• Title/Summary/Keyword: Signalling

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Notch Is Not Involved in Physioxia-Mediated Stem Cell Maintenance in Midbrain Neural Stem Cells

  • Anne Herrmann;Anne K. Meyer;Lena Braunschweig;Lisa Wagenfuehr;Franz Markert;Deborah Kolitsch;Vladimir Vukicevic;Christiane Hartmann;Marlen Siebert;Monika Ehrhart-Bornstein;Andreas Hermann;Alexander Storch
    • International Journal of Stem Cells
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    • v.16 no.3
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    • pp.293-303
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    • 2023
  • Background and Objectives: The physiological oxygen tension in fetal brains (~3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1𝛼/Notch regulatory interactions as well as our observations that Hif-1𝛼 and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance. Methods and Results: Here we found that physioxia (3% O2) compared to normoxia (21% O2) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions. Conclusions: Notch signalling does not influence the fate decision of midbrain NSCs cultured in vitro in physioxia, where other factors like Hif-1𝛼 might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.

Performance Evaluation of Dynamic signalling Period Allocation Algorithm for Wireless ATM MAC Protocols under Mixed Traffic Conditions (무선 ATM MAC 프로토콜을 위한 동적 신호 주기 할당 알고리즘의 다양한 트래픽 환경에서의 성능평가)

  • 강상욱;신요안;최승철
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.25 no.5B
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    • pp.820-829
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    • 2000
  • In this paper, DSPA(Dynamic Signalling Period Allocation) algorithm that has been proposed by the authors for MAC(Medium Access Control) protocols in W-ATM(Wireless Asynchronous Transfer Mode) is applied to mixed traffic conditions composed of various service classes. We investigate the bandwidth utilization efficiency and quality of service(QoS) fulfillment by the DSPA algorithm used in W-ATM MAC protocols. Simulation results indicate that the DSPA algorithm significantly increases the throughput of the system with the minimum control overhead. Moreover, QoS of each service class is well satisfied by proper and fair channel allocation to different service classes according to their requirements.

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GP130 cytokines and bone remodelling in health and disease

  • Sims, Natalie A.;Walsh, Nicole C.
    • BMB Reports
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    • v.43 no.8
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    • pp.513-523
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    • 2010
  • Cytokines that bind to and signal through the gp130 co-receptor subunit include interleukin (IL)-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and ciliary neutrophic factor (CNTF). Apart from contributing to inflammation, gp130 signalling cytokines also function in the maintenance of bone homeostasis. Expression of each of these cytokines and their ligand-specific receptors is observed in bone and joint cells, and bone-active hormones and inflammatory cytokines regulate their expression. gp130 signalling cytokines have been shown to regulate the differentiation and activity of osteoblasts, osteoclasts and chondrocytes. Furthermore, cytokine and receptor specific gene-knockout mouse models have identified distinct roles for each of these cytokines in regulating bone resorption, bone formation and bone growth. This review will discuss the current models of paracrine and endocrine actions of gp130-signalling cytokines in bone remodelling and growth, as well as their impact in pathologic bone remodelling evident in periodontal disease, rheumatoid arthritis, spondylarthropathies and osteoarthritis.

The mTOR Signalling Pathway in Cancer and the Potential mTOR Inhibitory Activities of Natural Phytochemicals

  • Tan, Heng Kean;Moad, Ahmed Ismail Hassan;Tan, Mei Lan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6463-6475
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    • 2014
  • The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.

A Conclusive Review on Amyloid Beta Peptide Induced Cerebrovascular Degeneration and the Mechanism in Mitochondria

  • Merlin, Jayalal L.P.
    • Journal of Integrative Natural Science
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    • v.6 no.3
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    • pp.125-137
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    • 2013
  • Promising evidence suggests that amyloid beta peptide ($A{\beta}$), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in $A{\beta}$-induced apoptosis of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling cascade upstream of mitochondria entails $A{\beta}$ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in $A{\beta}$-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by $A{\beta}$ to induce death of non-neuronal cells are complex. Understanding these apoptosis signalling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular $A{\beta}$ deposition.

Access Control for Integrated Voice and Data Traffic with Waiting Time Signalling over Common Packet Channel in 3GPP (음성과 데이터 트래픽을 전송하는 3GPP 공통 패킷 채널에서 대기시간을 갖는 채널 접속 제어)

  • Park, Sang-Kyu;Lim, In-Chun
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.27 no.8B
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    • pp.780-786
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    • 2002
  • In this paper several access schemes for voice and data packet over CPCH with waiting time signalling are proposed. Waiting time signalling is used for reducing the excessive attempt of UE when all the CPCH channel resources is being used by other UEs. The proposed schemes in this paper are better than other schemes in view of the voice/data packets? dropping probability, average access attempt to transmit voice/data packets successfully and the average throughput.

신호중계교환기 SMX-1에서 신호연결 제어부의 설계 및 구현

  • Yang, Sun-Seong;Lee, Yeong-Hui
    • ETRI Journal
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    • v.14 no.3
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    • pp.1-15
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    • 1992
  • Stand-slone 신호 중계 교환기인 SMX-1(Signalling Message eXchange No.1)은 통신망의 신경계인 공통선 신호망(Common Channel Signalling Network)의 하부 구조를 구성하는 시스팀이다. SMX-1에 총괄명 번역서비스를 수용하게 되면 통신망 사용자에게 통신망 내부의 구성 및 구성 요소의 변화에 구속되지 않고 지속적인 지능망 서비스를 제공할 수 있게 된다. 본 연구에서는 SMX-1의 설계 이념에 부합되도록 신호연결 제어부의 기능을 소프트웨어 및 하드웨어적으로 분산화하여 설계, 구현함으로써 SMX-1의 고신뢰성 및 신속성을 추구하였다. 소프트웨어적으로는 총괄명번역 서비스 제공을 위해 국제 전신 전화 자문 회의(CCITT)권고 Q.711-Q.714에서 정의하고 있는 신호연결 제어부(SCCP:Signalling Connection Control Part)의 기능을 관리 기능(SCMG : SCCP Management Part)과 루팅 제어 기능(SCRC : SCCP Routing Control Part)으로 분리하여 각각의 기능을 이중화하여 설계, 구현하였다. 하드웨어적으로는 관리 기능을 하나의 보드로 집중화하고 루팅 제어 기능을 여러개의 보드로 분산화하였다. 분산되어 있는 루팅 제어기능이 총괄명번역 서비스를 수행하기 위하여 사용하는 루팅 제어 데이터의 일치성을 유지하기 위하여, 관리 기능에 루팅 제어 데이터를 총괄적으로 관리하는 루팅 제어 데이터 관리 기능(RCDMFB : Routing Control Data Management Function Block)과 운용 관리 기능 (OMS : Operation and Management Subsystem)의 제원관리 지원기능을 구현하였다.

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N-terminal GNBP homology domain of Gram-negative binding protein 3 functions as a beta-1,3-glucan binding motif in Tenebrio molitor

  • Lee, Han-Na;Kwon, Hyun-Mi;Park, Ji-Won;Kurokawa, Kenji;Lee, Bok-Luel
    • BMB Reports
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    • v.42 no.8
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    • pp.506-510
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    • 2009
  • The Toll signalling pathway in invertebrates is responsible for defense against Gram-positive bacteria and fungi, leading to the expression of antimicrobial peptides via NF-$\kappa$B-like transcription factors. Gram-negative binding protein 3 (GNBP3) detects beta-1,3-glucan, a fungal cell wall component, and activates a three step serine protease cascade for activation of the Toll signalling pathway. Here, we showed that the recombinant N-terminal domain of Tenebrio molitor GNBP3 bound to beta-1,3-glucan, but did not activate down-stream serine protease cascade in vitro. Reversely, the N-terminal domain blocked GNBP3-mediated serine protease cascade activation in vitro and also inhibited beta-1,3-glucan-mediated antimicrobial peptide induction in Tenebrio molitor larvae. These results suggest that the N-terminal GNBP homology domain of GNBP3 functions as a beta-1,3-glucan binding domain and the C-terminal domain of GNBP3 may be required for the recruitment of immediate down-stream serine protease zymogen during Toll signalling pathway activation.

Complex Interplay between the RUNX Transcription Factors and Wnt/β-Catenin Pathway in Cancer: A Tango in the Night

  • Sweeney, Kerri;Cameron, Ewan R.;Blyth, Karen
    • Molecules and Cells
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    • v.43 no.2
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    • pp.188-197
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    • 2020
  • Cells are designed to be sensitive to a myriad of external cues so they can fulfil their individual destiny as part of the greater whole. A number of well-characterised signalling pathways dictate the cell's response to the external environment and incoming messages. In healthy, well-ordered homeostatic systems these signals are tightly controlled and kept in balance. However, given their powerful control over cell fate, these pathways, and the transcriptional machinery they orchestrate, are frequently hijacked during the development of neoplastic disease. A prime example is the Wnt signalling pathway that can be modulated by a variety of ligands and inhibitors, ultimately exerting its effects through the β-catenin transcription factor and its downstream target genes. Here we focus on the interplay between the three-member family of RUNX transcription factors with the Wnt pathway and how together they can influence cell behaviour and contribute to cancer development. In a recurring theme with other signalling systems, the RUNX genes and the Wnt pathway appear to operate within a series of feedback loops. RUNX genes are capable of directly and indirectly regulating different elements of the Wnt pathway to either strengthen or inhibit the signal. Equally, β-catenin and its transcriptional co-factors can control RUNX gene expression and together they can collaborate to regulate a large number of third party co-target genes.

Photobiomodulation therapy activates YAP and triggers proliferation and dedifferentiation of Müller glia in mammalian retina

  • Seo-Yeon Kim;Myung-Jun Song;In-Beom Kim;Tae Kwan Park;Jungmook Lyu
    • BMB Reports
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    • v.56 no.9
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    • pp.502-507
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    • 2023
  • Photobiomodulation therapy has been proposed as a promising therapeutic approach for retinal degenerative diseases. However, its effect on the regenerative capacity in mammalian retina and its intracellular signalling mechanisms remain unknown. Here, we show that photobiomodulation with 670 nm light stimulates Müller glia cell cycle re-entry and dedifferentiation into a progenitor-like state in both the uninjured and injured retina. We also find that 670 nm light treatment inhibits the Hippo pathway, which is activated in Müller glia following NaIO3-induced retinal injury. YAP, a major downstream effector of the Hippo signalling pathway was translocated into the nucleus of Müller glia along with YAP dephosphorylation in retina treated with 670 nm light. Deficiency of YAP attenuated Müller glia cell cycle re-entry and dedifferentiation. Our data reveal that the Hippo-YAP signalling pathway is associated with the photostimulatory effect on regenerative response in mammalian retina, and suggest a potential therapeutic strategy for retinal degenerative diseases.