• Title/Summary/Keyword: initiation step

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Two distinct nodes of translational inhibition in the Integrated Stress Response

  • Ryoo, Hyung Don;Vasudevan, Deepika
    • BMB Reports
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    • v.50 no.11
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    • pp.539-545
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    • 2017
  • The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.

Comparison of Current GCPs on the Basis of the Contents in ICH-GCP (ICH-GCP와 선진 각국의 GCP 비교)

  • 박혜연
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.11a
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    • pp.57-74
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    • 1997
  • To make a proposal for the revision of KGCP, ICH Harmonized Tripartite Guideline for Good Clinical Practice, which is on the stage of worldwide implementation, was compared with current GCPs of tripartite countries of ICH, namely USA, Europe and Japan as well as Korea. On the basis of the classification in ICH GCP, comprehensive comparisons among the corresponding articles of 4 regions or countries were made in the order of IRB / IEC, Investigator, Sponsor and Clinical Trial Protocol. Based on the comparisons of the contents in ICH-GCP with those in current GCPs, major suggestions for the revision of current KGCP can be made as follows. Firstly, the function of IRB / IEC needs to be strengthened for the initiation and continuation of clinical trial. Current 2-step approval system of IRB / IEC and Health Authorities requires to be converted into the system similar to that of developed countries. Secondly, sponsor's obligation needs to be tightened to control and assure the quality of clinical trial. Inspection of regulatory authorities should be made to perform during and / or after clinical trial, when it is necessary. In other words, sponsor should be made to establish written Standard Operating Procedures (SOPs) for all aspects of clinical trial including monitoring to ensure that trials are conducted and data are generated, documented, and reported in compliance with the protocol, GCP, and the applicable regulatory requirement (s). Besides, the provision of ‘Quality Control and Quality Assurance’ should be added to the protocol to establish the credibility of the result of the clinical trial.

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Effects of Punica granatum L. Fractions on Quinone Reductase Induction and Growth Inhibition on Serveral Cancer Cells (석류 추출성분이 암세포 증식 억제와 Quinone Reductase 유도활성에 미치는 효과)

  • 심선미;최상원;배송자
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.30 no.1
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    • pp.80-85
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    • 2001
  • Various lines of evidence suggest that dietary components protect the initiation step of carcinogenesis. In this study, the ethylacetate (PGMEA), ethylether (PGMEE), butanol (PGMB) and aqueous (PGMA) soluble fractions of Punica granatum L. (PG) were screened for their growth inhibition using the MTT assay on HepG2, HeLa, C6, MCF-7 and HT-29 cells and for their activity to induce quinone reductase (QR) in HepG2 cells. Among various fractions of Punica granatum L., the PGMEE showed the strongest growth inhibition at 500 $\mu\textrm{g}$/mL which resulted 92.5% on Hela cell lines and 97.8% on C6 cell lines. The PGMEA and PGMB also showed significant growth inhibition. The assay of QR induction on HepG2 cells, grown in the presence of PGMEE at the concentration of 50$\mu\textrm{g}$/mL, was 1.4 times more effective compared with the control value of1.0. These results suggested that useful cancer chemoprevention materials could be isolated from PGMEE fraction of Punica granatum L.

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PelB Signal Sequence로 유도된 재조합 인간 상피세포 증식인자 분비 발현 벡터의 제조

  • Park, Se-Cheol;Nam, Jung-Hyun;Kim, Jeong-Keun;Kwon, Tae-Jong;Ko, In-Young;You, Kwang-Hyun
    • Microbiology and Biotechnology Letters
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    • v.24 no.5
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    • pp.553-559
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    • 1996
  • We have designed nucleotide sequences of hEGF structural gene to eliminate the N-terminal methionine residue incorporated during the translation initiation step, and constructed recombinant human epidermal growth factor (rhEGF) secretion plasmids pYHB101, and pYHB2 in which pelB signal sequence-hEGF gene was expressed under the control of the T7, and tac promoter, respectively. We also constructed pYHB1 vector which contains rhEGF gene controlled by T7 promoter. The transformant with pYHB101 showed relatively slow growth pattern compared to the transformant with pYHB1. However, we observed that the transformant with pYHB101 secreted rhEGF of 13 mg/l significantly after 5 hr induction with 1 mM IPTG and that the T7 promoter was more effective than tac promoter when connected to pelB signal sequence. The amount of rhEGF was 14 mg/l under the sub-optimized condition.

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Radical Polymerization of Methyl Methacrylate with Tricaprylmethylammonium Chloride (Tricaprylmethylammonium Chloride에 의한 Methyl Methacrylate의 라디칼 중합)

  • Park, Sang-Wook;Moon, Jin-Bok;Ha, Yoo-Su;Kim, Jong-Hyeon
    • Applied Chemistry for Engineering
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    • v.4 no.2
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    • pp.300-307
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    • 1993
  • The phase-transfer polymerization of methyl methacrylate with tricaprylmethylammonium chloride-$Na_2S_2O_4-CCl_4$ initiator system was investigated in an aqueous-organic two-phase system. The observed rates of polymerization were compared with those obtained from the polymerization mechanism proposed with a cyclic phase-transfer initiation step. The rate of polymerization was found to be proportional to the concentration of $Q^+$ and square root of ${S_2O_4}^{-2}$ in the aqueous solution and the feed quantity of $CCl_4$ and MMA.

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First-principles Study on the Formation of Solid-Electrolyte Interphase on the LiMn2O4 Cathode in Li-Ion Batteries (제일원리 전산모사를 통한 리튬 이온 전지의 LiMn2O4 전극-전해질 계면 반응 분석)

  • Choe, Dae-Hyeon;Gang, Jun-Hui;Han, Byeong-Chan
    • Proceedings of the Korean Institute of Surface Engineering Conference
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    • 2016.11a
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    • pp.97-97
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    • 2016
  • Development of advanced Li-ion battery cells with high durability is critical for safe operation, especially in applications to electric vehicles and portable electronic devices. Understanding fundamental mechanism on the formation of a solid-electrolyte interphase (SEI) layer, which plays a substantial role in the electrochemical stability of the Li-ion battery, in a cathode was rarely reported unlike in an anode. Using first-principles density functional theory (DFT) calculations and ab-initio molecular dynamic (AIMD) simulations we demonstrate atomic-level process on the generation of the SEI layer at the interface of a carbonate-based electrolyte and a spinel $LiMn_2O_4$ cathode. To accomplish the object we calculate the energy band alignment between the work function of the cathode and frontier orbitals of the electrolyte. We figure out that a proton abstraction from the carbonate-based electrolyte is a critical step for the initiation of an SEI layer formation. Our results can provide a design concept for stable Li-ion batteries by optimizing electrolytes to form proper SEI layers.

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The Analysis of Water Tree Degradations in Underground Distribution Cables Using Image Measurement (가교폴리에틸렌 지중케이블에서 화상계측을 이용한 수트리 열화현상 분석)

  • Kim, Duck-keun;Lim, Jang-Seob;Lee, Jin;Lee, Joon-Ung;Kim, Tae-Sung
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 1998.06a
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    • pp.19-23
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    • 1998
  • Water tree degradations have been considered as one of the most important causes of failure in underground distribution cables with polymeric insulation. Water tree growth is a preliminary step in the sequence of electrical tree initiation and electrical breakdown of the insulation. In this paper, needle electrode is made use of the etching methods and the pellet type specimen is made to observe the water tree in succession. In previous methods are able to observe the tree degradations without cutting and dyeing. The water tree image is recorded on VTR with CCD camera. The tree length of X, Y axis direction and aging area(treeing area) are calculated with image measurement. As a result of this study, water tree is observed by non-destructive method. Electrical tree is initiated from needle electrode tip only but water tree is initiated from total area of water electrode. Electrical tree owing to water treeing is initiated at low electric field and grown with discontinuously. Namely, water tree is shown up a different characteristics of tree growth.

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Microbial Degradation of Monohydroxybenzoic Acids

  • Kim, Chi-Kyung;Tim
    • Journal of Microbiology
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    • v.38 no.2
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    • pp.53-61
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    • 2000
  • Hydroxybenzoic acids are the most important intermediates in the degradative pathways of various aromatic compounds. Microorganisms catabolize aromatic compounds by converting them to hydroxylated intermediates and then cleave the benzene nucleus with ring dioxygenases. Hydroxylation of the benzene nucleus of an aromatic compound is an essential step for the initiation and subsequent disintegration of the benzene ring. The incorporation of two hydroxyl groups is essential for the labilization of the benzene nucleus. Monohydroxybenzoic acids such as 2-hydroxybenzoic acid, 3-hydroxybenzoic acid, and 4-hydrosybenzoic acid, opr pyrocattechuic acid that are susceptible for subsequent oxygenative cleavage of the benzene ring. These terminal aromatic intermediates are further degraded to cellular components through ortho-and/or meta-cleavage pathways and finally lead to the formation of constituents of the TCA cycle. Many groups of microorganisms have been isolated as degraders of hydroxybenzoic acids with diverse drgradative routes and specific enzymes involved in their metabolic pahtway. Various microorganisms carry out unusual non-oxidative decarboxylation of aromatic acids and convert them to respective phenols which have been documented. Futher, Pseudomonas and Bacillus spp. are the most ubiquitous microorganisms, being the principal components of microflora of most soil and water enviroments.

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Functional Implications in Apoptosis by Interferon Inducible Gene Product 1-8D, the Binding Protein to Adenovirus Preterminal Protein

  • Joung, In-Sil;Angeletti, Peter C.;Engler, Jeffrey A.
    • Journal of Microbiology
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    • v.41 no.4
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    • pp.295-299
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    • 2003
  • Adenovirus (Ad) precursor to the terminal protein (pTP) plays an essential roles in the viral DNA replication. Ad pTP serves as a primer for the synthesis of a new DNA strand during the initiation step of replication. In addition, Ad pTP forms organized spherical replication foci on the nuclear matrix (NM) and anchors the viral genome to the NM. Here we identified the interferon inducible gene product 1-8D (Inid) as a pTP binding protein by using a two-hybrid screen of a HeLa cDNA library. Of the clones obtained in this assay, nine were identical to the Inid, a 13-kDa polypeptide that shares homology with genes 1-8U and Leu-13/9-27, most of which have little known functions. The entire open reading frame (ORF) of Inid was cloned into the tetracycline inducible expression vector in order to determine the biological functions related with adenoviral infection. When Inid was introduced to the cells along with adenoviruses, fifty to sixty percent of Ad-infected cells expressing Inid had rounded morphology, which was suggestive of apoptosis. Results from the terminal deoxynucleotidyl transferase (TdT) and DNA fragmentation assays confirmed that Inid induces apoptosis in Ad-infected or in uninfected cells. The Inid binding to pTP may target the cell for apoptotic destruction as a host defense mechanism against the viral infection.

Extraction of Cooperation Factors and Development of Cooperation Program for Unified Cooperative Forest Management - A Case Study of the East Coast & Mt. Jiri Sphere Forest Fire Administration Center - (통합 산림관리를 위한 협력요인 추출 및 협력프로그램 개발 - 동해안 및 지리산권역 산불관리센터의 사례를 중심으로 -)

  • Kim, Eui-Gyeong;Kim, Seong-Ju;Kim, Hyeon-Geun;Kim, Dae-Hyun
    • Journal of Korean Society of Forest Science
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    • v.96 no.6
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    • pp.684-692
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    • 2007
  • The object of this study is to identify the factors that is making and promoting cooperation for the unified forest fire administration, and then introduce cooperation process and cooperation manual for an effective forest management. For this purpose, the case studies were carried about "The East Coastal Forest Fire Administration Center" and "The Forest Fire Administration Center in Mt. Jiri Area" to have obtained excellent results by cooperation among administrative districts, and cooperative factors were extracted through analyzing each steps. That is, cooperation steps were divided into 4 steps of Initiation, Planning, Implementation, Benefiting, and in-depth interview and questionnaires were carried for extracting cooperation factors by each step for the unified cooperative forest management system. And with AHP analysis, essential four factors were extracted by each step based on priority order. Finally with the base of the essential 4 factors by each step, the cooperation process and manual appliable to forestry cooperation project were developed. This will be a guideline in order to achieve successful forest administrations through the cooperation among local administrative governments.