• Title/Summary/Keyword: Functional modulation

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US28, a Virally-Encoded GPCR as an Antiviral Target for Human Cytomegalovirus Infection

  • Lee, Sungjin;Chung, Yoon Hee;Lee, Choongho
    • Biomolecules & Therapeutics
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    • v.25 no.1
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    • pp.69-79
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    • 2017
  • Viruses continue to evolve a new strategy to take advantage of every aspect of host cells in order to maximize their survival. Due to their central roles in transducing a variety of transmembrane signals, GPCRs seem to be a prime target for viruses to pirate for their own use. Incorporation of GPCR functionality into the genome of herpesviruses has been demonstrated to be essential for pathogenesis of many herpesviruses-induced diseases. Here, we introduce US28 of human cytomegalovirus (HCMV) as the best-studied example of virally-encoded GPCRs to manipulate host GPCR signaling. In this review, we wish to summarize a number of US28-related topics including its regulation of host signaling pathways, its constitutive internalization, its structural and functional analysis, its roles in HCMV biology and pathogenesis, its proliferative activities and role in oncogenesis, and pharmacological modulation of its biological activities. This review will aid in our understanding of how pathogenic viruses usurp the host GPCR signaling for successful viral infection. This kind of knowledge will enable us to build a better strategy to control viral infection by normalizing the virally-dysregulated host GPCR signaling.

Nitric Oxide Modulation of GABAergic Synaptic Transmission in Mechanically Isolated Rat Auditory Cortical Neurons

  • Lee, Jong-Ju
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.6
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    • pp.461-467
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    • 2009
  • The auditory cortex (A1) encodes the acquired significance of sound for the perception and interpretation of sound. Nitric oxide (NO) is a gas molecule with free radical properties that functions as a transmitter molecule and can alter neural activity without direct synaptic connections. We used whole-cell recordings under voltage clamp to investigate the effect of NO on spontaneous GABAergic synaptic transmission in mechanically isolated rat auditory cortical neurons preserving functional presynaptic nerve terminals. GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) in the A1 were completely blocked by bicuculline. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), reduced the GABAergic sIPSC frequency without affecting the mean current amplitude. The SNAP-induced inhibition of sIPSC frequency was mimicked by 8-bromoguanosine cyclic 3',5'-monophosphate, a membrane permeable cyclic-GMP analogue, and blocked by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a specific NO scavenger. Blockade of presynaptic $K^+$ channels by 4-aminopyridine, a $K^+$ channel blocker, increased the frequencies of GABAergic sIPSCs, but did not affect the inhibitory effects of SNAP. However, blocking of presynaptic $Ca^{2+}$ channels by $Cd^{2+}$, a general voltage-dependent $Ca^{2+}$ channel blocker, decreased the frequencies of GABAergic sIPSCs, and blocked SNAP-induced reduction of sIPSC frequency. These findings suggest that NO inhibits spontaneous GABA release by activation of cGMP-dependent signaling and inhibition of presynaptic $Ca^{2+}$ channels in the presynaptic nerve terminals of A1 neurons.

Induction of Functional Changes of Dendritic Cells by Silica Nanoparticles

  • Kang, Kyeong-Ah;Lim, Jong-Seok
    • IMMUNE NETWORK
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    • v.12 no.3
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    • pp.104-112
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    • 2012
  • Silica is one of the most abundant compounds found in nature. Immoderate exposure to crystalline silica has been linked to pulmonary disease and crystalline silica has been classified as a Group I carcinogen. Ultrafine (diameter <100 nm) silica particles may have different toxicological properties compared to larger particles. We evaluated the effect of ultrafine silica nanoparticles on mouse bone marrow-derived dendritic cells (BMDC) and murine dendritic cell line, DC2.4. The exposure of dendritic cells (DCs) to ultrafine silica nanoparticles showed a decrease in cell viability and an induction of cell death in size- and concentration-dependent manners. In addition, in order to examine the phenotypic changes of DCs following co-culture with silica nanoparticles, we added each sized-silica nanoparticle along with GM-CSF and IL-4 during and after DC differentiation. Expression of CD11c, a typical DC marker, and multiple surface molecules such as CD54, CD80, CD86, MHC class II, was changed by silica nanoparticles in a size-dependent manner. We also found that silica nanoparticles affect inflammatory response in DCs in vitro and in vivo. Finally, we found that p38 and NF-${\kappa}B$ activation may be critical for the inflammatory response by silica nanoparticles. Our data demonstrate that ultrafine silica nanoparticles have cytotoxic effects on dendritic cells and immune modulation effects in vitro and in vivo.

Presynatic Expression of HCN Channel Subunits in Cerebellar Basket Cells

  • Yi, Jee-Hyun;Park, Kyung-Joon;Kang, Shin-Jung;Shin, Ki-Soon
    • Animal cells and systems
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    • v.11 no.2
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    • pp.199-204
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    • 2007
  • HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, whose gene family consists of four subunits (HCN1-4), mediate depolarizing cation currents and contribute to controlling neuronal excitability. In the present study, immunohistochemical and electrophysiological approaches were used to elucidate the role of HCN channels in the cerebellum. Immunohistochemical labeling for HCN1 and HCN2 channels revealed localized expression of both channels at pinceau, the specialized structure of presynaptic axon terminals of basket cells. To determine the functional role of the presynaptic HCN channels, spontaneous inhibitory postsynaptic currents (IPSCs) were recorded from Purkinje cells, the main synaptic targets of basket cells in the cerebellum. While activation of HCN channels by 8-bromo-cAMP increased amplitude of spontaneous IPSCs, blockade of the activated HCN channels by subsequent ZD7288 application reduced the amplitude of spontaneous IPSCs to the level far below the control. Our results imply that modulation of HCN1 and HCN2 channels in presynaptic terminals of basket cells regulates neurotransmitter release, thereby controlling the excitability of Purkinje cells.

Pain Physiology and Principles of Physical Therapy (통증 생리와 물리치료 원리)

  • Kim, Jong-Man;Ahn, Duck-Hyun
    • Physical Therapy Korea
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    • v.5 no.2
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    • pp.106-117
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    • 1998
  • The pain is common among individuals with physical disabilities. It can interfere with therapy since patients with pain can become uncooperative and reluctant to move. This paper reviews the natural physiological mechanisms that can reduce pain perception, and considers physiological mechanisms which contribute to clinical pain by describing how the pain system changes its sensitivity depending upon the body's needs. The peripheral and central mechanisms contributing to sensitised nociceptive system are described with reference to the symptoms of clinical pain such as hyperalgesia, allodynia sopntaneous 'on-going'-projected and referred pain. It is suggested that in some chronic pain the nociceptive system maintains a state of sensitivity despite the absence of on-going tissue damage and under such circumstances the nociceptive system itself may have become dysfunctional. Such situations are often initiated by damage to nervous tissue which results in changes in the activity and organization of neuronal circuits within the central nervous system. The ability of the nociceptive system to operate in a suppressed state is also discussed with reference to pain modulation. The physical therapist can help facilitate the activation of these mechanisms through a combination of noninvasive modalities, functional activities, and the therapeutic use of self.

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Inhibition of The Stem Cell Factor-Induced Migration of Mast Cells by Dexamethasone

  • Jeong, Hyun-Ja;Hong, Seung-Heon;Park, Rae-Kil;Kim, Hyung-Min
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.76-76
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    • 2003
  • Mast cells accumulation can be causally related with several allergic inflammations. Previous work has demonstrated that glucocorticoids decreased tissue mast cell number and stem cell factor (SCF)-induced migration of mast cells required p38 mitogen-activated protein kinase (MAPK) activation. In the present study, we investigated the effects of dexamethasone on SCF-induced migration of rat peritoneal mast cells (RPMCs). SCF significantly induced migration of RPMCs at 4 h. Dexamethasone dose-dependently inhibited SCF-induced migration of RPMCs (about 90.1% at 100 nM, P<0.05). MAPK p38 inhibitor, SB203580 (20 ${\mu}$M) also inhibited the SCF-induced migration. The ability of SCF to enhance morphological alteration and F -actin formation was also abolished by treatment of dexamethasone. Dexamethasone inhibited SCF-induced p38 MAPK activation to near basal level and induced the MKP-1 expression. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment of dexamethasone or SB203580 (p<0.01). Our results show that dexamethasone potently regulates SCF -induced migration, p38 MAPK activation and inflammatory cytokine production through expression of MKP-l protein in RPMCs. Such modulation may have functional consequences during dexamethasone treatment, especially mast cell-mediated allergic inflammation disorders.

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Classification, Structure, and Bioactive Functions of Oligosaccharides in Milk

  • Mijan, Mohammad Al;Lee, Yun-Kyung;Kwak, Hae-Soo
    • Food Science of Animal Resources
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    • v.31 no.5
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    • pp.631-640
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    • 2011
  • Milk oligosaccharides are the complex mixture of six monosaccharides namely, D-glucose, D-galactose, N-acetyl-glucosamine, N-acetyl-galactosamine, L-fucose, and N-acetyl-neuraminic acid. The mixture is categorized as neutral and acidic classes. Previously, 25 oligosaccharides in bovine milk and 115 oligosaccharides in human milk have been characterized. Because human intestine lacks the enzyme to hydrolyze the oligosaccharide structures, these substances can reach the colon without degradation and are known to have many health beneficial functions. It has been shown that this fraction of carbohydrate can increase the bifidobacterial population in the intestine and colon, resulting in a significant reduction of pathogenic bacteria. The role of milk oligosaccharides as a barrier against pathogens binding to the cell surface has recently been demonstrated. Milk oligosaccharides have the potential to produce immuno-modulation effects. It is also well known that oligosaccharides in milk have a significant influence on intestinal mineral absorption and in the formation of the brain and central nervous system. Due to its structural resemblance, bovine milk is considered to be the most potential source of oligosaccharides to produce the same effect of oligosaccharides present in human milk. This review describes the characteristics and potential health benefits of milk oligosaccharides as well as the prospects of oligosaccharides in bovine milk for use in functional foods.

A Study on the Implementation of Wireless Modem for Packet Transmission (패킷 전송용 무선 모뎀 구현에 관한 연구)

  • 염지운;조성배;조병록;최형진
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.19 no.8
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    • pp.1536-1547
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    • 1994
  • This paper presented the implementation and design of narrowband wireless MODEM for packet transmission. The MODEM consists of transmitter, receiver, and the control unit. The BPSK modulation with narrowband filtering is used. The receiver consists of functional modules such as carrier recovery, bit synchronization, lock detector, etc. We evaluated the performance of packet transmission with three MODEM sets implemented in distributed packet radio network. We confirmed the transmission of packetized data through RS232C port of PC. Also, we presented results of experimental data by using measuring instruments. The implemented MODEM in this paper is expected to be useful for the design of wireless LAN system.

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Design & Test of Stereo Camera Ground Model for Lunar Exploration

  • Heo, Haeng-Pal;Park, Jong-Euk;Shin, Sang-Youn;Yong, Sang-Soon
    • Korean Journal of Remote Sensing
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    • v.28 no.6
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    • pp.693-704
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    • 2012
  • Space-born remote sensing camera systems tend to be developed to have very high performances. They are developed to provide extremely small ground sample distance, wide swath width, and good MTF (Modulation Transfer Function) at the expense of big volume, massive weight, and big power consumption. Therefore, the camera system occupies relatively big portion of the satellite bus from the point of mass and volume. However, the camera systems for lunar exploration don't need to have such high performances. Instead, it should be versatile for various usages under various operating environments. It should be light and small and should consume small power. In order to be used for national program of lunar exploration, electro-optical versatile camera system, called MAEPLE (Multi-Application Electro-Optical Payload for Lunar Exploration), has been designed after the derivation of camera system requirements. A ground model of the camera system has been manufactured to identify and secure relevant key technologies. The ground model was mounted on an aircraft and checked if the basic design concept would be valid and versatile functions implemented on the camera system would worked properly. In this paper, results of design and functional test performed with the field campaigns and air-born imaging are introduced.

Design and Test of On-Board Flight Data Acquisition System based on the RS485 Star Network (RS485 Star 구조의 비행체 탑재용 데이터 수집시스템 구현 및 성능시험)

  • Lee, Sang-Rae;Lee, Jae-Deuk
    • Journal of the Korean Society for Aeronautical & Space Sciences
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    • v.32 no.7
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    • pp.83-90
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    • 2004
  • This paper describes on-board decentralized data acquisition system that acquires and encodes the numerous sensor data distributed on the big flight vehicles efficiently. The system's sub-units which have one encoder unit and several remote units were designed and simulated according to the communication protocols and the control, sequence logics based on the FPGA chip. And we have made the functional verification of the acquisition, collection and formatting of remote analog and digital data for the manufactured hardwares.