• Title/Summary/Keyword: functional role

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FUN14 Domain-Containing Protein 1 Is Involved in Amyloid Beta Peptide-Induced Mitochondrial Dysfunction and Cell Injury in HT-22 Neuronal Cells (HT-22 신경세포에서 아밀로이드 베타 펩티드에 의한 미토콘드리아와 세포 손상 기전에서 FUN14 도메인 함유 단백 1의 역할)

  • Jae Hoon Kang;Jae Suk Woo
    • Journal of Life Science
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    • v.34 no.1
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    • pp.37-47
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    • 2024
  • FUN14 domain-containing protein 1 (FUNDC1), an outer mitochondrial membrane protein, contributes to removal of damaged mitochondria through mitophagy. In this study, to elucidate the role of the FUNDC1 in the amyloid beta peptide (Aβ)-induced neuropathy, changes in the degree of mitochondrial dysfunction and cell injury caused by Aβ treatment were examined in the HT-22 neuronal cells in which the FUNDC1 expression was transiently silenced or overexpressed. We found that Aβ treatment causes a time-dependent decrease of the FUNDC1 expression. In the Aβ-treated cells, there were a drop in MTT reduction ability, depletion of cellular ATP, disruption of mitochondrial membrane potential, stimulation of cellular ROS production, and increased mitochondrial Ca2+ load. Activation of caspase-3 and induction of apoptotic cell death were also observed. Transient silencing of the FUNDC1 expression by transfection with the FUNDC1 small interfering RNA per se caused mitochondrial dysfunction and apoptotic cell death like the effect of Aβ treatment. Conversely, in cells in which the FUNDC1 was transiently overexpressed by FUNDC1-Myc transfection, overexpression itself had no effect on the mitochondrial functional integrity and cell survival but showed a significant prevention effect against mitochondrial and cell injury caused by Aβ treatment. Overall, these results suggest that the FUNDC1 is importantly involved in the Aβ-induced mitochondrial dysfunction and cell injury in the HT-22 neuronal cells.

Bta-miR-365-3p-targeted FK506-binding protein 5 participates in the AMPK/mTOR signaling pathway in the regulation of preadipocyte differentiation in cattle

  • Mengdi Chen;Congcong Zhang;Zewen Wu;Siwei Guo;Wenfa Lv;Jixuan Song;Beibei Hao;Jinhui Bai;Xinxin Zhang;Hongyan Xu;Guangjun Xia
    • Animal Bioscience
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    • v.37 no.7
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    • pp.1156-1167
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    • 2024
  • Objective: MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods: We identified bta-miR-365-3p, which specifically targets the 3' untranslated region (3'UTR) of the FK506-binding protein 5 (FKBP5), and verified its mechanisms for regulating expression and involvement in adipogenesis. Results: In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-36 5-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by quantitative real-time polymerase chain reaction and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. Adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion: In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution

  • Ying Liu;Yan Chen;Xiao-Hua Li;Chong Cao;Hui-Xi Zhang;Cui Zhou;Yu Chen;Yun Gong;Jun-Xiao Yang;Liang Cheng;Xiang-Ding Chen;Hui Shen;Hong-Mei Xiao;Li-Jun Tan;Hong-Wen Deng
    • International Journal of Stem Cells
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    • v.16 no.3
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    • pp.342-355
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    • 2023
  • Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions: Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

Research on functional area-specific technologies application of future C4I system for efficient battlefield visualization (미래 지휘통제체계의 효율적 전장 가시화를 위한 기능 영역별 첨단기술 적용방안)

  • Sangjun Park;Jungho Kang;Yongjoon Lee;Jeewon Kim
    • Convergence Security Journal
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    • v.23 no.4
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    • pp.109-119
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    • 2023
  • C4I system is an integrated battlefield information system that automates the five elements of command, control, communications, computers, and information to efficiently manage the battlefield. C4I systems play an important role in collecting and analyzing enemy positions, situations, and operational results to ensure that all services have the same picture in real time and optimize command decisions and mission orders. However, the current C4I has limitations whenever a new weapon system is introduced, as it only provides battlefield visualization in a single area focusing on the battlefield situation for each military service. In a future battlefield that expands not only to land, sea, and air domains but also to cyber and space domains, improved command and control decisions will be possible if organic data from various weapon systems is gathered to quickly visualize the battlefield situation desired by the user. In this study, the visualization technology applicable to the future C4I system is divided into map area, situation map area, and display area. The technological implementation of this future C4I system is based on various data and communication means such as 5G networks, and is expected to enable hyper-connected battlefield visualization that utilizes a variety of high-quality information to enable realistic and efficient battlefield situation awareness.

Inhibitory effect of ethanol extract of Gryllus bimaculatus on platelet aggregation and glycoprotein IIb/IIIa activation (쌍별귀뚜라미 에탄올 추출물의 혈소판응집반응과 당단백질 IIb/IIIa 활성화 억제 효과)

  • Hyuk-Woo Kwon;Man Hee Rhee;Jung-Hae Shin
    • Journal of Applied Biological Chemistry
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    • v.66
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    • pp.236-243
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    • 2023
  • Platelets act a fundamental role in primary- and secondary-hemostasis, however, platelet activation may cause thrombosis simultaneously. Therefore, control of platelet aggregation is crucial in preventing thrombosis-mediated diseases. Recently, the development of insect materials is attracting attention. Among the highly nutritious functional food sources, insects such as two-spotted cricket (Gryllus bimaculatus). Gryllus bimaculatus (G. bimaculatus) contains high protein and unsaturated fatty acids and has been registered as a food material September 2015 by the Ministry of Food and Drug Safety of Korea. In this study, we examined whether G. bimaculatus extract (GBE) inhibits platelet aggregation, intracellular calcium mobilization, thromboxane A2 production and glycoprotein IIb/IIIa (integrin αIIb/β3) activation. We investigated whether GBE can regulate signaling molecules, such as 1, 4, 5-triphosphate receptor type I, extracellular signal-regulated kinase, cytosolic phospholipase A2, mitogen-activated protein kinases p38, vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt, glycogen synthase kinase-3α/β, and SYK. Taken together, GBE is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

A Study on a Effect of Product Design and a Primary factor of Qualify Competitiveness (제품 디자인의 파급효과와 품질경쟁력의 결정요인에 관한 연구)

  • Lim, Chae-Suk;Yoon, Jong-Young
    • Archives of design research
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    • v.18 no.4 s.62
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    • pp.95-104
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    • 2005
  • The purpose of this study is to estimate the determinants of product design and analyze the impacts of product design on quality competitiveness, product reliability, and consumer satisfaction in an attempt to provide a foundation for the theory of design management. For this empirical analysis, this study has derived the relevant measurement variables from a survey on 400 Korean manufacturing firms during the period of $August{\sim}October$ 2003. The empirical findings are summarized as follows: First, the determinants of product design are very significantly (at p<0.001) estimated to be the R&D capability, the level of R&D expenditure, the level of innovative activities(5S, TQM, 6Sigma, QC, etc.). This empirical result can support Pawar and Driva(1999)'s two principles by which the performance of product design and product development can be simultaneously evaluated in the context of CE(concurrent engineering) of NPD(newly product development) activities. Second, the hypothesis on the causality: product design${\rightarrow}$quality competitiveness${\rightarrow}$customer satisfaction${\rightarrow}$customer loyalty is very significantly (at p<0.001) accepted. This implies that product design positively affects consumer satisfaction, not directly but indirectly, by influencing quality competitiveness. This empirical result of this study can also support the studies of for example Flynn et al.(1994), Ahire et at.(1996), Afire and Dreyfus(2000) which conclude that design management is a significant determinant of product quality. The aforementioned empirical results are important in the following sense: the empirical result that quality competitiveness plays a bridging role between product design and consumer satisfaction can reconcile the traditional debate between QFD(quality function development) approach asserted by product developers and conjoint analysis maintained by marketers. The first empirical result is related to QFD approach whereas the second empirical result is related to conjoint analysis. At the same time, the empirical results of this study can support the rationale of design integration(DI) of Ettlie(1997), i.e., the coordination of the timing and substance of product development activities performed by the various disciplines and organizational functions of a product's life cycle. Finally, the policy implication (at the corporate level) from the empirical results is that successful design management(DM) requires not only the support of top management but also the removal of communication barriers, (i.e. the adoption of cross-functional teams) so that concurrent engineering(CE), the simultaneous development of product and process designs can assure product development speed, design quality, and market success.

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Functional Mapping of the Neural Basis for the Encoding and Retrieval of Human Episodic Memory Using ${H_2}^{15}O$ PET ({H_2}^{15}O$ PET을 이용한 정상인의 삽화기억 부호화 및 인출 중추 뇌기능지도화)

  • Lee, Jae-Sung;Nam, Hyun-Woo;Lee, Dong-Soo;Lee, Sang-Kun;Jang, Myoung-Jin;Ahn, Ji-Young;Park, Kwang-Suk;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.1
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    • pp.10-21
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    • 2000
  • Purpose: Episodic memory is described as an 'autobiographical' memory responsible for storing a record of the events in our lives. We performed functional brain activation study using ${H_2}^{15}O$ PET to reveal the neural basis of the encoding and the retrieval of episodic memory in human normal volunteers. Materials and Methods: Four repeated ${H_2}^{15}O$ PET scans with two reference and two activation tasks were performed on 6 normal volunteers to activate brain areas engaged in encoding and retrieval with verbal materials. Images from the same subject were spatially registered and normalized using linear and nonlinear transformation. Using the means and variances for every condition which were adjusted with analysis of covariance, t-statistic analysis were performed voxel-wise. Results: Encoding of episodic memory activated the opercular and triangular parts of left inferior frontal gyrus, right prefrontal cortex, medial frontal area, cingulate gyrus, posterior middle and inferior temporal gyri, and cerebellum, and both primary visual and visual association areas. Retrieval of episodic memory activated the triangular part of left inferior frontal gyrus and inferior temporal gyrus, right prefrontal cortex and medial temporal area, and both cerebellum and primary visual and visual association areas. The activations in the opercular part of left inferior frontal gyrus and the right prefrontal cortex meant the essential role of these areas in the encoding and retrieval of episodic memory. Conclusion: We could localize the neural basis of the encoding and retrieval of episodic memory using ${H_2}^{15}O$ PET, which was partly consistent with the hypothesis of hemispheric encoding/retrieval asymmetry.

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An investigation of the User Research Techniques in the User-Centered Design Framework - Focused on the on-line community services development for 13-18 Young Adults (사용자 중심 디자인 프레임워크에서 사용자 조사기법의 역할에 관한 연구 - 13-18 청소년용 온라인 커뮤니티 컨텐트 개발 프로젝트를 중심으로)

  • 이종호
    • Archives of design research
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    • v.17 no.2
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    • pp.77-86
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    • 2004
  • User-Centered Design Approach plays important role in dealing with usability issues for developing modern technology products. Yet it is still questionable whether the User-Centered approach is enough for the development of successful consumer contents since the User-Centered Design is originated from the software engineering field where meeting customers' functional requirement is the most critical aspect in developing a software. However, modern consumer market is already saturated and in order to meet ever increasing consumer requirements, the User-Centered Design approach needs to be expanded. As a way of incorporating the User-Centered Approach into the consumer product development, Jordan suggested the 'Pleasure-based Approach' in industrial design field, which usually generates multi-dimensional user requirements: 1)physical, 2)cognitive, 3)identity and 4) social. It is the current tendency that many portal and community service providers focus on fulfilling both functional and emotional needs for users when developing new items, contents and services. Previously fulfilling consumers' emotional needs solely depend on visual designer's graphical sense and capability. However, taking the customer-centered approach on withdrawing consumers' unknown needs is getting critical in the competitive market environment. This paper reviews different types of user research techniques and categorized into 6 ways based on Kano(1992)'s product quality model. Based on his theory, only performance factors, such as suability, can be identified through the user-centered design approach. The user-centered design approach has to be expanded to include factors include personality, sociability, pleasure, and so on. In order to identify performance as well as excellent factors through user research, a user-research framework was established and tested through the case study, which is ' the development of new online service for teens '. The results of the user research were summarized at the end of the paper and the pros and cons of each research techniques were analyzed.

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Synthesis and Antioxidative Activities of N,N'-Diferuloyl-putrescine (DFP) and Its Derivatives (N,N'-Diferuloyl-putrescine (DFP)과 그 유도체의 합성 및 항산화 활성)

  • Hwang, Jun Pil;Ha, Ji Hoon;Kim, Myung Kyoo;Park, Soo Nam
    • Applied Chemistry for Engineering
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    • v.26 no.1
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    • pp.29-34
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    • 2015
  • N,N'-Diferuloyl-putrescine (DFP) present in plants such as Sophora japonica has been reported to have skin depigmentative and antioxidative activities. In this study, DFP, usually presents in nature a very little amount and its derivative (DFP-D) were synthesized in a large quantity for the use as functional cosmetical materials. The antioxidative activities of synthesized DFP and DFP-D were evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, chemiluminescence assay, and cell protective effect induced by $^1O_2$, stress. DFP and DFP-D showed DPPH radical scavenging activities ($FSC_{50}$) at $61.25{\pm}2.25{\mu}M$ and $12.92{\pm}0.72{\mu}M$, respectively. ROS (reactive oxygen species) scavenging activities ($OSC_{50}$) in the $Fe^{3+}-EDTA/H_2O_2$ system of DFP and DFP-D were 2 times ($1.84{\pm}0.12{\mu}M$) and 13 times ($0.174{\pm}0.01{\mu}M$), respectively higher than that of L-ascorbic acid. $^1O_2$, one of ROS playing a key role in the skin photo-aging, induces cellular membrane damages. DFP-D ($50{\mu}M$) showed good cell protective effects (${\tau}_{50}=80.2min$) about 2 times more than that of (+)-${\alpha}$-tocopherol (${\tau}_{50}=43.6min$). These results suggest that the great antioxidative activities of DFP and DFP-D could be applied to cosmetic industries as functional cosmetic materials.

Oxidative Stress-dependent Structural and Functional Regulation of 2-cysteine Peroxiredoxins In Eukaryotes Including Plant Cells (산화 스트레스에 의존한 식물 및 진핵세포 2-시스테인 퍼록시레독신의 기능 조절)

  • Jang, Ho-Hee;Kim, Sun-Young;Lee, Sang-Yeol
    • Journal of Plant Biotechnology
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    • v.33 no.1
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    • pp.1-9
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    • 2006
  • Peroxiredoxins (Prxs) are ubiquitously distributed and play important functions in diverse cellular signaling systems. The proteins are largely classified into three groups, such as typical 2-Cys Prx, atypical 2-Cys Prx, and 1-Cys Prx, that are distinguished by their catalytic mechanisms and number of Cys residues. From the three classes of Prxs, the typical 2-Cys Prx containing the two-conserved Cys residues at its N-terminus and C-terminus catalyzes $H_2O_2$ with the use of thioredoxin (Trx) as an electron donor. During the catalytic cycle, the N-terminal Cys residue undergoes a peroxide-dependent oxidation to sulfenic acid, which can be further oxidized to sulfinic acid at the presence of high concentrations of $H_2O_2$ and a Trx system containing Trx, Trx reductase, and NADPH. The sulfinic acid form of 2-Cys Prx is reduced by the action of sulfiredoxin which requires ATP as an energy source. Under the strong oxidative or heat shock stress conditions, 2-Cys Prx in eukaryotes rapidly switches its protein structure from low-molecular-weight species to high-molecular-weight protein structures. In accordance with its structural changes, the protein concomitantly triggers functional switching from a peroxidase to a molecular chaperone, which can protect its substrate denaturation from external stress. In addition to its N-terminal active site, the C-terminal domain including 'YF-motif' of 2-Cys Prx plays a critical role in the structural changes. Therefore, the C-terminal truncated 2-Cys Prxs are not able to regulate their protein structures and highly resistant to $H_2O_2$-dependent hyperoxidation, suggesting that the reaction is guided by the peroxidatic Cys residue. Based on the results, it may be concluded that the peroxidatic Cys of 2-Cys Prx acts as an '$H_2O_2$-sensor' in the cells. The oxidative stress-dependent regulation of 2-Cys Prx provides a means of defense systems in cells to adapt stress conditions by activating intracellular defense signaling pathways. Particularly, 2-Cys Prxs in plants are localized in chloroplasts with a dynamic protein structure. The protein undergoes conformational changes again oxidative stress. Depending on a redox-potential of the chloroplasts, the plant 2-Cys Prx forms super-molecular weight protein structures, which attach to the thylakoid membranes in a reversible manner.