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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
      • 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.

      • 우리나라 關稅制度에 관한 硏究 : with refer to Heavy & Chemical Imdustry Development

        朴東浩 서경대학교 1977 論文集 Vol.4-5 No.-

        1. In relation to the policy of industrial structure, the present tariff system raises some problems as to tariff exemption system, elastic tariff system, bonded system and tariff rate system. 2. Tariff exemption system concerns tariff exemptions, tariff exemption by agreement as well as tariff exemptions under customs law and other ordinances. Tariff exemption under customs law amounts to 11 items, and under other ordinances amounts to 4 items and that by agreement amounts to 5. And a sum total of the tariff exemption of the latter two occupies no more than 10 per cent of the sum total of the whole tariff exemptions. The present tariff exemption system raises such problems as (1) a diversity of tariff exemption system, (2) decrease in tariff revenues owing to an increase in the amount of tariff exemption, (3) uniform exemption system for key industry and the period of tariff exemption and (4) adjustment as to the fixed drawback rate. (1) In the light of a diversity of tariff exemption system, the effects of exemption can be unreasonably overlapped. Therefore, a single unified system is required. (2) The amount of tariff exemptions exceeds the collected amount of tariffs with its revenue tending relatively to decrease. Owing to the encouragement of import for tax-exempt items and the ever-widening gap between the nominal tariff rate and effective tariff rate, a special meausre is to be taken to reduce the number of tariff exemption items except for the heavy & chemical industry and daily necessities. By improving trade balance and protecting domestic industry and narrowing the gap between nominal tariff rate and effective rate, we must see that resources be reasonalby distributed. (3) Tariff exemption for key industry ranges widely in its scope. Except for petrochemical refineries and resident-firms in the export industry areas, at present 80 per cent tariff exemptions are equally applied to other industries without a consideration given to the priority of growth and the difference of basic of basic tariff rates. Since there is no time-limit to tariff exemption, it is advisable to reduce the scope of tariff exemption and to introduce installment-pay system of tariff. And the tariff rates must be adjusted differently according to the strategic importance of heavy chemical industry. The tariff rates must also be adjusted differently an consideration of each period and stage of the growth of industry. (4) Since the amount of drawback tariff rate exercises a considerable influence on the technological development of each industry, a serious consideration is required as to the exact amount of raw materials. 3. Elastic tariff system comprises anti-dumping, retaliatory tariff, emergency tariff, countervailing-tariff, benificial tariff, tariff quota system and limited mandatory tariff system. At present, 400-odd items are subject to elastic tariff rate. Elastic tariff system is required to cope with such problems as: (1) the scope of the system becomes gretaer and more fixed each year; (2) it is difficult to apply equable elastic rate to each different item; (3) a necessity arises regarding domestic elastic tariff and import-control policy. (1) Elastic tariff serves as a defensive measure rather·than offensive one in the international trade. As it is dynamically subject to the drastic changes of economic situations at home or abroad, the tariff rates are determined inside the framework of law. Therefore, it s proper that the rate should return to normal when the particular situations cease to exist. When a structural change of industry necessitates the application of elastic rate, the tariff rate must be reformed rather than revised to well cope with the situation. (2) In deciding any items to be subject to elastic tariff rate, the following factors are to be considered as a frame of reference such as domestic demand, domestic production qountity, domestic production cost and export price of major rival nations. Nevetheless, in order to secure objectivity on the application of elastic rate, the tariff standard must be decided by mathematical and scientific methods. (3) Occasional disharmony between the direct policy of import restrictions and indirect policy of tariff may produce in efficiency or a decrease in the effect of the policy. Coordination between the two policies are required. 4. Bonded system includes bonded area system and bonded transportion system. Bonded area system concerns designated bonded areas and licensed honded area. In the licensed bonded area are included bonded warehouse, bonded shed, bonded manufacturing warehouse, bonded exhibition ground and bonded construction ground. Bonded manufacturing warehouse, among others, occupies an important position in the light of industrial policy. Bonded manufacturing warehouse includes export bonded manufacturing warehouse, bonded manufacturing warehouse for domestic demand and licensed bonded manufacturing warehouse. Export free trade areas and export industrial areas can also claim their importance. At present, export honded manufacturing warehouse amounts to 330 in number, bonded manufacturing warehouse for domestic demand 28, and resident-firms in the export free trade areas and export industry areas amount to 491 in number. The present bonded system has the following problems to cope with: (1) There is no restirction placed on the conditions to establish bonded manufacturing warehouse; (2) Bonded manufacturing warehouse for domestic demand not only widens the gap between the nomincal tariff rates and effective tariff rates but also create an issue overlapping as to the management of elastic tariff and bonded manufacturing warehouse for domestic demand. (1) With a view to enhancing the processing industry alone, it deems unnecessary in principle to place any restriction on the establishment of bonded warehouse. But from the standpoint of industrial policy, it is necessary, as is the case with other countries including Japan, to restrict the establishment of what may exercise a damaging influences on domestic industry or aim to take advantage of a low tariff rates. (2) Bonded manufacturing warehouse for domestic demand system is convenient regarding assemly imports and customs clearance. But it is hardly conducive to industrial policy as a whole. Therefore, it is recommended that the policy be oriented toward abolishing the system. And then tariff rates for partial goods and finished goods are required to apply to homogeneouse industries. 5. Tariff rate system adopts both the tariff system and compound tariff system. As of June 1, 1975, there are 197 items subjects to GATT conventional tariff rates, 6 items subject to concession on tariff rates among developing countries and other items subject to autonomouse tariff rates. 11 items of those items are subject to provisional tariff, 443 items to elastic tariff and the rest to general rates Also in relation to the bais of tariff, there are 23 items subject to specific tariff, 7 items to alternative tariff and the rest to ad valorem tariff. Under the present tariff rate system, a majority of export-import goods are subject to ad valorem tariff. As a result, the present system tends to weaken the protective function of domestic industry by way of encouraging the importation ofinexpensive foreign commodities with a view to evadingtaxaion. Therefore, it is recommended that the scope of ad valorem tariff be expanded. 6. There are 17 steps in tariff rate system. Financial duties items (5∼20%) occupy 51, 1 percent; protective banned items (50∼80%) 2.8 per cent and the average tariff rates amount to 31, 5 per cent. According to the inter-industrial Relations Table of 1973, the relation between nominal tariff rates and effective tariff rates shows that pig iron amounts to 10 per cent vs. 2, 1 per cent; steel ore, 10∼20 per cent vs. 1, 4 per cent; alloy, 5 per cent vs. 6, 5 per per cent; iron plate, 35∼40 percent vs. 4, 9 per cent; steel bar, 25 per cent vs. 8, 3 per cent, mould steel, 25 per cent vs. 7, 6 per cent; the other iron-steel godds, 25∼35 per cent vs. 5, 2 per cent. Steel pipe, 20∼50 per cent vs. 17, 7 per cent. Plated steel materials, 40 per cent vs. 10,8 per cent; cast-steel, 40 per cent vs. 3, 5 per cent; cast-iron pipe, 40 per cent vs. 1, 4 per cent; wrought steel, 50 per cent vs. 25 percent. Thuse average tariff rate for iron-stell goods stands 27∼30 per cent against 7, 9 per cent, the difference being as much as 19,1∼23,9 per cent. In the case of shipping, the ratio stand 10∼25 per cent against 1 per cent, the differecne being 9∼24 per cent. In machinery, the ratio stand 11,5∼27,5 against 5,6, the difference being 26,3∼36,3 per cent. In electronics goods, the ratio stands 60∼70 per cent against 3,4 per cent, the difference being 56,6∼66,6 per cent. As is clearly shown in the figures above, we can see that from the standpoint of tariff rate structure (1) effective tariff is lower in heavy & chemical industry than in light industry; (2) tariff is imposed more heavily on the finished goods than on parts in the case of machinery; (3) unlike nominal tariff rate applicable to each production stage, effective taniff rate does not show the same tendency as above and (4) the difference between nominal tariff rate and effective tariff rate is much to big. First, from the standpoint of tariff protection, the difference between light industry and heavy & chemical industry will create added value ratio on the light industry, thus promting the preferential ldevelopment of light industry. Therefore it is recommended that effective teriff rate be lowered in ight industry and raised in heavy & chemical industry. Second, advantag given to finished goods over parts may result in encouraging the mere production of intermediate goods. Therefore, it is necessary to coordinate each industry for this purpose. Third, through narrowing the gap between nominal tariff rate and effective tariff rate and through systemtizing the effective tariff rate at production stages, we can expect a structural change in industry.

      • 詩神에 대한 意識의 分裂 : William Blake's Poety (3) William Blake 論(3)

        姜通源 제주대학교 1984 논문집 Vol.18 No.1

        In history of English literature, romanticism is a tendency to seek an ideal aesthetic world in fancy and imagination and to express it in an individualized and sentimental form, appealing more to the needs of the emotions than to the reason. Romanticism therefore is a tendency toward inspiration and away from discipline (classicism) in the writer's approach to his materials. It is, further, a rebellion against whatever is orthodox and regulated; it is a rebellion against the past. William blake was one of the front-running poets of English romanticism. He was a painter and an engraver. He was also mystic and lived much of his time among his world of visions and spiritual communications. For that reson, some of his verse is hard to comprehend. But the bulk of his verse is as delightfully Iyric and imaginative as that of any of the romantic poets. His best poetry is contained in the two collections: Songs of Innocenceand Songs of Experience. By the way, before reaching the contrary poetic states or worlds of the two collections, we can see Blake's early poetry, simple and imaginative, written in his teens. It is Poetical Sketches, the first expressions and rational statements of the eighteenth century literature. In Poetical Sketches appear there some odes with other works, which have the romantic qulities, and they are odes of seasonal materials and concerning with the Muses. Now, the present writer has dealt with the problem of the Muses, making the three poems among them the subject of criticism. And so this paper has been a study of Blake's dissociated consciousness to the Muses,laying stress on the poems: "To the Muses," "To the Evening Star," and "To Morning,"

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