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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.

      • SCOPUSKCI등재
      • 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.

      • KCI등재
      • 草創期에 있어서의 韓·美外交關係 : 修交條約 締結을 中心으로

        鄭東貴 慶熙大學校 1982 論文集 Vol.11 No.-

        Today, it is considered that anyone who sincerely aspire to secure the further improvement and expansion of friendship, cooperation and alliance between Korea and the United States of America, is under obligation to study on how Koreans and Americans accepted and understood such diplomatic relationship at each viewpoint and position, and also, on detailed negotiation between two countries, in an objective and realistic manner, through looking into historical facts concerned. It would be really meaningless, without modern significance only to describe already-known facts, such as formal negotiation history or diplomatic policy between the both Governments. So, it is the most important for us to understand the relationship between Korea and the United States on intelligent and emotional experience and it's people's image toward it's counterpart country. Therefore, in this study, I tried to analyze motivation and details on conclusion of Korea-the United States Friendship Treaty, based on the above viewpoints. The matter I found through this study is considered to be so simple, and it is concluded as follows: It is obvious that, as a whole, the Friendship Treaty had a strong, unilateral and unequal coloring, favoring the United States of America. Moreover, this Treaty guarantee that, for the primary object of U.S.A., the responsibility of American crew care in wrecked ship is liable to Korean Government, and also, America will be treated as "The Most Favored Nation", and consular jurisdiction, so-called, extraterritorial jurisdiction shall be given to Americans. We should consider the following characteristics of this Treaty: First, this treaty was Second one concluded with foreign country, which was followed by Kanghwa Treaty between Korea and Japan, and also, it was our first treaty concluded with European country. Second, the Treaty was not outcome concluded by the subject country, Korea's independent, subjective, diplomatic negotiation toward the United States, but by influence of Li Hung-Chang(1823-1901) of China. In addition, for Korean side, one of the major motivation for conclusion of this Treaty was it's own security preparedness sense originated from it's consciousness of crisis on confrontation between China and Japan in the wake of Japan's advance into Korean Peninsular. Considering the above facts, it can be well said that, on occasion of conclusion of this Treaty, the international political pressure had come even to the Hermit Kingdom of Korea. Anyway, it should be noted that there was a desire and intention in the hearts of mediator, Li, Hung-Chang, King Kojong and a group of Open Door Policy, who had cherished their Power-political ideal aimed at restraining the advance of influence into Korean Peninsular by Japan and Russia bent on their expansionism through arbitration of the United States of America.

      • 韓國語의 意味論的構造에 關한 硏究

        張東煥 成均館大學校 1964 論文集 Vol.9 No.-

        Osgood의 意味微分法에 依해서 韓國語의 意味論的構造의 特徵을 解明하기 爲하여 意味上의 包括性과 使用頻度에 立脚하여 選定된 韓國語의 形容詞反對語로 만들어진 50雙의 7點 形容詞尺度에 依해서 100個의 槪念이 評定되었다. 被驗者로서는 200名의 男女大學生이 使用되었으며 各 被驗者는 100個의 槪念中 5個만을 評定하였다. 50個의 形容詞尺度間에서 얻어진 Pearson의 積率相關係數가 Thurstone의 Centroid Method에 依해서 因子分析되고 抽出된 6個의 centroid factor(全體分散의 65.5%)를 Kaiser의 Varimax criterion에 依해서 回轉하여 그 中 4個因子(全分散의 57.5%)를 解釋하여 다음과 같은 結論을 얻었다. 1. 韓國語의 意味空間은 그 大部分(57.5%)이 評價(30.2%), 力能(13.4%), 活動性(7.0%) 精神的一思辨的評價(6.9%)의 넷 因子에 依해서 構成되고 있다. 2. 韓國語의 意味空間은 그 主要 三 因子에 關한 限, 諸外國語의 그것과 類似하다. 3. 韓國語의 意味論的構造의 特徵은 다음과 같다. a. 評價的因子에서는 道德的評價가 優位하게 나타나고 있어 日本語나 西歐語에 比하여 韓國語의 評價는 道德的인 比重을 더욱 많이 차지하고 있다. b. 精神的一思辯的評價 因子는 韓國語의 意味論的構造에 特有한 因子이며 韓國 사람들의 精神的一思辯的價値置重의 思考方式을 表現하고 있는 것으로 생각된다. For the purpose of finding the characteristics of the semantic structure of the Korean language by S-D technique, and of comparing the results with those of foreign languages, 100 concepts were rated through the 50 adjective pairs selected by their frequency of use and their range of meaning. 200 undergraduates, male and female, were the subjects, each of whom rated only five out of the 100 concepts. The intercorrelations between each two of the 50 scales, based upon 1000 observations(5 concepts×200 subjects), were factor analyzed by Thurstone's Centroid method; and by rotating six centroid factors, four interpretable Varimax rotated factors, which accounts for approximately 58% of the variance of judgements, were resulted and the following conclusions were obtained: 1. The four factors obtained are as follow: Factor Ⅰ,Evaluative, Factor Ⅱ, Potency, Factor Ⅲ, Speculative, and Factor Ⅳ, Activity. 2. So far as the three factors, Evaluative, Potency, Activity, are concerned. the semantic structure of the Korean language is similar to that of foreign languages. 3. The characteristics of the Korean language different from those of the other languages seem to be: a) Moral evaluation is dominant in the Evaluative factor of Korean language, far more than, for example, in the Japanese Moral-correctness Factor appeared in the study of Sagara and others. b) The third Factor, what I call the Speculative, is a factor peculiar to Korean language, and it seems to represent the characteristic of the Korean culture.

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