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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>
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.
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>
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.
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>
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>
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.
Lung Transplantation in Six Patients with Idiopathic Pulmonary Artery Hypertension
( Hyeonhwa Kim ),( Dongkwan Kim ),( Sehoon Choi ),( Geundong Lee ),( Dongkyu Oh ),( Hocheol Kim ),( Jaeseung Lee ),( Sungho Jung ),( Pilje Kang ),( Won Kim ),( Seungil Park ),( Sangbum Hong ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0
Idiopathic pulmonary artery hypertension (IPAH) is an incurable and invariably fatal disease. Lung transplantation is a useful therapeutic option in patients who are unresponsive to medical treatment; however, lung transplantation performed for pulmonary hypertension is associated with significantly high perioperative mortality rates. We report a case series of six patients who underwent lung transplantation for IPAH between October 2008 and June 2021. Patients’ median age was 28.5 years, and the study included 5 of 6 women (83%). Pre-transplantation hemodynamic parameters showed mean right atrial pressure of 12.0±7.1 mmHg and mean pulmonary artery pressure of 62.2±29.5 mmHg. Two of six patients received extracorporeal membrane oxygenation (ECMO) therapy as a bridge to transplantation over 14 and 17 days, and four patients underwent elective transplantation. Two patients required prolonged postoperative venoarterial (V-A) ECMO support. Grade 3 primary graft dysfunction occurred in one patient; however, the clinical course improved following prolonged V-A ECMO therapy. Five patients (83.3%) required intervention for postoperative bleeding control; one of these patients died of uncontrolled bleeding concomitant with disseminated intravascular coagulation, on the 14th postoperative day, and we observed no other perioperative deaths. One patient died of carbapenem-resistant Acinetobacter baumannii bacteremia, a year postoperatively. The 1-month, 6-month, and 1-year survival rates were 83.3%, 83.3%, and 66.7%, respectively. In view of the poor prognosis of IPAH, lung transplantation (1-year mortality rates <40%) merits consideration as a useful therapeutic option in this patient population. However, postoperative bleeding tends to occur in most patients; therefore, close monitoring is important during post-transplantation management.