• 제목/요약/키워드: Repeat Response

검색결과 108건 처리시간 0.023초

Characterization of Mutations in AlHK1 Gene from Alternaria longipes: Implication of Limited Function of Two-Component Histidine Kinase on Conferring Dicarboximide Resistance

  • Luo, Yiyong;Yang, Jinkui;Zhu, Mingliang;Yan, Jinping;Mo, Minghe;Zhang, Keqin
    • Journal of Microbiology and Biotechnology
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    • 제18권1호
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    • pp.15-22
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    • 2008
  • Four series (S, M, R, and W) of Alternaria longipes isolates were obtained based on consecutive selection with Dimethachlon (Dim) and ultraviolet irradiation. These isolates were then characterized according to their tolerance to Dim, sensitivity to osmotic stress, and phenotypic properties. All the selected Dim-resistant isolates showed a higher osmosensitivity than the parental strains, and the last generation was more resistant than the first generation in the M, R, and W series. In addition, the changes in the Dim resistance and osmotic sensitivity were not found to be directly correlated, and no distinct morphologic characteristics were found among the resistant and sensitive isolates, with the exception of the resistant isolate K-11. Thus, to investigate the molecular basis of the fungicide resistance, a group III two-component histidine kinase (HK) gene, AlHK1, was cloned from nineteen A. longipes isolates. AlHK1p was found to be comprised of a six 92-amino-acid repeat domain (AARD), HK domain, and response regulator domain, similar to the Os-1p from Neurospora crassa. A comparison of the nucleotide sequences of the AlHK1 gene from the Dim-sensitive and -resistant isolates revealed that all the resistant isolates contained a single-point mutation in the AARD of AlHK1p, with the exception of isolate K-11, where the AlHK1p contained a deletion of 107 amino acids. Moreover, the AlHK1p mutations in the isolates of each respective series involved the same amino acid substitution at the same site, although the resistance levels differed significantly in each series. Therefore, these findings suggested that a mutation in the AARD of AlHK1p was not the sole factor responsible for A. longipes resistance to dicarboximide fungicides.

LC15-0133, DPP IV 저해제: 여러 동물 모델에서의 효능 (LC15-0133, a DPP IV Inhibitor: Efficacy in Various Animal Models)

  • 임현주
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2008년도 Proceedings of the Convention
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    • pp.5-20
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    • 2008
  • GLP 1 기반의 약(GLP-1 유도체와 DPP IV 저해제)과 인크레틴 유사체는 최근 가장 각광을 받는 2당뇨 치료제 계열 중 하나이다. GLP-1은 위장에서 분비되는 핍타이드 인크레틴 호르몬으로서 췌장으로부터의 당-의존적 인슐린 분비를 증진하고, 위장통과를 지연시키며, 췌장 베타세포의 증식을 촉진한다. DPP IV 저해제는 GLP-1 불활성화시키는 DPP IV 효소의 활성을 저해함으로써 인크레틴처럼 작용한다. LC15-0133은 경쟁적, 가역적 DPP IV 저해제 ($IC_{50}$ = 24 nM, Ki=0.247 nM)이며, DPP II, DPP 8, 엘라스타제, 트릴신, 유로키나제에 비해 DPPIV 에 대한 선택적 억제 효능이 우수하다. LC15-0133 랫과 개에서 긴 반감기와, 우수한 경구흡수율을 보였다. LC15-0133 랫과 개에서 각각 0.1 mg/kg 0.02 mg/kg 용량으로 경구투여하고 24시간이 지난 후에도 50%이상의 혈장 DPP IV 활성 억제효능을 유지하였다. C57BL/6 마우스에서 LC15-013301 경구당부하에 의한 혈당증가를 억제하는 최소유효용량은 0.01 mg/kg, 당에 의한 GLP-1 분비를 증가시키는 최소유효용량은 0.1 mg/kg 이다. Zucker 당뇨 랫에서 LC15-01331의 1개월간의 경구반복투여는 당뇨병으로의 진행을 지연시키고, 혈중 HbA1c 감소시켰다. 결론적으로, LC15-0133은 신규의 강력하고, 선택적인 경구 DPP IV 저해제이며, 여러가지 동물모델에서 탁월한 혈당강하효능을 보였다.

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소매 업태에 따른 판촉활동에 관한 이론적 연구 (A Theoretical Study of Promotion Activities by Types of Retailing)

  • 박진호;이수동
    • 서비스연구
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    • 제7권4호
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    • pp.15-38
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    • 2017
  • 본 연구에서는 상표전환과 반복구매의 소비 형태를 보이는 소비자를 대상으로 그들의 상표전환과 반복구매의 결정 요인은 무엇인지 알아보고자 하며 그러한 상표전환의 과정과 반복구매에서 기업의 촉진활동으로 대표되는 마케팅 반응변수별 차이를 분석하여 그 결과를 마케팅에 적용시키기 위한 시사점을 제공하고자 한다. 이는 유통업계간 과다경쟁과 외형을 중시한 판매경쟁의 결과로 밀어내기식의 마케팅을 전개하고 있는 기업에게 소비자를 개개인의 실체로 인식시켜 이에 맞는 효율적인 촉진활동을 제시함으로써 자사상표에 대한 상표 충성도를 높여 지속적인 반복구매를 하게하고 경쟁상표 소비자의 상표전환을 유도하는데 도움을 주고자 한다. 본 연구 결과를 살펴보면 다음과 같다. 첫 번째 이벤트와 가격할인과 샘플이나 견본상표 혹은 로고(logo) 등이 새겨진 것을 일컫는 제품 프리미엄 등을 선호하는 고객들은 반복구매를 하는 특징이 있다. 두 번째 서비스 혜택과 포인트 형 판촉 그리고 비용절감 만족도가 상표전환에는 아무런 영향을 미치지 못했으며 쿠폰 형 판촉을 선호하는 사람들만이 상표전환을 하는 것으로 나타났다. 세 번째 반복구매와 쿠폰 형 판촉 사이에서는 소매 업태가 긍정적인 조절효과를 보이고 있으며 상표전환과 서비스혜택 사이에서도 소매 업태가 긍정적인 조절효과를 보이고 있는 것을 알 수 있었다.

다발근육염과 피부근육염에서 관찰된 중첩증후군 (Overlap Syndromes in Polymyositis and Dermatomyositis)

  • 박경석;김남희;홍윤호;성정준;남현우;박성호;이광우
    • Annals of Clinical Neurophysiology
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    • 제9권1호
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    • pp.11-15
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    • 2007
  • Background: The term "overlap syndromes" designates a group of diseases in which polymyositis (PM) or dermatomyositis (DM) is associated with some other disorders of connective tissues. The aim of this study was to delineate the clinical features, laboratory findings, and outcome of treatment of "overlap syndromes" Methods: We analyzed the medical records of 16 patients (PM in 10, DM in 6) with well documented "overlap syndromes" between 1997 and 2004. The diagnosis was made when the criteria for two different disorders were fulfilled. Results: All patients were female. Age of onset ranged from 14 to 52 years (mean 29.8 years) with peak incidence in the third and fourth decades. Systemic lupus erythematosus (SLE) was associated in 10, systemic sclerosis in 7, and rheumatoid arthritis in 3 patients. Four of the patients had two different connective tissue diseases simultaneously. The characteristic clinical features were muscle weakness, arthralgia, Raynaud's phenomenon, and myalgia. In laboratory tests, creatine kinase (CK), lactic dehydrogenase (LDH), and transaminases were usually abnormal. Positive antinuclear antibody (ANA), rheumatoid factor (RF), and cryoglobulin were found in 100%, 69%, and 67% of the patients, respectively. Needle electromyography (EMG) showed abnormal findings compatible with myopathy in 15 patients. The pathology of muscle biopsy from 14 patients revealed findings compatible with inflammatory myopathy. Glucocorticoids were administered to 15 patients. The muscle strength improved in all the treated patients, which was well correlated with repeat CK level and EMG findings. Conclusions: The presence of autoantibodies such as ANA, RF, and cryoglobulin in patients with PM or DM highly suggests the possibility of an overlap syndromes. These syndromes reveal a strong female predominance. The myositis associated with them usually shows a good response to glucocorticoids treatment.

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Locating QTLs controlling overwintering seedling rate in perennial glutinous rice 89-1 (Oryza sativa L.)

  • Deng, Xiaoshu;Gan, Lu;Liu, Yan;Luo, Ancai;Jin, Liang;Chen, Jiao;Tang, Ruyu;Lei, Lixia;Tang, Jianghong;Zhang, Jiani;Zhao, Zhengwu
    • Genes and Genomics
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    • 제40권12호
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    • pp.1351-1361
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    • 2018
  • A new cold tolerant germplasm resource named glutinous rice 89-1 (Gr89-1, Oryza sativa L.) can overwinter using axillary buds, with these buds being ratooned the following year. The overwintering seedling rate (OSR) is an important factor for evaluating cold tolerance. Many quantitative trait loci (QTLs) controlling cold tolerance at different growth stages in rice have been identified, with some of these QTLs being successfully cloned. However, no QTLs conferring to the OSR trait have been located in the perennial O. sativa L. To identify QTLs associated with OSR and to evaluate cold tolerance. 286 $F_{12}$ recombinant inbred lines (RILs) derived from a cross between the cold tolerant variety Gr89-1 and cold sensitive variety Shuhui527 (SH527) were used. A total of 198 polymorphic simple sequence repeat (SSR) markers that were distributed uniformly on 12 chromosomes were used to construct the linkage map. The gene ontology (GO) annotation of the major QTL was performed through the rice genome annotation project system. Three main-effect QTLs (qOSR2, qOSR3, and qOSR8) were detected and mapped on chromosomes 2, 3, and 8, respectively. These QTLs were located in the interval of RM14208 (35,160,202 base pairs (bp))-RM208 (35,520,147 bp), RM218 (8,375,236 bp)-RM232 (9,755,778 bp), and RM5891 (24,626,930 bp)-RM23608 (25,355,519 bp), and explained 19.6%, 9.3%, and 11.8% of the phenotypic variations, respectively. The qOSR2 QTL displayed the largest effect, with a logarithm of odds score (LOD) of 5.5. A total of 47 candidate genes on the qOSR2 locus were associated with 219 GO terms. Among these candidate genes, 11 were related to cell membrane, 7 were associated with cold stress, and 3 were involved in response to stress and biotic stimulus. OsPIP1;3 was the only one candidate gene related to stress, biotic stimulus, cold stress, and encoding a cell membrane protein. After QTL mapping, a total of three main-effect QTLs-qOSR2, qOSR3, and qOSR8-were detected on chromosomes 2, 3, and 8, respectively. Among these, qOSR2 explained the highest phenotypic variance. All the QTLs elite traits come from the cold resistance parent Gr89-1. OsPIP1;3 might be a candidate gene of qOSR2.

자궁내막 염증에 대한 지엽적 에스트로겐 및 프로게스테론 매개 수용체의 역할 (Roles of Local Estrogen and Progesterone Mediated Receptors in the Regulation of Endometrial Inflammation)

  • 민계식
    • 생명과학회지
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    • 제33권1호
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    • pp.102-113
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    • 2023
  • 본 총설에서는 지난 수년 동안 자궁내막 염증 관련 새롭게 밝혀진 에스트로겐과 프로게스테론 수용체의 기능 중 지엽적 에스트로겐의 합성, 특이적 에스트로겐 수용체의 조절, 프로게스테론 저항성 그리고 스테로이드 호르몬의 작용에 의한 자궁내막 조직세포의 염증반응, 분화 및 생존에 대한 세포 및 분자적 조절기전들을 고찰한다. 자궁내막 조직 기질세포의 비정상적인 후성유전체적 변화는 자궁내막증의 발병과 진행에 중요한 요인으로 작용한다. 특히, 에스트로겐 수용체 유전자들의 차별적 메틸화는 기질세포내 ERα로부터 ERβ로의 발현 우세도 전환을 유도하여, ERβ-매개 염증반응, 프로게스테론 저항성 및 레티노이드 합성장애 등의 비정상적인 에스트로겐 반응을 초래한다. 이 기질세포는 또한 PGE2 및 SF-1 매개에 의한 스테로이드 합성효소의 발현유도를 통하여 지엽적 에스트로겐의 생성을 촉진하며, 증가된 에스트라디올은 다시 ERβ에 피드백으로 작용하여 COX-2 촉진을 통한 염증반응의 악순환을 야기한다. 높은 ERβ의 발현은 중간엽 줄기세포의 염색질 구조변화릉 야기하여 프로게스테론 저항성을 획득하고, 이는 반복적 생리에 따른 지속적 노출로 자궁내막 조직의 염증을 형성하며, 이후에는 ERβ-매개 에스트로겐과 TNF-α 및 TGF-β1을 포함한 염증 유발 인자들이 작용하여 염증 조직세포의 부착, 혈관생성 및 생존과 기질세포의 분화조절장애를 유도한다. 따라서, 생리주기의 역동적인 호르몬 변화와 이에 따르는 자궁내막 조직의 핵수용체 신호전달 조절기전에 대한 구체적인 이해는 정상적인 생식기능을 유지하면서 자궁내막증과 같은 비정상적 염증질환을 치료하기 위한 새로운 안목을 제공할 수 있을 것으로 기대된다.

Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation

  • TaeKyung Nam;Wonku Kang;Sangtaek Oh
    • Journal of Microbiology and Biotechnology
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    • 제33권9호
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    • pp.1206-1212
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    • 2023
  • The Wnt/β-catenin pathway plays essential roles in regulating various cellular behaviors, including proliferation, survival, and differentiation [1-3]. The intracellular β-catenin level, which is regulated by a proteasomal degradation pathway, is critical to Wnt/β-catenin pathway control [4]. Normally, casein kinase 1 (CK1) and glycogen synthase kinase-3β (GSK-3β), which form a complex with the scaffolding protein Axin and the tumor suppressor protein adenomatous polyposis coli (APC), phosphorylate β-catenin at Ser45, Thr41, Ser37, and Ser33 [5, 6]. Phosphorylated β-catenin is ubiquitinated by the β-transducin repeat-containing protein (β-TrCP), an F-box E3 ubiquitin ligase complex, and ubiquitinated β-catenin is degraded via a proteasome pathway [7, 8]. Colorectal cancer is a significant cause of cancer-related deaths worldwide. Abnormal up-regulation of the Wnt/β-catenin pathway is a major pathological event in intestinal epithelial cells during human colorectal cancer oncogenesis [9]. Genetic mutations in the APC gene are observed in familial adenomatous polyposis coli (FAP) and sporadic colorectal cancers [10]. In addition, mutations in the N-terminal phosphorylation motif of the β-catenin gene were found in patients with colorectal cancer [11]. These mutations cause β-catenin to accumulate in the nucleus, where it forms complexes with transcription factors of the T-cell factor/lymphocyte enhancer factor (TCF/LEF) family to stimulate the expression of β-catenin responsive genes, such as c-Myc and cyclin D1, which leads to colorectal tumorigenesis [12-14]. Therefore, downregulating β-catenin response transcription (CRT) is a potential strategy for preventing and treating colorectal cancer. Plant cytokinins are N6-substituted purine derivatives; they promote cell division in plants and regulate developmental pathways. Natural cytokinins are classified as isoprenoid (isopentenyladenine, zeatin, and dihydrozeatin), aromatic (benzyladenine, topolin, and methoxytopolin), or furfural (kinetin and kinetin riboside), depending on their structure [15, 16]. Kinetin riboside was identified in coconut water and is a naturally produced cytokinin that induces apoptosis and exhibits antiproliferative activity in several human cancer cell lines [17]. However, little attention has been paid to kinetin riboside's mode of action. In this study, we show that kinetin riboside exerts its cytotoxic activity against colon cancer cells by suppressing the Wnt/β-catenin pathway and promoting intracellular β-catenin degradation.

인터넷 커뮤니티에서 사용자 참여가 밀착도와 지속적 이용의도에 미치는 영향 (A Study on the Effects of User Participation on Stickiness and Continued Use on Internet Community)

  • 고미현;권순동
    • Asia pacific journal of information systems
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    • 제18권2호
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    • pp.41-72
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    • 2008
  • The purpose of this study is the investigation of the effects of user participation, network effect, social influence, and usefulness on stickiness and continued use on Internet communities. In this research, stickiness refers to repeat visit and visit duration to an Internet community. Continued use means the willingness to continue to use an Internet community in the future. Internet community-based companies can earn money through selling the digital contents such as game, music, and avatar, advertizing on internet site, or offering an affiliate marketing. For such money making, stickiness and continued use of Internet users is much more important than the number of Internet users. We tried to answer following three questions. Fist, what is the effects of user participation on stickiness and continued use on Internet communities? Second, by what is user participation formed? Third, are network effect, social influence, and usefulness that was significant at prior research about technology acceptance model(TAM) still significant on internet communities? In this study, user participation, network effect, social influence, and usefulness are independent variables, stickiness is mediating variable, and continued use is dependent variable. Among independent variables, we are focused on user participation. User participation means that Internet user participates in the development of Internet community site (called mini-hompy or blog in Korea). User participation was studied from 1970 to 1997 at the research area of information system. But since 1997 when Internet started to spread to the public, user participation has hardly been studied. Given the importance of user participation at the success of Internet-based companies, it is very meaningful to study the research topic of user participation. To test the proposed model, we used a data set generated from the survey. The survey instrument was designed on the basis of a comprehensive literature review and interviews of experts, and was refined through several rounds of pretests, revisions, and pilot tests. The respondents of survey were the undergraduates and the graduate students who mainly used Internet communities. Data analysis was conducted using 217 respondents(response rate, 97.7 percent). We used structural equation modeling(SEM) implemented in partial least square(PLS). We chose PLS for two reason. First, our model has formative constructs. PLS uses components-based algorithm and can estimated formative constructs. Second, PLS is more appropriate when the research model is in an early stage of development. A review of the literature suggests that empirical tests of user participation is still sparse. The test of model was executed in the order of three research questions. First user participation had the direct effects on stickiness(${\beta}$=0.150, p<0.01) and continued use (${\beta}$=0.119, p<0.05). And user participation, as a partial mediation model, had a indirect effect on continued use mediated through stickiness (${\beta}$=0.007, p<0.05). Second, optional participation and prosuming participation significantly formed user participation. Optional participation, with a path magnitude as high as 0.986 (p<0.001), is a key determinant for the strength of user participation. Third, Network effect (${\beta}$=0.236, p<0.001). social influence (${\beta}$=0.135, p<0.05), and usefulness (${\beta}$=0.343, p<0.001) had directly significant impacts on stickiness. But network effect and social influence, as a full mediation model, had both indirectly significant impacts on continued use mediated through stickiness (${\beta}$=0.11, p<0.001, and ${\beta}$=0.063, p<0.05, respectively). Compared with this result, usefulness, as a partial mediation model, had a direct impact on continued use and a indirect impact on continued use mediated through stickiness. This study has three contributions. First this is the first empirical study showing that user participation is the significant driver of continued use. The researchers of information system have hardly studies user participation since late 1990s. And the researchers of marketing have studied a few lately. Second, this study enhanced the understanding of user participation. Up to recently, user participation has been studied from the bipolar viewpoint of participation v.s non-participation. Also, even the study on participation has been studied from the point of limited optional participation. But, this study proved the existence of prosuming participation to design and produce products or services, besides optional participation. And this study empirically proved that optional participation and prosuming participation were the key determinant for user participation. Third, our study compliments traditional studies of TAM. According prior literature about of TAM, the constructs of network effect, social influence, and usefulness had effects on the technology adoption. This study proved that these constructs still are significant on Internet communities.