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Regulation of the Hippo signaling pathway by ubiquitin modification

  • Kim, Youngeun;Jho, Eek-hoon
    • BMB Reports
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    • v.51 no.3
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    • pp.143-150
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    • 2018
  • The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. ${\beta}-TrCP$ is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway.

Optimization of Dual Layer Phoswich Detector for Small Animal PET using Monte Carlo Simulation

  • Y.H. Chung;Park, Y.;G. Cho;Y.S. Choe;Lee, K.H.;Kim, S.E.;Kim, B.T.
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2003.09a
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    • pp.44-44
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    • 2003
  • As a basic measurement tool in the areas of animal models of human disease, gene expression and therapy, and drug discovery and development, small animal PET imaging is being used increasingly. An ideal small animal PET should have high sensitivity and high and uniform resolution across the field of view to achieve high image quality. However, the combination of long narrow pixellated crystal array and small ring diameter of small animal PET leads to the degradation of spatial resolution for the source located at off center. This degradation of resolution can be improved by determining the depth of interaction (DOI) in the crystal and by taking into account the information in sorting the coincident events. Among a number of 001 identification schemes, dual layer phsowich detector has been widely investigated by many research groups due to its practicability and effectiveness on extracting DOI information. However, the effects of each crystal length composing dual layer phoswich detector on DOI measurements and image qualities were not fully characterized. In order to minimize the DOI effect, the length of each layer of phoswich detector should be optimized. The aim of this study was to perform simulations using a simulation tool, GATE to design the optimum lengths of crystals composing a dual layer phoswich detector. The simulated small PET system employed LSO front layer LuYAP back layer phoswich detector modules and the module consisted of 8${\times}$8 arrays of dual layer crystals with 2 mm ${\times}$ 2 mm sensitive area coupled to a Hamamatsu R7600 00 M64 PSPMT. Sensitivities and variation of radial resolutions were simulated by varying the length of LSO front layer from 0 to 10 mm while the total length (LSO + LuYAP) was fixed to 20 mm for 10 cm diameter ring scanner. The radial resolution uniformity was markedly improved by using DOI information. There existed the optimal lengths of crystal layers to minimize the variation of radial resolutions. In 10 cm ring scanner configuration, the radial resolution was kept below 3.4 mm over 8 cm FOV while the sensitivity was higher than 7.4% for LSO 5 mm : LuYAP 15 mm phoswich detector. In this study, the optimal length of dual layer phoswich detector was derived to achieve high and uniform radial resolution.

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Music Generation from Motion of Fish based on Running Averaging Background Subtraction Method (이동평균 배경제거 기반의 물고기 모션 검출을 통한 음악 생성)

  • Yap, Wah-Seng;Cho, Dong-Chan;Kim, Whoi-Yul
    • Proceedings of the Korea Contents Association Conference
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    • 2011.05a
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    • pp.415-416
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    • 2011
  • This paper describes about a technique of generating music from the natural motion of fish which are detected via the running averaging background subtraction method. The motion of the fish will create musical notes on a background frame which will be analyzed and played by a music playing module that is proposed in this paper called "PhysicX". This module is also capable of interacting with the fishes. in the tank.

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A Novel Optimization-Based Approach for Minimum Power Multicast in Wireless Networks

  • Yen, Hong-Hsu;Lee, Steven S.W.;Yap, Florence G.H.
    • Journal of Communications and Networks
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    • v.13 no.1
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    • pp.26-31
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    • 2011
  • In this paper, we formulate the minimum power multicast problem in wireless networks as a mixed integer linear programming problem and then propose a Lagrangean relaxation based algorithm to solve this problem. By leveraging on the information from the Lagrangean multiplier, we could construct more power efficient routing paths. Numerical results demonstrate that the proposed approach outperforms the existing approaches for broadcast, multicast, and unicast communications.

A study on the regional expression through pavilion architecture - focused on the YAP pavilion (파빌리온 건축을 통해 본 지역성 표현특성에 대한 연구 - 젊은 건축가 프로그램 파빌리온을 중심으로)

  • Seo, Kyuduhk
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.2
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    • pp.42-49
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    • 2018
  • In this study, "Young Architects Program" pavilion architecture, where many formal, material, structural challenges were examined, was selected for an analysis of the regional expression of various culture in five countries in different continents. For comparative analysis, five criteria of evaluation, symbolic, tectonic, contextual, tactile, environmental, were set through an analysis of previous studies. Through these five criteria, the methods of regional expression of architectural concepts in five different countries were compared to indicate the characteristics of the different culture in same theme and type of pavilion architecture.

Hippo Signal Transduction Mechanisms in T Cell Immunity

  • Antoine Bouchard;Mariko Witalis;Jinsam Chang;Vincent Panneton;Joanna Li;Yasser Bouklouch;Woong-Kyung Suh
    • IMMUNE NETWORK
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    • v.20 no.5
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    • pp.36.1-36.13
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    • 2020
  • Hippo signaling pathways are evolutionarily conserved signal transduction mechanisms mainly involved in organ size control, tissue regeneration, and tumor suppression. However, in mammals, the primary role of Hippo signaling seems to be regulation of immunity. As such, humans with null mutations in STK4 (mammalian homologue of Drosophila Hippo; also known as MST1) suffer from recurrent infections and autoimmune symptoms. Although dysregulated T cell homeostasis and functions have been identified in MST1-deficient human patients and mouse models, detailed cellular and molecular bases of the immune dysfunction remain to be elucidated. Although the canonical Hippo signaling pathway involves transcriptional co-activator Yes-associated protein (YAP) or transcriptional coactivator with PDZ motif (TAZ), the major Hippo downstream signaling pathways in T cells are YAP/TAZ-independent and they widely differ between T cell subsets. Here we will review Hippo signaling mechanisms in T cell immunity and describe their implications for immune defects found in MST1-deficient patients and animals. Further, we propose that mutual inhibition of Mst and Akt kinases and their opposing roles on the stability and function of forkhead box O and β-catenin may explain various immune defects discovered in mutant mice lacking Hippo signaling components. Understanding these diverse Hippo signaling pathways and their interplay with other evolutionarily-conserved signaling components in T cells may uncover molecular targets relevant to vaccination, autoimmune diseases, and cancer immunotherapies.

Marine Mollusk Fauna of Kosrae Island, Federated States of Micronesia

  • Lee, Sang-Hwa;Park, Joong-Ki
    • The Korean Journal of Malacology
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    • v.29 no.4
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    • pp.343-376
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    • 2013
  • The Federated States of Micronesia consists of four states of Yap, Chuuk, Pohnpei and Kosrae, which are located in the West Pacific Ocean. In order to investigate molluscan fauna of Kosrae Island, field survey was made twice from 21st to 30th of January, 2011 and from 6th to 17th of January, 2012 for four localities including 10 intertidal and 14 subtidal zones of Kosrae Island. The mollusk samples collected were identified based on their morphological characteristics, comprising a total of 120 species from 30 families through this survey. In this study, we provided species list and illustrations for 120 species identified, and combined these with the previous record, resulting in a total of 208 species from 47 families in Kosrae Island.

Hippo Signaling Circuit and Divergent Tissue Growth in Mammalian Eye

  • Moon, Kyeong Hwan;Kim, Jin Woo
    • Molecules and Cells
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    • v.41 no.4
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    • pp.257-263
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    • 2018
  • Vertebrate organ development is accompanied by demarcation of tissue compartments, which grow coordinately with their neighbors. Hence, perturbing the coordinative growth of neighboring tissue compartments frequently results in organ malformation. The growth of tissue compartments is regulated by multiple intercellular and intracellular signaling pathways, including the Hippo signaling pathway that limits the growth of various organs. In the optic neuroepithelial continuum, which is partitioned into the retina, retinal pigment epithelium (RPE) and ciliary margin (CM) during eye development, the Hippo signaling activity operates differentially, as it does in many tissues. In this review, we summarize recent studies that have explored the relationship between the Hippo signaling pathway and growth of optic neuroepithelial compartments. We will focus particularly on the roles of a tumor suppressor, neurofibromin 2 (NF2), whose expression is not only dependent on compartment-specific transcription factors, but is also subject to regulation by a Hippo-Yap feedback signaling circuit.

Emerging functions for ANKHD1 in cancer-related signaling pathways and cellular processes

  • de Almeida, Bruna Oliveira;Machado-Neto, Joao Agostinho
    • BMB Reports
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    • v.53 no.8
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    • pp.413-418
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    • 2020
  • ANKHD1 (ankyrin repeat and KH domain containing 1) is a large protein characterized by the presence of multiple ankyrin repeats and a K-homology domain. Ankyrin repeat domains consist of widely existing protein motifs in nature, they mediate protein-protein interactions and regulate fundamental biological processes, while the KH domain binds to RNA or ssDNA and is associated with transcriptional and translational regulation. In recent years, studies containing relevant information on ANKHD1 in cancer biology and its clinical relevance, as well as the increasing complexity of signaling networks in which this protein acts, have been reported. Among the signaling pathways of interest in oncology regulated by ANKHD1 are Hippo signaling, JAK/STAT, and STMN1. The scope of the present review is to survey the current knowledge and highlight future perspectives for ANKHD1 in the malignant phenotype of cancer cells, exploring biological, functional, and clinical reports of this protein in cancer.