• Title/Summary/Keyword: HOMER

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Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice

  • Kang, Jung Yun;Kang, Namju;Shin, Dong Min;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.45 no.3
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    • pp.126-133
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    • 2020
  • Homer proteins are scaffold proteins that regulate calcium (Ca2+) signaling by modulating the activity of multiple Ca2+ signaling proteins. In our previous report, Homer2 and Homer3 regulated NFATc1 function through its interaction with calcineurin, which then acted to regulate receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone metabolism. However, to date, the role of Homers in osteoclastogenesis remains unknown. In this study, we investigated the roles of Homer2 and Homer3 in aging-dependent bone remodeling. Deletion of Homer2/Homer3 (Homer2/3 DKO) markedly decreased the bone density of the femur. The decrease in bone density was not seen in mice with Homer2 (Homer2-/-) and Homer3 (Homer3-/-) deletion. Moreover, RANKL treatment of bone marrow-derived monocytes/macrophages in Homer2/3 DKO mice significantly increased the formation of multinucleated cells and resorption areas. Finally, Homer2/3 DKO mice decreased bone density in an aging-dependent manner. These findings suggest a novel potent mode of bone homeostasis regulation through osteoclasts differentiation during aging by Homer proteins, specifically Homer2 and Homer3.

Growth and Differentiation Effects of Homer3 on a Leukemia Cell Line

  • Li, Zheng;Qiu, Hui-Ying;Jiao, Yang;Cen, Jian-Nong;Fu, Chun-Mei;Hu, Shao-Yan;Zhu, Ming-Qing;Wu, De-Pei;Qi, Xiao-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2525-2528
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    • 2013
  • The Homer protein family, also known as the family of cytoplasmic scaffolding proteins, which include three subtypes (Homer1, Homer2, Homer3). Homer3 can regulate transcription and play a very important role in the differentiation and development for some tissues (e.g. muscle and nervous systems). The current studies showed that Homer3 abnormal expression changes in acute myeloid leukemia (AML). Forced expression of Homer3 in transfected K562 cells inhibited proliferation, influenced the cell cycle profile, affected apoptosis induced by $As_2O_3$ through inhibition of Bcl2 expression, and also promoted cell differentiation induced by 12-O-tetra decanoylphorbol-acetate (TPA). These results showed that Homer3 is a novel gene which plays a certain role in the occurrence and development of AML.

Regulation of the expression and function of TRPCs and Orai1 by Homer2 in mouse pancreatic acinar cells

  • Kang, Jung Yun;Kang, Namju;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.46 no.3
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    • pp.134-139
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    • 2021
  • Under physiological conditions, calcium (Ca2+) regulates essential functions of polarized secretory cells by the stimulation of specific Ca2+ signaling mechanisms, such as increases in intracellular Ca2+ concentration ([Ca2+]i) via the store-operated Ca2+ entry (SOCE) and the receptor-operated Ca2+ entry (ROCE). Homer proteins are scaffold proteins that interact with G protein-coupled receptors, inositol 1,4,5-triphosphate (IP3) receptors, Orai1-stromal interaction molecule 1, and transient receptor potential canonical (TRPC) channels. However, their role in the Ca2+ signaling in exocrine cells remains unknown. In this study, we investigated the role of Homer2 in the Ca2+ signaling and regulatory channels to mediate SOCE and ROCE in pancreatic acinar cells. Deletion of Homer2 (Homer2-/-) markedly increased the expression of TRPC3, TRPC6, and Orai1 in pancreatic acinar cells, whereas these expressions showed no difference in whole brains of wild-type and Homer2-/- mice. Furthermore, the response of Ca2+ entry by carbachol also showed significant changes to the patterns regulated by specific blockers of SOCE and ROCE in pancreatic acinar cells of Homer2-/- mice. Thus, these results suggest that Homer2 plays a critical role in the regulatory action of the [Ca2+]i via SOCE and ROCE in mouse pancreatic acinar cells.

Homer2 regulates amylase secretion via physiological calcium oscillations in mouse parotid gland acinar cells

  • Kang, Namju;Kang, Jung Yun;Shin, Dong Min;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.45 no.2
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    • pp.58-63
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    • 2020
  • The salivary glands secrete saliva, which plays a role in the maintenance of a healthy oral environment. Under physiological conditions, saliva secretion within the acinar cells of the gland is regulated by stimulation of specific calcium (Ca2+) signaling mechanisms such as increases in the intracellular Ca2+ concentration ([Ca2+]i) via storeoperated Ca2+ entry, which involves components such as Orai1, transient receptor potential (TRP) canonical 1, stromal interaction molecules, and inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs). Homer proteins are scaffold proteins that bind to G protein-coupled receptors, IP3Rs, ryanodine receptors, and TRP channels. However, their exact role in Ca2+ signaling in the salivary glands remains unknown. In the present study, we investigated the role of Homer2 in Ca2+ signaling and saliva secretion in parotid gland acinar cells under physiological conditions. Deletion of Homer2 (Homer2-/-) markedly decreased the amplitude of [Ca2+]i oscillations via the stimulation of carbachol, which is physiologically concentrated in parotid acinar cells, whereas the frequency of [Ca2+]i oscillations showed no difference between wild-type and Homer2-/- mice. Homer2-/- mice also showed a significant decrease in amylase release by carbachol in the parotid gland in a dose-dependent manner. These results suggest that Homer2 plays a critical role in maintaining [Ca2+]i concentration and secretion of saliva in mouse parotid gland acinar cells.

Regulatory mechanisms of the store-operated Ca2+ entry through Orai1 and STIM1 by an adaptor protein in non-excitable cells

  • Kang, Jung Yun;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.47 no.3
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    • pp.33-40
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    • 2022
  • Store-operated Ca2+ entry (SOCE) represents one of the major Ca2+ entry routes in non-excitable cells. It is involved in a variety of fundamental biological processes and the maintenance of Ca2+ homeostasis. The Ca2+ release-activated Ca2+ (CRAC) channel consists of stromal interaction molecule and Orai; however, the role and action of Homer proteins as an adaptor protein to SOCE-mediated Ca2+ signaling through the activation of CRAC channels in non-excitable cells still remain unknown. In the present study, we investigated the role of Homer2 in the process of Ca2+ signaling induced by the interaction between CRACs and Homer2 proteins in non-excitable cells. The response to Ca2+ entry by thapsigargin-mediated Ca2+ store depletion remarkably decreased in pancreatic acinar cells of Homer2-/- mice, as compared to wild-type cells. It also showed critical differences in regulated patterns by the specific blockers of SOCE in pancreatic acinar cells of Homer2-/- mice. The response to Ca2+ entry by the depletion in Ca2+ store markedly increased in the cellular overexpression of Orai1 and STIM1 as compared to the overexpression of Homer2 in cells; however, this response was remarkably inhibited by the overexpression of Orai1, STIM1, and Homer2. These results suggest that Homer2 has a critical role in the regulatory action of SOCE activity and the interactions between CRAC channels.

Identification of Homer1 as a Potential Prognostic Marker for Intrahepatic Cholangiocarcinoma

  • Wu, San-Yun;Yu, Ming-Xia;Li, Xiao-Gai;Xu, Shu-Fang;Shen, Ji;Sun, Zhen;Zhou, Xin;Chen, Xing-Zhen;Tu, Jian-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3299-3304
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    • 2014
  • Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.

Energy Power Source Design for Island Using HOMER Program (도서지역에서 HOMER프로그램을 이용한 발전원의 적정규모 산정)

  • Park, Jonghoon;Nguyen, Tuan Anh;Choi, Jaeho
    • Proceedings of the KIPE Conference
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    • 2016.11a
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    • pp.200-201
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    • 2016
  • 최근 계통연계가 도서산간지역의 전력문제 해결방안으로 마이크로그리드가 해법으로 제시되고 있다. 신재생에너지 및 디젤발전으로 구성되는 마이크로그리드는 신재생자원의 간헐적인 출력 때문에 적정규모를 선정하는데 어려움이 있다. 본 논문에서는 신재생 에너지의 간헐적인 출력을 고려하여 HOMER프로그램을 이용하여 적정 규모를 선정하고 감도 분석을 통하여 최적점을 설계하고 부하를 변경하였을 때 적절한 규모를 산정해본다.

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Optimization of Residential Photovoltaic-Fuel Cell Hybrid System Using HOMER(R) (HOMER를 이용한 가정용 태양광-연료전지 하이브리드시스템의 운전 최적화)

  • Park, Se-Joon;Li, Ying;Choi, Young-Sung;Lee, Kyung-Sup
    • The Transactions of the Korean Institute of Electrical Engineers P
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    • v.59 no.1
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    • pp.129-133
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    • 2010
  • A hybrid system which is combined several complementary new and renewable power sources, such as photovoltaic, fuel-cell, and wind generator, etc., has been presented in various approaches. For instance, a photovoltaic cannot always generate stable output power with ever-changing weather condition, so it might be co-generated with a wind generator, diesel generator, and some other sources. In this paper, a residential PV-FC hybrid system is suggested as a distribution power source, and its operation is optimized by HOMER$^{(R)}$. As a result, it is the most economic that 5[kW] PV, 1[kW] FC, 4 batteries, 2[kW] electrolyzer, 0.5[kg] $H_2$ tank, 3[kW] converter are applied to the hybrid system.

An Economic feasibility Analysis for New and Renewable Hybrid Energy System by using HOMER (HOMER를 이용한 신재생복합전력시스템의 경제성 분석 - Off-grid 도서지역을 중심으로 -)

  • Baek, Minho;Cho, Seulgi;Kim, Suduk
    • 한국신재생에너지학회:학술대회논문집
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    • 2011.05a
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    • pp.75.2-75.2
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    • 2011
  • 국내 유인도서의 상당수는 전력의 대부분을 디젤발전으로 생산한다. 향후 발전설비의 교체 혹은 증설이 있을 경우 신재생에너지원 설비의 보급 여지가 있다. 이에 본 연구는 울릉도에 화력발전 설비만을 증설했을 경우와 이를 신재생에너지복합시스템 설비로 대체했을 때의 경제적 타당성을 비교분석한다. 우리는 복합발전 시스템을 풍력터빈, PV, 소수력발전 등의 신재생에너지 설비, Batteries, Converter와 같은 보조전원, 저장 및 back up을 위한 flywheel과 Diesel generator등으로 구성했다. 분석에 사용한 HOMER(Hybrid Optimization for Energy Renewable)는 신재생에너지복합 발전시스템 분석에 사용되며 결과를 NPC(Net Present Cost)의 오름차순으로 제시하여 발전설비구성의 조합들 중 최적의 시나리오를 보여준다. 분석결과 울릉도의 경우 신재생에너지복합 발전의 보급이 잠재적으로 가능할 것으로 보인다. 또한 계통운영의 기술적인 측면을 감안할 경우 정밀한 분석이 가능할 것이다. 따라서 본 연구는 계통운영과 경제성분석 연구의 연계를 위한 사전연구로써 그 의미를 갖는다.

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Optimization of Stand-Alone Hybrid Power Systems Using HOMER Program (HOMER 프로그램을 이용한 독립형 하이브리드 발전시스템 최적화)

  • Yang, Su-Hyung;Boo, Chang-Jin;Kim, Ho-Chan
    • Journal of the Korean Solar Energy Society
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    • v.32 no.2
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    • pp.11-18
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    • 2012
  • Diesel fuel is expensive because transportation to remote areas adds extra cost, and it causes air pollution by engine exhaust. Providing a feasible economical and environmental solution to diesel generators is important. A hybrid system of renewable plants and diesel generators can benefit islands or other isolated communities and increase fuel savings. Renewable energy is, however, a natural source that produces a fluctuating power output. In this paper, hybrid power system of the marado lighthouse is proposed to supply stable power in the stand-alone hybrid power system. The proposed hybrid power system consists of the diesel generator, wind turbine, photovoltaic, fuel cell, and battery bank. To decrease the carbon emissions and find the optimization, the cost analysis of hybrid system is simulated using HOMER program and the optimized hybrid power system is designed.