Cooperativity of E-cadherin and Smad4 Loss to Promote Diffuse-Type Gastric Adenocarcinoma and Metastasis

Park, Jun Won,Jang, Seok Hoon,Park, Dong Min,Lim, Na Jung,Deng, Chuxia,Kim, Dae Yong,Green, Jeffrey E.,Kim, Hark Kyun American Association for Cancer Research 2014 Molecular Cancer Research Vol.12 No.8

<P>Loss of E-cadherin (<I>CDH1</I>), Smad4, and p53 has been shown to play an integral role in gastric, intestinal, and breast cancer formation. Compound conditional knockout mice for Smad4, p53, and E-cadherin were generated to define and compare the roles of these genes in gastric, intestinal, and breast cancer development by crossing with <I>Pdx-1-Cre</I>, <I>Villin-Cre</I>, and <I>MMTV-Cre</I> transgenic mice. Interestingly, gastric adenocarcinoma was significantly more frequent in <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1<SUP>F</SUP></I><SUP>/+</SUP> mice than in <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1</I><SUP>+/+</SUP> mice, demonstrating that <I>Cdh1</I> heterozygosity accelerates the development and progression of gastric adenocarcinoma, in combination with loss of Smad4 and p53. <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1<SUP>F</SUP></I><SUP>/+</SUP> mice developed gastric adenocarcinomas without E-cadherin expression. However, intestinal and mammary adenocarcinomas with the same genetic background retained E-cadherin expression and were phenotypically similar to mice with both wild-type <I>Cdh1</I> alleles. Lung metastases were identified in <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1<SUP>F</SUP></I><SUP>/+</SUP> mice, but not in the other genotypes. Nuclear β-catenin accumulation was identified at the invasive tumor front of gastric adenocarcinomas arising in <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1<SUP>F</SUP></I><SUP>/+</SUP> mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the inhibition of β-catenin signaling by E-cadherin or Smad4 downregulates signaling pathways involved in metastases in <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1<SUP>F</SUP></I><SUP>/+</SUP> mice. Knockdown of β-catenin significantly inhibited the migratory activity of <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1<SUP>F</SUP></I><SUP>/+</SUP> cell lines. Thus, loss of E-cadherin and Smad4 cooperates with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human gastric adenocarcinoma.</P><P><B>Implications:</B> This study demonstrates that inhibition of β-catenin is a converging node for the antimetastatic signaling pathways driven by E-cadherin and Smad4 in <I>Pdx-1-Cre;Smad4<SUP>F/F</SUP>;Trp53<SUP>F/F</SUP>;Cdh1<SUP>F</SUP></I><SUP>/+</SUP> mice, providing novel insights into mechanisms for gastric cancer metastasis. <I>Mol Cancer Res; 12(8); 1088–99. ©2014 AACR</I>.</P>

Development of Escherichia coli MG1655 strains to produce long chain fatty acids by engineering fatty acid synthesis (FAS) metabolism

Jeon, E.,Lee, S.,Won, J.I.,Han, S.O.,Kim, J.,Lee, J. IPC Science and Technology Press ; Elsevier Scienc 2011 Enzyme and microbial technology Vol.49 No.1

The goal of this research was to develop recombinant Escherichia coli to improve fatty acid synthesis (FAS). Genes encoding acetyl-CoA carboxylase (accA, accB, accC), malonyl-CoA-[acyl-carrier-protein] transacylase (fabD), and acyl-acyl carrier protein thioesterase (EC 3.1.2.14 gene), which are all enzymes that catalyze key steps in the synthesis of fatty acids, were cloned and over-expressed in E. coli MG1655. The acetyl-CoA carboxylase (ACC) enzyme catalyzes the addition of CO<SUB>2</SUB> to acetyl-CoA to generate malonyl-CoA. The enzyme encoded by the fabD gene converts malonyl-CoA to malonyl-[acp], and the EC 3.1.2.14 gene converts fatty acyl-ACP chains to long chain fatty acids. All the genes except for the EC 3.1.2.14 gene were homologous to E. coli genes and were used to improve the enzymatic activities to over-express components of the FAS pathway through metabolic engineering. All recombinant E. coli MG1655 strains containing various gene combinations were developed using the pTrc99A expression vector. To observe changes in metabolism, the in vitro metabolites and fatty acids produced by the recombinants were analyzed. The fatty acids (C16) from recombinant strains were produced 1.23-2.41 times higher than that from the wild type.

장애 성인의 평생교육에 대한 인식 : E시를 중심으로

박은혜,원종례,김주영,최옥이 국립특수교육원 2007 특수교육연구 Vol.14 No.1

최근 생애 전 주기에 걸친 장애인의 교육에 대한 관심이 높아지고 있으나 구체적인 연구는 많이 이루어지지 않았으며, 발달장애 성인을 중심으로 논의되고 있다. 이에 본 연구에서는 2004년 평생학습도시로 선정된 경기도 E 시의 성인장애인 395명을 대상으로 설문조사를 통하여 평생교육에 대한 인식을 조사 ·분석하였다. 그 결과는 크게 (1) E 시의 장애인 복지 행정에 대한 만족도, (2) 장애인 복지 행정 중 노력해야 할 분야, (3) 평생학습 프로그램 참여, (4) 평생학습 프로그램 개설 분야로 나누어 장애 유형과 연령, 거주 형태별로 제시하였다. 감각장애 및 신체장애를 포함하여 모든 장애영역의 성인들을 대상으로 하였으며, 일반인을 위한 평생교육 인프라가 비교적 잘 구축된 곳에서의 장애인들의 요구 및 인식을 조사하여 분석한 점에서 본 연구의 의의를 찾을 수 있을 것이다. Recently, the importance and necessity of life-long education has been emphasized in special education and rehabilitation field. Number of studies regarding life-long education for people with disabilities is still very limited and most of the published studies focused on the people with developmental disabilities. In this study, we surveyed 395 adults with various disabilities who lived in E city regarding their perception and needs of community life-long education programs. Results included that 1) a majority of the respondents were not aware of their city's well-established life-long programs for citizens, and wanted to participate their community's life-long education programs if provided for them and notified for them, 2) financial support such as medical and/or rehabilitation support was highly ranked, and also cultural/artistic programs were raked higher than vocational programs. Implications of this study was discussed.

A Computer Simulation of the Four Charm Production and Fragmentation in e+e- Collisions

E. Won,Daekyoung Kang,H.C. Ha,J.H. Choi 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.48 No.II

Theoretical predictions of the rate of exclusive production of two charmonia in e+e. annihilation differ significantly from measurements by the Belle collaboration. Up to now, there has been no conclusive explanation for this substantial discrepancy. However, recent theoretical works have suggested that it may be possible to identify the origin of the discrepancy from a study of four charm inclusive events. We present necessary computational steps required for such an experimental study at B factories. Event generation of the reaction e+e. ! c.cc.c and the fragmentation of charm quarks are simulated. These two important computational steps provide all the information necessary to measure the total cross section of the four charm hadron final state at B factories.

Heterologous Expression of Human SLC1A5v2 as a Functional Glutamine Transporter in Escherichia coli

Kim E Young,Park Ji Won,김옥빈 한국미생물·생명공학회 2023 한국미생물·생명공학회지 Vol.51 No.1

Neutral and non-essential amino acid, glutamine (Gln), plays an essential role in supplying nitrogen to all the amino acids and nucleotides in the mammalian body. Gln is also the most important carbon source that provides intermediates for gluconeogenesis and fatty acid synthesis and supplements the tricarboxylic acid cycle in fast-growing cancer cells. Among the known 14 Gln transporter genes, soluted carrier family 1 member 5 (SLC1A5) has been reported to be closely associated with cancer cell growth. Three variants (v1, v2, and v3) have been derived from SLC1A5. Here, we established a heterologous gene expression system for the active form of human SLC1A5 variant-2 (hSLC1A5v2) in Escherichia coli. v2 is the smallest variant that has not yet been studied. Four expression systems were investigated: pBAD, pCold, pET, and pQE. We also addressed the problem of codon usage bias. Although pCold and pET overexpressed hSLC1A5v2 in E. coli, they were functionally inactive. hSLC1A5v2 using the pBAD system was able to catalyze the successful transport of Gln, even if it was not highly expressed. Initial activity of hSLC1A5v2 for [14C] Gln uptake in E. coli reached up to 6.73 μmole·min-1·gDW-1 when the cell was induced with 80 mM L-arabinose. In this study, we demonstrated a heterologous expression system for the human membrane protein, SLC1A5, in E. coli. Our results can be used for the functional comparison of SLC1A5 variants (v1, v2, and v3) in future studies, to facilitae the developement of SLC1A5 inhibitors as effective anticancer drugs.

Sulfonated Poly(arylene sulfide sulfone nitrile) Multiblock Copolymers with Ordered Morphology for Proton Exchange Membranes

Shin, Dong Won,Lee, So Young,Lee, Chang Hyun,Lee, Kwan-Soo,Park, Chi Hoon,McGrath, James E.,Zhang, Mingqiang,Moore, Robert B.,Lingwood, Mark D.,Madsen, Louis A.,Kim, Young Taek,Hwang, Inchul,Lee, Youn American Chemical Society 2013 Macromolecules Vol.46 No.19

<P>Ordered morphologies in disulfonated poly(arylene sulfide sulfone nitrile) (SPSN) copolymers were generated via thermal annealing followed by multiblock copolymer synthesis. While SPSN random copolymers (R-SPSN) showed featureless morphologies, the SPSN multiblock copolymers (B-SPSN) exhibited cocontinuous lamellar morphologies with a center-to-center interdomain size of up to 40 nm. In spite of the well-ordered, interconnected hydrophilic domains, the water self-diffusion coefficient (e.g., <I>D</I> = (0.7–2.0) × 10<SUP>–10</SUP> m<SUP>2</SUP> s<SUP>–1</SUP>) and proton conductivity (e.g., σ = 0.16–0.20 S cm<SUP>–1</SUP> in deionized water at 30 °C) through B-SPSN were lower than those of the corresponding R-SPSN (e.g., <I>D</I> = (3.5–3.9) × 10<SUP>–10</SUP> m<SUP>2</SUP> s<SUP>–1</SUP> and σ = 0.21 S cm<SUP>–1</SUP>) due to the relatively lower water uptake of the B-SPSN after thermal annealing. The reduced water uptake of B-SPSN was beneficial to reduction of peroxide degradation rate. Thermal annealing produced significant gains in morphological ordering and finer control over desired membrane properties for proton conduction applications.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/mamobx/2013/mamobx.2013.46.issue-19/ma400889t/production/images/medium/ma-2013-00889t_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ma400889t'>ACS Electronic Supporting Info</A></P>

Mitral Annular Tissue Velocity Predicts Survival in Patients With Primary Mitral Regurgitation

You-Jung Choi,Chan Soon Park,Tae-Min Rhee,Hyun-Jung Lee,Hong-Mi Choi,In-Chang Hwang,Jun-Bean Park,Yeonyee E. Yoon,Jin Oh Na,Hyung-Kwan Kim,Yong-Jin Kim,Goo-Yeong Cho,Dae-Won Sohn,Seung-Pyo Lee The Korean Society of Cardiology 2024 Korean Circulation Journal Vol.54 No.6

Background and Objectives: Early diastolic mitral annular tissue (e') velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e' velocity in patients with mitral regurgitation (MR). Methods: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. According to the current guidelines, the cut-off value of e' velocity was defined as 7 cm/s. Results: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e' velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634-0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477-0.998; p=0.049). Abnormal e' velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170-5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189-21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e' velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308-0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680-1.356; p<0.001). Conclusions: In patients aged <65 years with primary MR, e' velocity served as an independent predictor of all-cause and cardiovascular deaths.

瑜伽師地論 : 우리말 飜譯案

元義範 동국대학교 불교대학 1971 東國思想 Vol.6 No.-

여기서 사용한 범본은 Vidgushekhara bhattachrya에 의하여 편집되고 Calcutta대학교에서 1957년에 발행한 Yoga­gca­ra bhu­mih이고 한문본은 고려대장경의 유가사지론이다. 이 범본의 편집자는 유가사지론을 무자의 저술로 인정하고 있다. 논부를 우리말로 옮기는데 어떤 암시적인 도움이 여기서 발견될 수도 있지 않을까 하여 그 조그만 안을 내 본다. 먼저 초안으로서의 글귀나 절 또는 줄을 하나씩 떼어서 1번에 범문, 2번에 우리말 직역, 3번에 우리말 의역, 4번에 한문의 순서로 하고 글귀나 절, 줄을 떼어 쓰는 기준을 범문에 두었다. 일본 대동경출판사장판 국역일절경은 참조만 하였는데 본안에서 취급된 부분에서 일본역에서 좀 애매하게 번역되었다고 생각되는 곳은 한곳을 주를 달아서 밝혀 보았다. 결국 통틀어 잡아서 이렇게 번역될 수 밖에 별다른 도리가 없다고 생각되는 번역 말하자면 우리말 표준번역을 맨끝에 한데 묶어서 붙였다.

宗敎와 政治 : 不殺生戒와 戰爭을 中心으로

元義範 동국대학교 불교대학 1975 東國思想 Vol.8 No.-

佛敎認識論理學 : 序論

元義範 東國大學校 1967 論文集 Vol.3-4 No.-

The ultimate aim of Buddhist Logic is to get BODHI. It claims not only to be the natural and general logic of the human understanding(laukikajn~a￣na) but also to be the super natural and special logic of Buddha's understanding (lokottarajn~a￣na). Buddhist logic contains a theory on the direct perception (pratyaksa) and s theory on inferences (anuma￣na) as the Western Logic, and Buddha's wisdom (Buddhasamjn~a) Buddha's wisdom is empirical and transcendental. In this sense, the logic of the Buddhists is an empiricism as well as a trascendentalism. By the natural and general understanding, human is limited to know only the natural side of the supernatural reality. Buddha's wisdom is not anti-natural but supernatural. By it, the supernatural side of the reality is known to Buddha. There are two kinds of knowledge in general: the natural knowledge and the supernatural knowledge. The natural knowledge consists of the two sub-kinds of knowledge: the direct knowledge and the indirect knowledge. The natural knowledge is called A￣layavijn~a￣na in Buddhist Logic. A￣layavijn~a￣na is a dynamic flow (santa￣na) of the moment (ksana) of self-consciousness generated by karma of adherence (a￣da￣nasmjn~a). The moment of self-consciousness has the subjective side (vijn~aptika) and the objective side (pratyaksa). The objective side consists of the two extremes: the physical body (upa￣da￣na) with sense organs (indriya) and the external world (sta￣na). The moment of self-consciousness with all the subjective and objective components of it repeats birth and death momentarily. The subject side (vijn~aptika) of the present moment shocked by its objective side (pratyaksa) reflects its previous moment through the remenberence (smrti) generated by karma, and constructs a conceptional judgement (kalpana) that "This (the present moment) is that (the previous moment). (So'yam)" This judgement is a knowledge. There is no real identity between 'This (the present moment)' and 'that (the previous moment).' Vijn~aptika conceires such a vague concept of identity by a￣da￣nasamjn~a. There is no continuity between the present moment and the prerious moment. They are quite different. Only the present moment is real. A￣rya Maitreya, therefore, said, "Abhuta pari kalpo'sti dvaamytatra nasti". (Madhya￣nta vibha￣ga s˙a￣stra)