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      • SCISCIESCOPUS

        Phosphorylation by NLK inhibits YAP ‐14‐3‐3‐interactions and induces its nuclear localization

        Moon, Sungho,Kim, Wantae,Kim, Soyoung,Kim, Youngeun,Song, Yonghee,Bilousov, Oleksii,Kim, Jiyoung,Lee, Taebok,Cha, Boksik,Kim, Minseong,Kim, Hanjun,Katanaev, Vladimir L,Jho, Eek‐,hoon unknown 2017 EMBO reports Vol.18 No.1

        <P>Hippo signaling controls organ size by regulating cell proliferation and apoptosis. Yes-associated protein (YAP) is a key downstream effector of Hippo signaling, and LATS-mediated phosphorylation of YAP at Ser127 inhibits its nuclear localization and transcriptional activity. Here, we report that Nemo-like kinase (NLK) phosphory-lates YAP at Ser128 both in vitro and in vivo, which blocks interaction with 14-3-3 and enhances its nuclear localization. Depletion of NLK increases YAP phosphorylation at Ser127 and reduces YAP-mediated reporter activity. These results suggest that YAP phosphorylation at Ser128 and at Ser127 may be mutually exclusive. We also find that with the increase in cell density, nuclear localization and the level of NLK are reduced, resulting in reduction in YAP phosphorylation at Ser128. Furthermore, knockdown of Nemo (the Drosophila NLK) in fruit fly wing imaginal discs results in reduced expression of the Yorkie (the Drosophila YAP) target genes expanded and DIAP1, while Nemo overexpression reciprocally increased the expression. Overall, our data suggest that NLK/Nemo acts as an endogenous regulator of Hippo signaling by controlling nuclear localization and activity of YAP/Yorkie.</P>

      • Regulation of transferrin recycling kinetics by PtdIns[4,5]P <sub>2</sub> availability

        Kim, Sunyun,Kim, Hyunmyung,Chang, Belle,Ahn, Namhui,Hwang, Suha,Di Paolo, Gilbert,Chang, Sunghoe,Kim, Sunyun,Kim, Hyunmyung,Chang, Belle,Ahn, Namhui,Hwang, Suha,Di Paolo, Gilbert,Chang, Sunghoe Federation of American Society for Experimental Bi 2006 The FASEB Journal Vol.20 No.13

        <P>Phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) is a phosphoinositide involved in a variety of cellular functions, including signal transduction, organelle trafficking, and actin dynamics. Although the role of PtdIns[4,5]P2 in endocytosis is well established, the precise trafficking steps relying on normal PtdIns[4,5]P2 balance in the endosomal pathway have not yet been elucidated. Here we show that decrease in intracellular PtdIns[4,5]P2 levels achieved by the overexpression of the 5-phosphatase domain of synaptojanin 1 or by siRNA knock-down of PIP5Ks expression lead to severe defects in the internalization of transferrin as well as in the recycling of internalized transferrin back to the cell surface in COS-7 cells. These defects suggest that PtdIns[4,5]P2 participates in multiple trafficking and/or sorting events during endocytosis. Coexpression of the PtdIns[4,5]P2 synthesizing enzyme, PIP5KI gamma, was able to rescue these endocytic defects. Furthermore, decreased levels of PtdIns[4,5]P2 caused delays in rapid and slow membrane recycling pathways as well as a severe backup of endocytosed membrane. Taken together, our results demonstrate that PtdIns[4,5]P2 availability regulates multiple steps in the endocytic cycle in non-neuronal cells.</P>

      • SCISCIESCOPUS

        Pt-doped Ni-silicide films formed by pulsed-laser annealing: Microstructural evolution and thermally robust Ni<sub>1-x</sub>Pt<sub>x</sub>Si<sub>2</sub> formation

        Kim, Jinbum,Shin, Ilgyou,Park, Taejin,Kim, Jinyong,Choi, Seongheum,Lee, Sungho,Hong, Seongpyo,Lee, Hyung-Ik,Won, Jung Yeon,Kim, Taegon,Kim, Yihwan,Hwang, Kihyun,Lee, Hoo-Jeong,Kim, Hyoungsub Elsevier 2019 JOURNAL OF ALLOYS AND COMPOUNDS Vol.788 No.-

        <P><B>Abstract</B></P> <P>Pulsed-laser annealing (PLA) was performed on a preformed Pt-doped Ni-rich silicide film (Ni<SUB>2</SUB>Si phase), and its microstructural and phase evolution were studied from submelting to melting condition by varying the laser power density (<I>P</I>). Vertically nonuniform compositional profile with an interfacial intermixing was observed under a solid state reaction regime (<I>P</I> < 400 mJ/cm<SUP>2</SUP>) due to a limited atomic diffusion. At higher <I>P</I> condition, melting/resolidification occurred with a continuous increase in the Si concentration, and various microstructures of the film evolved with increasing <I>P</I>: amorphous structure and nucleation/growth of NiSi and NiSi<SUB>2</SUB> phases form in that order on the Si interface. Lastly, by applying additional rapid thermal annealing on the polycrystalline mixture of NiSi and NiSi<SUB>2</SUB> phases formed by PLA, a uniform Pt-doped NiSi<SUB>2</SUB> film with strong epitaxial growth tendency on the Si(001) substrate and high thermal stability (up to 900 °C) was synthesized.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Pt-doped Ni-silicides are formed using pulsed-laser annealing at various powers. </LI> <LI> Power-dependent solid- and liquid-state reactions yield various microstructures. </LI> <LI> Power-dependent microstructural and phase evolution paths are suggested. </LI> <LI> Additional rapid thermal annealing forms a thermally stable NiSi<SUB>2</SUB> film. </LI> </UL> </P>

      • KCI등재

        Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites

        Kim Kangjin,Lee Sanghun,Park Sang-Chul,Kim Nam-Eun,Shin Chol,Lee Seung Ku,Jung Youngae,Yoon Dankyu,Kim Hyeonjeong,Kim Sanghyun,Hwang Geum-Sook,Won Sungho 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (β = −189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = −0.0938 and −0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (β = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels.

      • Functional fusion proteins and prevention of electrode fouling for a sensitive electrochemical immunosensor

        Kim, A-Ram,Park, Tae Jung,Kim, Minseok S.,Kim, In-Ho,Kim, Ki-Suk,Chung, Kwang Hoe,Ko, Sungho Elsevier 2017 Analytica chimica acta Vol.967 No.-

        <P><B>Abstract</B></P> <P>A highly sensitive electrochemical immunosensor was developed by preventing electrode fouling and using a novel fusion protein of silica binding polypeptides (SBP)-protein G (ProG) created by recombinant DNA technology as a functional crosslinker for rapid and self-oriented immobilization of antibodies onto silica nanoparticles (SiNPs). Antibody immobilization onto the SiNPs by the SBP-ProG could rapidly be achieved without any chemical treatment. The immunosensor was fabricated through bonding of a partially gold-deposited cyclic olefin copolymer (COC) (top substrate) and gold patterned interdigitated array COC electrode (bottom substrate). To prevent electrode fouling, human immunoglobulin G (hIgG) was immobilized onto the ceiling inside the microchannel, instead of the bottom electrode. Alkaline phosphatase (AP)-labeled anti-hIgG was allowed to immunoreact with hIgG on the ceiling, followed by addition of an enzyme to generate an oxidative peak current. A three-fold increase in current was observed from the immunosensor without any electrode fouling compared with a control with the protein functionalized electrode. Also, the SiNPs facilely coated with AP-anti-hIgG via the SBP-ProG could increase the electrochemical signal up to 20% larger than that of the AP-anti-hIgG alone. Furthermore, this immunosensor was ultrasensitive with a detection limit of 0.68 pg/mL of a biomarker associated with prostate cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A novel fusion protein was developed as crosslinker for rapid self-oriented immobilization of antibody on SiNPs. </LI> <LI> This crosslinker contributed to easy formation of SiNPs/Ab complexes, resulting in electrochemical signal enhancement. </LI> <LI> Novel prevention method of electrode fouling was developed to enhance sensitivity of the electrochemical immunosensor. </LI> <LI> This immunosensor exhibited excellent sensitivity with the simple fabrication methods. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • KCI등재

        Trametinib activates endogenous neurogenesis and recovers neuropathology in a model of Alzheimer’s disease

        Kim Mi-Yeon,Kim Mi Jeong,Lee Changyeob,Lee Juwon,Kim Sang Seong,Hong Sungho,Kim Hyoung Tae,Seo Jinsoo,Yoon Ki-Jun,Han Sungho 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

        Enhancing adult neurogenesis in the brain has been suggested as a potential therapeutic strategy for AD. We developed a screening platform, ATRIVIEW®, for molecules that activate neuronal differentiation of adult mouse NSCs. The most potent hit from an FDA-approved drug library was SNR1611 (trametinib), a selective MEK1/2 inhibitor. We found that trametinib increases the levels of P15INK4b and Neurog2, suggesting a mechanism by which MEK1/2 inhibition induces neuronal differentiation. Oral administration of trametinib increased adult neurogenesis in the dentate gyrus and subventricular zone of the 5XFAD AD mouse model. Surprisingly, we also found that trametinib enhanced adult neurogenesis in the cortex. Consequently, trametinib rescued AD pathologies such as neuronal loss and cognitive impairment in 5XFAD mice. Finally, trametinib induced neurogenic differentiation of NSCs derived from AD patient iPSCs, which suggests its potential therapeutic application. Altogether, we suggest that restoration of endogenous adult neurogenesis by trametinib may be a promising therapeutic approach to AD.

      • KCI등재

        Establishment of normal reference intervals in serum biochemical parameters of domestic sows in Korea

        Dongyub Kim,Hwan-Deuk Kim,Youngmin Son,Sungho Kim,Min Jang,Seul-Gi Bae,Sung-Ho Yun,Seung-Joon Kim,Won-Jae Lee 한국동물생명공학회(구 한국동물번식학회) 2021 Journal of Animal Reproduction and Biotechnology Vol.36 No.4

        Because sows are industrially vital for swine production, monitoring for their health or disorder status is important to ensure high reproductive performance. Especially, ambient temperature changes in different season, especially during summer, are directly influenced to the reproductive performance of sows. Although the serum biochemical parameters are widely applied in the veterinary medicine with wide ranges for the physiological process, the values are also influenced by several factors such as age, breed, gender, and stress. In addition, domestic sows in Koreaspecific reference interval (RI) for serum biochemistry has not been established yet. Therefore, the present study was aimed to evaluate seasonal variation of RIs in the serum biochemistry in domestic sows in Korea at different seasons and to establish normal RIs using a RI finding program (Reference Value Advisor). Significant difference (p < 0.05) on the different seasons were identified in several serum biochemical parameters including BUN, CRE, GGT, GLU, ALB, TP, LDH and Na in sows. Therefore, we further established RIs, specific in domestic sows in Korea regardless of season. The established RIs based on the serum biochemical values provide a baseline for interpreting biochemical results in the domestic sows in Korea, regardless of seasonal effect. It may contribute to develop a strategy for better reproductive performance by improving breeding management practice and evaluating health of pig herds, which facilitate to avert the economic loss in summer infertility in sows.

      • KCI등재

        어린이집 원장의 보육교사 실습지도에 대한 인식과 개선방안 연구

        홍성호(Sungho Hong),강혜원(HyeWon Kang),김애숙(Aesook Kim),김유진(Yoojin Kim),김정숙(Jeongsook Kim),김태정(Taejung Kim),양보경(Bokyung Yang),오혜정(Hyejeong Oh),유기미(Gimi Yoo),윤은미(Eunmi Yoon),이선미(Sunmi Lee),이재미(Jaemi Lee),최선숙 학습자중심교과교육학회 2021 학습자중심교과교육연구 Vol.21 No.1

        본 연구는 어린이집 원장의 보육실습지도에 대한 인식과 개선방안을 알아보기 위해 2018년부터 2020년까지 보육실습생을 지도한 23명의 원장을 대상으로 면담유형을 도출하고 8명과 심층 면담을 진행하고 분석하였다. 이를 위해 도출된 항목은 예비보육교사에게 요구되는 영역, 보육실습 지침서 관계영역, 보육실습지도 의미영역, 보육실습 개선방안 영역으로 분류되었고 면담준거를 설정하여 반구조화 된 면담지를 개발하였고 4명씩 2그룹으로 나누어 심층면담을 진행하였다. 수집된 자료는 전사하여 자료의 해석, 코딩, 분류 등의 유기적 데이터 분석을 하였고 파랑새 2.0를 이용하였다. 연구결과 첫째, 예비보육교사에게 요구되는 영역에서 열정적 태도, 긍정적 자아개념, 인·적성을 갖춘 전문적인 교사 자질의 필요성을 인식하였다. 둘째, 보육실습 지침서 관계영역에서 개정교육과정에 맞는 수정, 보완 후 현장적용의 필요성과 서류와 일지의 일원화, 간소화의 필요성을 인식하였다. 셋째, 보육실습지도 의미영역에서 짧은 교육과정을 이수한 보육실습생의 전문적 자질 부족과 실습지도의 어려움으로 자격과정을 3년제 이상으로 확대하여야 함과 복수전공 자격취득제도 철회의 필요성을 인식하였다. 넷째, 보육실습 개선방안 영역에서는 인·적성 검사도입, 예비보육교사 자격 강화, 보육실습 기준안 마련, 면접시스템 도입, 보육실습 지도교사의 처우개선, 보육실습 지침서의 활용도 있는 개정의 지원이라는 정책적 시사점을 제시하였다. In this study, in order to find out how the daycare center directors perceived childcare practice guidance and how to improve it, interview types were derived from 23 directors who taught childcare interns from 2018 to 2020, and conducted and analyzed in-depth interviews with 8 people. The items derived for this were classified into areas required for pre-service nursery teachers, related areas for childcare practice guidelines, meaning areas for childcare practice guidance, and areas for improvement measures for childcare practice, and developed semi-structured interview sheets by setting the interview criteria. The in-depth interview was divided into two. The collected data was transcribed to analyze organic data such as data interpretation, coding, and classification, and Bluebird 2.0 was used. As a result of the study, first, the need for professional teacher qualities with passionate attitude, positive self-concept, and personality and aptitude was recognized in the areas required for pre-service nursery teachers. Second, the need for field application after revision and supplementation in accordance with the revised curriculum in the related areas of the childcare practice guideline and the necessity of unifying and simplifying documents and journals were recognized. Third, in the field of childcare practice guidance, the need to withdraw the dual-major qualification acquisition system was recognized because of the lack of professional qualities and difficulty in training the childcare trainees who completed the short curriculum. Fourth, in the area of improvement measures for childcare practice, policy implications such as introduction of personality and aptitude tests, reinforcement of pre-service childcare teacher qualifications, preparation of childcare practice standards, introduction of an interview system, improvement of the treatment of childcare practice supervisors, and the use of childcare practice guidelines are supported. Presented.

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