• Title/Summary/Keyword: yap

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Inhibition of the interaction between Hippo/YAP and Akt signaling with ursolic acid and 3'3-diindolylmethane suppresses esophageal cancer tumorigenesis

  • Ruo Yu Meng;Cong Shan Li;Dan Hu;Soon-Gu Kwon;Hua Jin;Ok Hee Chai;Ju-Seog Lee;Soo Mi Kim
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.5
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    • pp.493-511
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    • 2023
  • Hippo/YAP signaling hinders cancer progression. Inactivation of this pathway contributes to the development of esophageal cancer by activation of Akt. However, the possible interaction between Akt and Hippo/YAP pathways in esophageal cancer progression is unclear. In this study, we found that ursolic acid (UA) plus 3'3-diindolylmethane (DIM) efficiently suppressed the oncogenic Akt/Gsk-3β signaling pathway while activating the Hippo tumor suppressor pathway in esophageal cancer cells. Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells. Silencing YAP under UA plus DIM conditions significantly increased the activation of the tumor suppressor PTEN in esophageal cancer cells, while decreasing p-Akt activation, indicating that the Akt signaling pathway could be down-regulated in esophageal cancer cells by targeting PTEN. Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.

Isolation of High Yielding Alkaline Protease Mutants of Vibrio metschnikovii Strain RH530 and Detergency Properties of Enzyme

  • Chung, So-Sun;Shin, Yong-Uk;Kim, Hee-Jin;Jin, Ghee-Hong;Rho, Hyune-Mo;Lee, Hyune-Hwan
    • Journal of Microbiology and Biotechnology
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    • v.10 no.3
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    • pp.349-354
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    • 2000
  • Abstract A facultative alkalophilic gram-negative Vibrio metschnikovii strain RH530, isolated from the wastewater, produced several alkaline proteases (VAP) including six alkaline serine proteases and a metalloprotease. From this strain, high yielding YAP mutants were isolated by NTG treatment. The isolated mutant KS1 showed nine times more activity than the wild-type after optimization of the culture media. The production was regulated by catabolite repression when glucose was added to the medium. The effects of several organic nitrogen sources on the production of the YAP were investigated to avoid catabolite repression. The combination of 4% wheat gluten meal (WGM), 1.5% cotton seed flour (eSF), and 5% soybean meal (SBM) resulted in the best production when supplemented with 1% NaCl. The YAP showed a resistance to surfactants such as $sodium-{\alpha}-olefin$ sulfonate (AOS), polyoxy ethylene oxide (POE), and sodium dodecyl sulfate (SDS), yet not to linear alkylbenzene sulfonate (LAS). However, the activity of the YAP was restored completely when incubated with LAS in the presence of POE or $Na_2SO_4$. The YAP was stable in a liquid laundry detergent containing 6.6% SLES (sodium lauryl ether sulfate), 6.6% LAS, 19.8% POE, and stabilizing agents for more than two weeks at $40^{\circ}C$, but the stability was sharply decreased even after 1 day when incubated at $60^{\circ}C$. A washing performance test with the YAP exhibited it to be a good washing power by showing 51 % and 60% activity at $25^{\circ}C{\;}and{\;}40^{\circ}C$, respectively, thereby indicating that the YAP also has a good detergency at a low temperature. All the results suggest that the YAP produced from the mutant strain KSI has suitable properties for use in laundry detergents.rgents.

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Primary Study for dialogue based on Ordering Chatbot

  • Kim, Ji-Ho;Park, JongWon;Moon, Ji-Bum;Lee, Yulim;Yoon, Andy Kyung-yong
    • Journal of Multimedia Information System
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    • v.5 no.3
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    • pp.209-214
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    • 2018
  • Today is the era of artificial intelligence. With the development of artificial intelligence, machines have begun to impersonate various human characteristics today. Chatbot is one instance of this interactive artificial intelligence. Chatbot is a computer program that enables to conduct natural conversations with people. As mentioned above, Chatbot conducted conversations in text, but Chatbot, in this study evolves to perform commands based on speech-recognition. In order for Chatbot to perfectly emulate a human dialogue, it is necessary to analyze the sentence correctly and extract appropriate response. To accomplish this, the sentence is classified into three types: objects, actions, and preferences. This study shows how objects is analyzed and processed, and also demonstrates the possibility of evolving from an elementary model to an advanced intelligent system. By this study, it will be evaluated that speech-recognition based Chatbot have improved order-processing time efficiency compared to text based Chatbot. Once this study is done, speech-recognition based Chatbot have the potential to automate customer service and reduce human effort.

Saturated fatty acid-inducible miR-103-3p impairs the myogenic differentiation of progenitor cells by enhancing cell proliferation through Twinfilin-1/F-actin/YAP1 axis

  • Mai Thi Nguyen;Wan Lee
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.3
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    • pp.277-287
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    • 2023
  • Actin dynamics play an essential role in myogenesis through multiple mechanisms, such as mechanotransduction, cell proliferation, and myogenic differentiation. Twinfilin-1 (TWF1), an actin-depolymerizing protein, is known to be required for the myogenic differentiation of progenitor cells. However, the mechanisms by which they epigenetically regulate TWF1 by microRNAs under muscle wasting conditions related to obesity are almost unknown. Here, we investigated the role of miR-103-3p in TWF1 expression, actin filament modulation, proliferation, and myogenic differentiation of progenitor cells. Palmitic acid, the most abundant saturated fatty acid (SFA) in the diet, reduced TWF1 expression and impeded myogenic differentiation of C2C12 myoblasts, while elevating miR-103-3p levels in myoblasts. Interestingly, miR-103-3p inhibited TWF1 expression by directly targeting its 3'UTR. Furthermore, ectopic expression of miR-103-3p reduced the expression of myogenic factors, i.e., MyoD and MyoG, and subsequently impaired myoblast differentiation. We demonstrated that miR-103-3p induction increased filamentous actin (F-actin) and facilitated the nuclear translocation of Yes-associated protein 1 (YAP1), thereby stimulating cell cycle progression and cell proliferation. Hence, this study suggests that epigenetic suppression of TWF1 by SFA-inducible miR-103-3p impairs myogenesis by enhancing the cell proliferation triggered by F-actin/YAP1.

Tumor necrosis factor-inducible gene 6 interacts with CD44, which is involved in fate-change of hepatic stellate cells

  • Wang, Sihyung;Kim, Jieun;Lee, Chanbin;Jung, Youngmi
    • BMB Reports
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    • v.53 no.8
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    • pp.425-430
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    • 2020
  • Tumor necrosis factor-inducible gene 6 protein (TSG-6) is a cytokine secreted by mesenchymal stem cells (MSCs) and regulates MSC stemness. We previously reported that TSG-6 changes primary human hepatic stellate cells (pHSCs) into stem-like cells by activating yes-associated protein-1 (YAP-1). However, the molecular mechanism behind the reprogramming action of TSG-6 in pHSCs remains unknown. Cluster of differentiation 44 (CD44) is a transmembrane protein that has multiple functions depending on the ligand it is binding, and it is involved in various signaling pathways, including the Wnt/β-catenin pathway. Given that β-catenin influences stemness and acts downstream of CD44, we hypothesized that TSG-6 interacts with the CD44 receptor and stimulates β-catenin to activate YAP-1 during TSG-6-mediated transdifferentiation of HSCs. Immunoprecipitation assays showed the interaction of TSG-6 with CD44, and immunofluorescence staining analyses revealed the colocalization of TSG-6 and CD44 at the plasma membrane of TSG-6-treated pHSCs. In addition, TSG-6 treatment upregulated the inactive form of phosphorylated glycogen synthase kinase (GSK)-3β, which is a negative regulator of β-catenin, and promoted nuclear accumulation of active/nonphosphorylated β-catenin, eventually leading to the activation of YAP-1. However, CD44 suppression in pHSCs following CD44 siRNA treatment blocked the activation of β-catenin and YAP-1, which inhibited the transition of TSG-6-treated HSCs into stem-like cells. Therefore, these findings demonstrate that TSG-6 interacts with CD44 and activates β-catenin and YAP-1 during the conversion of TSG-6-treated pHSCs into stem-like cells, suggesting that this novel pathway is an effective therapeutic target for controlling liver disease.

The role of extracellular biophysical cues in modulating the Hippo-YAP pathway

  • Mo, Jung-Soon
    • BMB Reports
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    • v.50 no.2
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    • pp.71-78
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    • 2017
  • The Hippo signaling pathway plays an essential role in adult-tissue homeostasis and organ-size control. In Drosophila and vertebrates, it consists of a highly conserved kinase cascade, which involves MST and Lats that negatively regulate the activity of the downstream transcription coactivators, YAP and TAZ. By interacting with TEADs and other transcription factors, they mediate both proliferative and antiapoptotic gene expression and thus regulate tissue repair and regeneration. Dysregulation or mutation of the Hippo pathway is linked to tumorigenesis and cancer development. Recent studies have uncovered multiple upstream inputs, including cell density, mechanical stress, G-protein-coupled receptor (GPCR) signaling, and nutrients, that modulate Hippo pathway activity. This review focuses on the role of the Hippo pathway as effector of these biophysical cues and its potential implications in tissue homeostasis and cancer.

A Study on Construction trend of Pavilion with Viewpoint of the 'Lightness' - In Case Studies on the winner project of Young Architecture Program(YAP) in MoMA PS1 - (파빌리온의 경량화 구축 특성에 관한 연구 - MoMa P.S.1 젊은 건축가 프로그램(YAP)의 우승작을 중심으로 -)

  • Kim, Jinjae;Jeon, You-Chang;Kim, Sung-Wook
    • Journal of the Korean Institute of Educational Facilities
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    • v.26 no.6
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    • pp.51-58
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    • 2019
  • This study embody the investigation of the winner projects of Young Architecture Program(YAP) taken place annually at front yard of MoMA PS1 since 1998. Every installation of project is experimental exhibition that have ambiguous border in the area between lightness and architecture. Thus the design have less limits as architectural space and talents can express the innovative idea strong. This paper aims to probe annual significant key words by analyzing the contemporary representative space types, materials, fabrication methods and innovative ideas, and to identify the changes of important concept of lightness and recent trend in architect design concept.

A Study on the Habitat of Gidra Community in Papua New Guinea with Satellite Remote Sensing

  • Pahari, Krishna;Ohtsuka, Ryutaro
    • Proceedings of the KSRS Conference
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    • 2003.11a
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    • pp.1159-1161
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    • 2003
  • Gidra speaking people living in Wonnie area of western province in Papua New Guinea are traditionally dependent on hunting and gathering. Sago is the main staple food and the vegetation consists of rain forest (Bua) and trees with savannah grass (Yap). The population density is very low and the people are very little affected by modernization. This study is an attempt to look at the people-resource interaction in the area for the past thirty years based on aerial photographs and various satellite data. The study showed the trends of yap versus bua distribution as well as the location of garden and Sago grove areas, which is important for studying the livelihood of the people.

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Influences of Pump Spot Radius and Depth of Focus on the Thermal Effect of Tm:YAP Crystal

  • Zhang, Hongliang;Wen, Ya;Zhang, Lin;Fan, Zhen;Liu, Jinge;Wu, Chunting
    • Current Optics and Photonics
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    • v.3 no.5
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    • pp.458-465
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    • 2019
  • The thermal effect and the light output of a laser crystal under different pumping depths were reported., Based on the thermal model of a single-ended pumped Tm:YAP crystal, the thermal stress coupled model used Comsol to theoretically calculate the effect of changing the pump spot size and pump depth on crystal heat distribution and stress distribution. The experimental results showed that the laser output power first increased and then decreased with increasing pump spot size. As the depth of focus increased, the laser output power first increased and then decreased. The experimental results were consistent with the theoretical simulation results. The theory of pump spot radius and depth of focus in this paper provided an effective simulation method for mitigating thermal effects, and provided theoretical supports for laser crystals to obtain higher laser output power.

A novel role of Hippo-Yap/TAZ signaling pathway in lymphatic vascular development

  • Cha, Boksik;Moon, Sungjin;Kim, Wantae
    • BMB Reports
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    • v.54 no.6
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    • pp.285-294
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    • 2021
  • The lymphatic vasculature plays important role in regulating fluid homeostasis, intestinal lipid absorption, and immune surveillance in humans. Malfunction of lymphatic vasculature leads to several human diseases. Understanding the fundamental mechanism in lymphatic vascular development not only expand our knowledge, but also provide a new therapeutic insight. Recently, Hippo-YAP/TAZ signaling pathway, a key mechanism of organ size and tissue homeostasis, has emerged as a critical player that regulate lymphatic specification, sprouting, and maturation. In this review, we discuss the mechanistic regulation and pathophysiological significant of Hippo pathway in lymphatic vascular development.