and <I>ent</I>-calyxin H (<B>8</B>), were isolated from the EtOAc extract of the seeds of <I>Alpinia katsumadai</I> together with three known compounds, alpinnanin B (<B>7</B>), epicalyxin H (<B>9</B>), and calyxin H (<B>10</B>). Each isomer mixture of <B>3</B> and <B>4</B>, <B>5</B>–<B>7</B>, and <B>8</B>–<B>10</B> was separated successfully by preparative HPLC using a chiral column. The three isomer mixtures (<B>3</B> and <B>4</B>, <B>5</B>–<B>7</B>, <B>8</B>–<B>10</B>) at 1 μM increased expression of heat shock factor 1 (HSF1) with fold increases of 1.438, 1.190, and 1.316, respectively, which was accompanied with increased expression of heat shock protein (HSP) 27 (1.403-, 1.250-, and 1.270-fold, respectively) and HSP70 (1.373-, 1.313-, and 1.229-fold, respectively) without cellular cytotoxicity, suggesting a possible application of these compounds as HSP inducers. Celastrol was used as a positive control of HSP induction, producing fold increases of 1.066 (HSF1), 1.216 (HSP27), and 1.371 (HSP70) at 1 μM. Compounds <B>1</B> and <B>2</B> did not affect the induction of HSF1 protein.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2011/jnprdf.2011.74.issue-10/np200355n/production/images/medium/np-2011-00355n_0002.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np200355n'>ACS Electronic Supporting Info</A></P>

      • SCISCIESCOPUS

        Systematic targeted gene deletion using the gene-synthesis method in fission yeast

        Nam, Miyoung,Lee, Sook-Jeong,Han, Sangjo,Kim, Dongsup,Lee, Minho,Kang, Eun-Jung,Park, Han-Oh,Lee, Ah-Reum,Lee, Sol,Kim, Cheol-Hee,Kim, Dong-Uk,Hoe, Kwang-Lae Elsevier 2014 Journal of microbiological methods Vol.106 No.-

        <P><B>Abstract</B></P> <P>Genome-wide targeted gene deletion, a systematic method to study gene function by replacing target genes with deletion cassettes, using serial-PCR or block-PCR requires elaborate skill. We developed a novel gene-synthesis method to systematically prepare deletion cassettes on a 96-well basis in fission yeast. We designed the 2129-bp deletion cassette as three modules: a central 1397-bp KanMX4 selection marker module and two flanking 366-bp gene-specific artificial linker modules. The central KanMX4 module can be used in multiple deletion cassettes in combination with different sets of flanking modules. The deletion cassettes consisted of 147 oligonucleotides (93 for the central module+25 for each of the flanking modules+4 for the joints) and the oligonucleotides were designed as ~29mers using an in-house program. Oligonucleotides were synthesized on a 96-well basis and ligated into deletion cassettes without gaps by ligase chain reaction, which was followed by two rounds of nested PCR to amplify trace amounts of the ligated cassettes. After the artificial linkers were removed from the deletion cassettes, the cassettes were transformed into wild-type diploid fission yeast strain SP286. We validated the transformed colonies via check PCR and subjected them to tetrad analysis to confirm functional integrity. Using this method, we systematically deleted 563 genes in the fission yeast <I>Schizosaccharomyces pombe</I> with a >90% success rate and a point-mutation rate of ~0.4 mutations per kb. Our method can be used to create systematic gene deletions in a variety of yeasts especially when it included a bar-code system for parallel analyses.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The deletion cassette was designed as three modules consisting of ~29-mer oligos. </LI> <LI> The oligonucleotide set of the KanMX4 module was commonly used. </LI> <LI> Ligation chain reaction was optimized at 58.3°C and 40cycles. </LI> <LI> Nested PCR using artificial linkers yielded sufficient quantity of deletion cassette. </LI> <LI> The gene-synthesis method yielded a success rate of >90% gene deletion. </LI> </UL> </P>

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