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        Divergent reprogramming routes lead to alternative stem-cell states

        Tonge, Peter D.,Corso, Andrew J.,Monetti, Claudio,Hussein, Samer M. I.,Puri, Mira C.,Michael, Iacovos P.,Li, Mira,Lee, Dong-Sung,Mar, Jessica C.,Cloonan, Nicole,Wood, David L.,Gauthier, Maely E.,Korn, Nature Publishing Group, a division of Macmillan P 2014 Nature Vol.516 No.7530

        Pluripotency is defined by the ability of a cell to differentiate to the derivatives of all the three embryonic germ layers: ectoderm, mesoderm and endoderm. Pluripotent cells can be captured via the archetypal derivation of embryonic stem cells or via somatic cell reprogramming. Somatic cells are induced to acquire a pluripotent stem cell (iPSC) state through the forced expression of key transcription factors, and in the mouse these cells can fulfil the strictest of all developmental assays for pluripotent cells by generating completely iPSC-derived embryos and mice. However, it is not known whether there are additional classes of pluripotent cells, or what the spectrum of reprogrammed phenotypes encompasses. Here we explore alternative outcomes of somatic reprogramming by fully characterizing reprogrammed cells independent of preconceived definitions of iPSC states. We demonstrate that by maintaining elevated reprogramming factor expression levels, mouse embryonic fibroblasts go through unique epigenetic modifications to arrive at a stable, Nanog-positive, alternative pluripotent state. In doing so, we prove that the pluripotent spectrum can encompass multiple, unique cell states.

      • SCOPUSSCIEKCI등재

        Neuroprotective Effects of Quetiapine on Neuronal Apoptosis Following Experimental Transient Focal Cerebral Ischemia in Rats

        Yilmaz, Muhammet Bahadir,Tonge, Mehmet,Emmez, Hakan,Kaymaz, Figen,Kaymaz, Memduh The Korean Neurosurgical Society 2013 Journal of Korean neurosurgical society Vol.54 No.1

        Objective : This study was undertaken in the belief that the atypical antipsychotic drug quetiapine could prevent apoptosis in the penumbra region following ischemia, taking into account findings that show 5-hydroxytryptamine-2 receptor blockers can prevent apoptosis. Methods : We created 5 groups, each containing 6 animals. Nothing was done on the K-I group used for comparisons with the other groups to make sure adequate ischemia had been achieved. The K-II group was sacrificed on the 1st day after transient focal cerebral ischemia and the K-III group on the 3rd day. The D-I group was administered quetiapine following ischemia and sacrificed on the 1st day while the D-II group was administered quetiapine every day following the ischemia and sacrificed on the 3rd day. The samples were stained with the immunochemical TUNEL method and the number of apoptotic cells were counted. Results : There was a significant difference between the first and third day control groups (K-II/K-III : p=0.004) and this indicates that apoptotic cell death increases with time. This increase was not encountered in the drug groups (D-I/D-II : p=1.00). Statistical analysis of immunohistochemical data revealed that quetiapine decreased the apoptotic cell death that normally increased with time. Conclusion : Quetiapine is already in clinical use and is a safe drug, in contrast to many substances that are used to prevent ischemia and are not normally used clinically. Our results and the literature data indicate that quetiapine could help both as a neuronal protector and to resolve neuropsychiatric problems caused by the ischemia in cerebral ischemia cases.

      • SCISCIESCOPUS

        Genome-wide characterization of the routes to pluripotency

        Hussein, Samer M. I.,Puri, Mira C.,Tonge, Peter D.,Benevento, Marco,Corso, Andrew J.,Clancy, Jennifer L.,Mosbergen, Rowland,Li, Mira,Lee, Dong-Sung,Cloonan, Nicole,Wood, David L. A.,Munoz, Javier,Midd Nature Publishing Group, a division of Macmillan P 2014 Nature Vol.516 No.7530

        Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.

      • KCI등재

        Cytological, genetic, and proteomic analysis of a sesame (Sesamum indicum L.) mutant Siyl‑1 with yellow–green leaf color

        Tong‑Mei Gao,Shuang‑Ling Wei,Jing Chen,Yin Wu,Feng Li,Li‑Bin Wei,Chun Li,Yan‑Juan Zeng,Yuan Tian,Dong‑Yong Wang,Hai‑Yang Zhang 한국유전학회 2020 Genes & Genomics Vol.42 No.1

        Background Both photosynthetic pigments and chloroplasts in plant leaf cells play an important role in deciding on the photosynthetic capacity and efficiency in plants. Systematical investigating the regulatory mechanism of chloroplast development and chlorophyll (Chl) content variation is necessary for clarifying the photosynthesis mechanism for crops. Objective This study aims to explore the critical regulatory mechanism of leaf color mutation in a yellow–green leaf sesame mutant Siyl-1. Methods We performed the genetic analysis of the yellow-green leaf color mutation using the F2 population of the mutant Siyl-1. We compared the morphological structure of the chloroplasts, chlorophyll content of the three genotypes of the mutant F2 progeny. We performed the two-dimensional gel electrophoresis (2-DE) and compared the protein expression variation between the mutant progeny and the wild type. Results Genetic analysis indicated that there were 3 phenotypes of the F2 population of the mutant Siyl-1, i.e., YY type with light-yellow leaf color (lethal); Yy type with yellow-green leaf color, and yy type with normal green leaf color. The yellowgreen mutation was controlled by an incompletely dominant nuclear gene, Siyl-1. Compared with the wild genotype, the chloroplast number and the morphological structure in YY and Yy mutant lines varied evidently. The chlorophyll content also significantly decreased (P < 0.05). The 2-DE comparison showed that there were 98 differentially expressed proteins (DEPs) among YY, Yy, and yy lines. All the 98 DEPs were classified into 5 functional groups. Of which 82.7% DEPs proteins belonged to the photosynthesis and energy metabolism group. Conclusion The results revealed the genetic character of yellow-green leaf color mutant Siyl-1. 98 DEPs were found in YY and Yy mutant compared with the wild genotype. The regulation pathway related with the yellow leaf trait mutation in sesame was analyzed for the first time. The findings supplied the basic theoretical and gene basis for leaf color and chloroplast development mechanism in sesame.

      • SCOPUSKCI등재
      • KCI등재
      • 美國地方自治政府의 環境變化와 그 組織構造의 變化에 관한 考察

        金東勳 충남대학교 경상대학부설 경영경제연구소 1981 경영논집 Vol.3 No.1

        Ⅰ. Environmental Changes and Reorganization Needs The urban, particularly metropolitan counties in the United States are faced with an increasingly need to expand their services, but they suffer from the archaic administrative organizations and skills, lack of central locus of power, an excess of elective offices and the practice of various spoils. The metropolitan governments are particularly faced with various socio-economic and political problems and they suffer from conflict of many interests. Increasingly, a need is felt in the United States for a strong executive in the administration of the urban, particularly metropolitan counties. The citizens refuse to pay higher taxes, but they demand better services and an efficient administration. The traditional fragmentation of power in the government, the profusion of elective local officials and the lack of capable administrative personnel have been responsible for a weak government at the local level in the United States and a waste of financial and other resources. Ⅱ. Direction of Reorganization 1. Counties Various reorganization efforts have been made. Many counties now have a charter. Some urban counties have reformed their traditional administrative structures and introduced modern administrative skills. Some urban counties have adopted a manager plan or a county-executive plan with a chief administrattive officer (CAO). 2. Townships The development in communication and transportation in the United States has transformed the concept of time and space and the traditional township government has lost its usefulness. Its unit of government is too small to be effective and economical. Some urban townships are maintained, but increasingly political scientists argue for the need to abolish their township system. 3. Municipalities The structure of municipal government in the United States is affected by its environments such as geographical size, population and its growth rate, existence of political conficts and party competition and social class composition. a). The commission form of municipal government has been losing its support and viability due to its inherent adminstrative weaknesses. b). The mayor-council form is increasingly used. It is believed to provide a stronger political leadership need to administer a large metropolitan area. A strong mayor system has been replacing a weak mayor system. Particularly favored is a strong mayor-administrator form. c). The council-manager form is used in the mid-sized cities in the United States. This type of city is characteristically inhabited by the white people of relatively good education high income and white-collar job. The commission form and the mayor-council form of government have declined in number in this type of city. d). The small cities do not possess the human and other resources to appoint a capable, professionally oriented administrator. As a result, their most prevalent form of government is still the mayor-council system.

      • Fe 중에 Nd확산에 관한 연구(R-D반응의 기초연구)

        조통래,송창빈,김대수 忠南大學校 産業技術硏究所 1992 산업기술연구논문집 Vol.7 No.1

        The growth of intermetallic compounds of rare earth-transition metal has been investigated by the reduction process. Nd was diffused into Fe block and made intermetallic compounds, only the Nd₂Fe17 diffusion layer was obtained for the Nd-Fe system. It was shown that the growth rate of intermetallic compounes was controlled by diffusion. Apprarent activation energy for the diffusion of Nd was 28.5Kcal/mol through arrhenius plots.

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