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        Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer

        Lee, K-S,Lee, Y-S,Lee, J-M,Ito, K,Cinghu, S,Kim, J-H,Jang, J-W,Li, Y-H,Goh, Y-M,Chi, X-Z,Wee, H,Lee, H-W,Hosoya, A,Chung, J-H,Jang, J-J,Kundu, J K,Surh, Y-J,Kim, W-J,Ito, Y,Jung, H-S,Bae, S-C Macmillan Publishers Limited 2010 Oncogene Vol.29 No.23

        Human lung adenocarcinoma, the most prevalent form of lung cancer, is characterized by many molecular abnormalities. K-ras mutations are associated with the initiation of lung adenocarcinomas, but K-ras-independent mechanisms may also initiate lung tumors. Here, we find that the runt-related transcription factor Runx3 is essential for normal murine lung development and is a tumor suppressor that prevents lung adenocarcinoma. Runx3−/− mice, which die soon after birth, exhibit alveolar hyperplasia. Importantly, Runx3−/− bronchioli exhibit impaired differentiation, as evidenced by the accumulation of epithelial cells containing specific markers for both alveolar (that is SP-B) and bronchiolar (that is CC10) lineages. Runx3−/− epithelial cells also express Bmi1, which supports self-renewal of stem cells. Lung adenomas spontaneously develop in aging Runx3+/− mice (∼18 months after birth) and invariably exhibit reduced levels of Runx3. As K-ras mutations are very rare in these adenomas, Runx3+/− mice provide an animal model for lung tumorigenesis that recapitulates the preneoplastic stage of human lung adenocarcinoma development, which is independent of K-Ras mutation. We conclude that Runx3 is essential for lung epithelial cell differentiation, and that downregulation of Runx3 is causally linked to the preneoplastic stage of lung adenocarcinoma.

      • KCI등재

        1H NMR Measurements of the Phase Transition of (NH₄)₃H(SO₄)₂ Single Crystals

        S. H. Choi,Moohee Lee,Ae Ran Lim,K. S. Han,S. K. Kwon,S. K. Nam 한국물리학회 2008 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.52 No.2

        $^1$H nuclear magnetic resonance (NMR) experiments have been performed in the temperature range of 30 -- 300 K at 7 T to investigate the phase-dependent nature of the dynamic network of hydrogen bonds in a ((NH₄)₃H(SO₄)₂ single crystal. The crystal has six phases, which are ferroelectric, antiferroelectric, incommensurate, antiferroelectric, ferroelastic, and superionic with the respective transition temperatures of 63, 133, 139, 256 and 413 K. The spin-lattice relaxation time, T₁, of ¹H NMR is similar for the ammonium protons and the hydrogen-bond protons over the entire range of experimental temperatures. The T₁, of ¹H NMR gradually decreases down to 120 K and starts to steeply increase below 100 K. Then, the T₁ shows an abrupt decrease below 68 K with a sharp minimum at 63 K, where the ferroelectric transition occurs. The ¹H NMR spectrum shifts to the high-frequency side at temperatures below 63 K due to the ferroelectric phase transition. This behavior of the T₁ and the spectrum confirms a dramatic change in the dynamics of hydrogen bonds associated with the ferroelectric phase transition at 63 K. $^1$H nuclear magnetic resonance (NMR) experiments have been performed in the temperature range of 30 -- 300 K at 7 T to investigate the phase-dependent nature of the dynamic network of hydrogen bonds in a ((NH₄)₃H(SO₄)₂ single crystal. The crystal has six phases, which are ferroelectric, antiferroelectric, incommensurate, antiferroelectric, ferroelastic, and superionic with the respective transition temperatures of 63, 133, 139, 256 and 413 K. The spin-lattice relaxation time, T₁, of ¹H NMR is similar for the ammonium protons and the hydrogen-bond protons over the entire range of experimental temperatures. The T₁, of ¹H NMR gradually decreases down to 120 K and starts to steeply increase below 100 K. Then, the T₁ shows an abrupt decrease below 68 K with a sharp minimum at 63 K, where the ferroelectric transition occurs. The ¹H NMR spectrum shifts to the high-frequency side at temperatures below 63 K due to the ferroelectric phase transition. This behavior of the T₁ and the spectrum confirms a dramatic change in the dynamics of hydrogen bonds associated with the ferroelectric phase transition at 63 K.

      • Relationship Between K<sub>trans</sub> and K<sub>1</sub> with Simultaneous Versus Separate MR/PET in Rabbits with VX2 Tumors

        Lee, K. H.,Kang, S. K.,Goo, J. M.,Lee, J. S.,Cheon, G. J.,Seo, S.,Hwang, E. J. INTERNATIONAL INSTITUTE OF ANTICANCER RESEARCH 2017 Anticancer research Vol.37 No.3

        <P>Background/Aim: To compare the relationship between Ktrans from DCE-MRI and K1 from dynamic (NNH3)-N-13- PET, with simultaneous and separate MR/PET in the VX-2 rabbit carcinoma model. Materials and Methods: MR/PET was performed simultaneously and separately, 14 and 15 days after VX-2 tumor implantation at the paravertebral muscle. The Ktrans and K-1 values were estimated using an in-house software program. The relationships between Ktrans and K-1 were analyzed using Pearson's correlation coefficients and linear/non-linear regression function. Results: Assuming a linear relationship, Ktrans and K-1 exhibited a moderate positive correlations with both simultaneous ( r=0.54-0.57) and separate ( r=0.53-0.69) imaging. However, while the Ktrans and K-1 from separate imaging were linearly correlated, those from simultaneous imaging exhibited a non-linear relationship. The amount of change in K-1 associated with a unit increase in Ktrans varied depending on Ktrans values. Conclusion: The relationship between K-trans and K-1 may be mis-interpreted with separate MR and PET acquisition.</P>

      • SCISCIESCOPUS

        Predicting temporal shifts in the spring occurrence of overwintered Scotinophara lurida (Hemiptera: Pentatomidae) and rice phenology in Korea with climate change

        Lee, H.,Kang, W. S.,Ahn, M. I.,Cho, K.,Lee, J. H. Springer Science + Business Media 2016 International journal of biometeorology Vol.60 No.1

        <P>Climate change could shift the phenology of insects and plants and alter their linkage in space and time. We examined the synchrony of rice and its insect pest, Scotinophara lurida (Burmeister), under the representative concentration pathways (RCP) 8.5 climate change scenario by comparing the mean spring immigration time of overwintered S. lurida with the mean rice transplanting times in Korea. The immigration time of S. lurida was estimated using an overwintered adult flight model. The rice transplanting time of three cultivars (early, medium, and medium-late maturing) was estimated by forecasting the optimal cultivation period using leaf appearance and final leaf number models. A temperature increase significantly advanced the 99 % immigration time of S. lurida from Julian day 192.1 in the 2000s to 178.4 in the 2050s and 163.1 in the 2090s. In contrast, rice transplanting time was significantly delayed in the early-maturing cultivar from day 141.2 in the 2000s to 166.7 in the 2050s and 190.6 in the 2090s, in the medium-maturing cultivar from day 130.6 in the 2000s to 156.6 in the 2050s and 184.7 in the 2090s, and in the medium-late maturing cultivar from day 128.5 in 2000s to 152.9 in the 2050s and 182.3 in the 2090s. These simulation results predict a significant future phenological asynchrony between S. lurida and rice in Korea.</P>

      • SCISCIESCOPUS

        Facile synthesis of an IRMOF-3 membrane on porous Al<sub>2</sub>O<sub>3</sub> substrate via a sonochemical route

        Lee, Y.R.,Cho, S.M.,Ahn, W.S.,Lee, C.H.,Lee, K.H.,Cho, W.S. Elsevier 2015 Microporous and mesoporous materials Vol.213 No.-

        A densely-packed IRMOF-3 membrane (S-IRMOF-3(Mem)), ~55 μm in thickness, on an Al<SUB>2</SUB>O<SUB>3</SUB> disc support was prepared via a sonochemical synthesis route, and the optimal fabrication conditions were established. Bare IRMOF-3 particles (S-IRMOF-3(p)) were synthesized independently to analyze the contribution of the Al<SUB>2</SUB>O<SUB>3</SUB> support. The overall physicochemical properties of the IRMOF-3 products produced via the sonochemical route were superior to those prepared by microwave heating. The IRMOF-3 materials produced were characterized by XRD, SEM, EDS-mapping, and N<SUB>2</SUB> adsorption-desorption measurements. S-IRMOF-3(p) exhibited satisfactory CO<SUB>2</SUB> adsorption capacities (54 mg/g at 298 K/1 bar; 732 mg/g at 298 K/20 bar) and CO<SUB>2</SUB>/N<SUB>2</SUB> selectivity (18 at 298 K/1 bar). Both S-IRMOF-3(Mem) and S-IRMOF-3(p) were assessed as a catalyst for a liquid phase Knoevenagel condensation reaction between benzaldehyde and ethyl cyanoacetate. S-IRMOF-3(Mem) and S-IRMOF-3(p) showed comparable conversions (87-89%) with 100% selectivity after a 4 h reaction at 333 K. The heterogeneous nature of the catalyst was confirmed by a hot filtering experiment, and S-IRMOF-3(Mem) could be recovered easily after the reaction and be recycled several times with little change in product yield.

      • 문학반응이론에 의한 보건의학기술계열 국가시험개선방안에 관한 연구

        이창규,이승관,조경진,박종성,정수경,유병서,박상숙,윤효숙,황선철,문경환,김정민,함용운,김지환,임국환,김영순,윤경희,황성준 高麗大學校 倂設 保健大學 保健科學硏究所 1998 保健科學論集 Vol.24 No.1

        The nationally-governed examinations for certification of allied health professions in Korea have been continued for thirty three years. During that time, there were a lot of managerial improvements in carrying out the examinations, for example, the looking-over the papers converted from manual method to computerized one. Nevertheless, the overall aspects of item management in the national examinations are still remained as obsolete style. In some developed countries they have already tried or adopted computerized system in making questions, executing item analysis, developing item banking, and in overall management of examinations, looking over papers for their national licensure examinations, and have established good reputations. Since the National Health Personnel Licensing Examination Board was established in 1998, now we can expect there would be a lots of improvements in the managerial systems and organizational structures associated with the national licensing examinations suggesting followings. 1. The contents and scope of the licensing examinations based on job analysis should be announced publicaly. 2. Items should be developed based on the scopes and contents of job characteristics. 3. All the developed items for the licensing examinations should be tested quantitatively prior to banking items. 4. All the parameters of the stored items should be fully estimated through item response theory. 5. All the efforts should be given in order to execute the examinations in individual residential areas on behalf of every examinee. 6. To the licensing examination system the Computerized Adaptive Testing system should be introduced in order to enhance the efficiencies. 7. Security enhancement on the stored items should be reminded in order to prevent leaking out the banking items. 8. Much more improvements should be made for the proper job evaluations. 9. Every efforts should be given to prevent cheatings encountable during the examinations. 10. Make the best of professional volunteers from the various fields in the execution of licensing examinations. 11. Consider a new system in that examinations can be executed twice or more in a year. 12. The current methods of presiding over the examinations should be replaced by a more reasonable one. 13. The results of the examinations should be announced as soon as possible in order not to prolong the examinees' unemployment periods. 14. The National Health Personnel Licensing Examination Board should try to rationalize the management keeping step with the information-oriented society.

      • Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II

        Lee, K,E,Kang, H‐,Y,Lee, S,K,Yoo, S,H,Lee, J‐,C,Hwang, Y‐,H,Nam, KH,Kim, J‐,S,Park, J‐,C,Kim, J‐,W Blackwell Publishing Ltd 2011 Clinical genetics Vol.79 No.4

        <P>Lee K‐E, Kang H‐Y, Lee S‐K, Yoo S‐H, Lee J‐C, Hwang Y‐H, Nam KH, Kim J‐S, Park J‐C, Kim J‐W. Novel dentin phosphoprotein frameshift mutations in dentinogenesis imperfecta type II.</P><P>The dentin sialophosphoprotein (<I>DSPP</I>) gene encodes the most abundant non‐collagenous protein in tooth dentin and DSPP protein is cleaved into several segments including the highly phosphorylated dentin phosphoprotein (DPP). Mutations in the <I>DSPP</I> gene have been solely related to non‐syndromic form of hereditary dentin defects. We recruited three Korean families with dentinogenesis imperfecta (DGI) type II and sequenced the exons and exon–intron boundaries of the <I>DSPP</I> gene based on the candidate gene approach. Direct sequencing of PCR products and allele‐specific cloning of the highly repetitive exon 5 revealed novel single base pair (bp) deletional mutations (c.2688delT and c.3560delG) introducing hydrophobic amino acids in the hydrophilic repeat domain of the DPP coding region. All affected members of the three families showed exceptionally rapid pulp chambers obliteration, even before tooth eruption. Individuals with the c.3560delG mutation showed only mild, yellowish tooth discoloration, in contrast to the affected individuals from two families with c.2688delT mutation. We believe that these results will help us to understand the molecular pathogenesis of DGI type II as well as the normal process of dentin biomineralization.</P>

      • SCISCIESCOPUS

        S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

        Yi, S.,Um, S.,Lee, J.,Yoo, J.,Bang, S.,Park, E.,Lee, M.,Nam, K.,Jeon, Y.,Park, J.,You, J.,Lee, S.J.,Bae, G.U.,Rhie, J.,Kozma, Sara C.,Thomas, G.,Han, J.W. Cell Press 2016 Molecular Cell Vol.62 No.3

        S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

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