• Title/Summary/Keyword: direct regulation

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Presynaptic Mechanism Underlying Regulation of Transmitter Release by G Protein Coupled Receptors

  • Takahashi, Tomoyuki;Kajikawa, Yoshinao;Kimura, Masahiro;Saitoh, Naoto;Tsujimoto, Tetsuhiro
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.2
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    • pp.69-76
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    • 2004
  • A variety of G protein coupled receptors (GPCRs) are expressed in the presynaptic terminals of central and peripheral synapses and play regulatory roles in transmitter release. The patch-clamp whole-cell recording technique, applied to the calyx of Held presynaptic terminal in brainstem slices of rodents, has made it possible to directly examine intracellular mechanisms underlying the GPCR-mediated presynaptic inhibition. At the calyx of Held, bath-application of agonists for GPCRs such as $GABA_B$ receptors, group III metabotropic glutamate receptors (mGluRs), adenosine $A_1$ receptors, or adrenaline ${\alpha}2$ receptors, attenuate evoked transmitter release via inhibiting voltage-activated $Ca^{2+}$ currents without affecting voltage-activated $K^+$ currents or inwardly rectifying $K^+$ currents. Furthermore, inhibition of voltage-activated $Ca^{2+}$ currents fully explains the magnitude of GPCR-mediated presynaptic inhibition, indicating no essential involvement of exocytotic mechanisms in the downstream of $Ca^{2+}$ influx. Direct loadings of G protein ${\beta}{\gamma}$ subunit $(G{\beta}{\gamma})$ into the calyceal terminal mimic and occlude the inhibitory effect of a GPCR agonist on presynaptic $Ca^{2+}$ currents $(Ip_{Ca})$, suggesting that $G{\beta}{\gamma}$ mediates presynaptic inhibition by GPCRs. Among presynaptic GPCRs glutamate and adenosine autoreceptors play regulatory roles in transmitter release during early postnatal period when the release probability (p) is high, but these functions are lost concomitantly with a decrease in p during postnatal development.

The functions of mTOR in ischemic diseases

  • Hwang, Seo-Kyoung;Kim, Hyung-Hwan
    • BMB Reports
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    • v.44 no.8
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    • pp.506-511
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    • 2011
  • Mammalian Target of Rapamycin (mTOR) is a serine/threonine kinase and that forms two multiprotein complexes known as the mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). mTOR regulates cell growth, proliferation and survival. mTORC1 is composed of the mTOR catalytic subunit and three associated proteins: raptor, mLST8/$G{\beta}L$ and PRAS40. mTORC2 contains mTOR, rictor, mLST8/$G{\beta}L$, mSin1, and protor. Here, we discuss mTOR as a promising anti-ischemic agent. It is believed that mTORC2 lies down-stream of Akt and acts as a direct activator of Akt. The different functions of mTOR can be explained by the existence of two distinct mTOR complexes containing unique interacting proteins. The loss of TSC2, which is upstream of mTOR, activates S6K1, promotes cell growth and survival, activates mTOR kinase activities, inhibits mTORC1 and mTORC2 via mTOR inhibitors, and suppresses S6K1 and Akt. Although mTOR signaling pathways are often activated in human diseases, such as cancer, mTOR signaling pathways are deactivated in ischemic diseases. From Drosophila to humans, mTOR is necessary for Ser473 phosphorylation of Akt, and the regulation of Akt-mTOR signaling pathways may have a potential role in ischemic disease. This review evaluates the potential functions of mTOR in ischemic diseases. A novel mTOR-interacting protein deregulates over-expression in ischemic disease, representing a new mechanism for controlling mTOR signaling pathways and potential therapeutic strategies for ischemic diseases.

The Study on the Biodegradability and Phosphate, Heavy Metal Contents of Shampoos and Powder Detergents for Clothing (샴푸와 의류용 분말세제의 생분해도와 인산염 및 중금속 함량에 대한 연구)

  • Ko, Young-Shin;Kim, Se-Kyong;Lim, Jong-Wan;Rhu, Chan-Joo;Choi, Sung-Yong
    • Analytical Science and Technology
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    • v.11 no.2
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    • pp.105-111
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    • 1998
  • The biodegradabilities of surfactants were measured for shampoos and powder detergents for clothing(six kinds of each) in domestic market at present. Also the phosphates that cause of eutrophication and heavy metals to have a direct effect on human body were measured. Analysis results show that though they all come up to KS(Korean Industrial Standards), samples containing plenty of sodium ${\alpha}$-olefin sulfonate(AOS), linear alkyl benzene sulfonate(LAS) and synthetic sodium lauryl etoxylate sulfonate (SLES) have the lower biodegradability than the others. It was found that these samples were petroleum surfactants, and the lower biodegradability than surfactants extracted naturally. The contents of phosphates and heavy metals in the samples were under the regulation limits for the cosmetic standards.

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The Actual State of Hospital-based Skill Training in Level 1 Emergency Medical Technician (소방 1급응급구조사의 병원임상수련 술기 실태 조사)

  • Roh, Sang-Gyun;Lee, Jae-Gook;Bang, Sung-Hwan
    • Fire Science and Engineering
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    • v.26 no.5
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    • pp.54-60
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    • 2012
  • This study is the analysis of the actual state of hospital-based training in level 1 emergency medical technicians (EMTs) in fire station. The survey was carried out to 42 fire fighters having level 1 emergency medical technician certification from May 11 to 12 in 2012. The results showed 56.5 %, that the level 1 EMTs of roles had direct experienced. Level 1 EMTs performance frequency of clinical practice that endotracheal intubation 66.9 %, laryngeal mask airway 8.4 %, intravenous access 76.6 %, nitroglycerin sublingual 61.2 %, bronchodilator inhalation 50.0 %, fluid loading 73.8 %, ventilator apply 57.6 %, dextrose injection 57.6 %. It is necessary to investigate the continuous study on the education among the level 1 EMTs and the continuous evaluation and analysis of problems, supplemented of guidebook, practical education programs and regulation upon the operation and management of a hospital-based skill training.

Oxidative Stress, Chromatin Remodeling and Gene Transcription in Inflammation and Chronic Lung Diseases

  • Rahman, Irfan
    • BMB Reports
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    • v.36 no.1
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    • pp.95-109
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    • 2003
  • Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.

Analysis of Cosmic Radiation Dose of People by Abroad Travel (일반인들의 항공여객기 이용 시 우주방사선 피폭선량 비교 분석)

  • Jang, Donggun;Shin, Sanghwa
    • Journal of radiological science and technology
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    • v.41 no.4
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    • pp.339-344
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    • 2018
  • Humans received an exposure dose of 2.4 mSv of natural radiation per year, of which the contribution of spacecraft accounts for about 75%. The crew of the aircraft has increased radiation exposure doses based on cosmic radiation safety management regulations There is no reference to air passengers. Therefore, in this study, we measured the radiation exposure dose received in the sky at high altitude during flight, and tried to compare the radiation exposure dose received by ordinary people during flight. We selected 20 sample specimens, including major tourist spots and the capital by continent with direct flights from Incheon International Airport. Using the CARI-6/6M model and the NAIRAS model, which are cosmic radiation prediction models provided at the National Radio Research Institute, we measured the cosmic radiation exposure dose by the selected flight and departure/arrival place. In the case of exposure dose, Beijing was the lowest at $2.87{\mu}Sv$ (NAIRAS) and $2.05{\mu}Sv$ (CARI - 6/6M), New York had the highest at $146.45{\mu}Sv$ (NAIRAS) and $79.42{\mu}Sv$ (CARI - 6/6M). We found that the route using Arctic routes at the same time and distance will receive more exposure dose than other paths. While the dose of cosmic radiation to be received during flight does not have a decisive influence on the human body, because of the greater risk of stochastic effects in the case of frequent flights and in children with high radiation sensitivity Institutional regulation should be prepared for this.

Visualization of Hepatitis B Virus (HBV) Surface Protein Binding to HepG2 Cells

  • Lee, Dong-Gun;Park, Jung-Hyun;Choi, Eun-A;Han, Mi-Young;Kim, Kil-Lyong;Hahm, Kyung-Soo
    • BMB Reports
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    • v.29 no.2
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    • pp.175-179
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    • 1996
  • Viral surface proteins are known to play an essential role in attachment of the virus particle to the host cell membrane. In case of the hepatitis B virus (HBV) several reports have described potential receptors on the target cell side, but no definite receptor protein has been isolated yet. As for the viral side, it has been suggested that the preS region of the envelope protein, especially the preS1 region, is involved in binding of HBV to the host cell. In this study, preS1 region was recombinantly expressed in the form of a maltose binding protein (MBP) fusion protein and used to identify and visualize the expression of putative HBV receptor(s) on the host cell. Using laser scanned confocal microscopy and by FACS analysis, MBP-preS1 proteins were shown to bind to the human hepatoma cell line HepG2 in a receptor-ligand specific manner. The binding kinetic of MBP-preS1 to its cellular receptor was shown to be temperature and time dependent. In cells permeabilized with Triton X-100 and treated with the fusion protein, a specific staining of the nuclear membrane could be observed. To determine the precise location of the receptor binding site within the preS1 region, several short overlapping peptides from this region were synthesized and used in a competition assay. In this way the receptor binding epitope in preS1 was revealed to be amino acid residues 27 to 51, which is in agreement with previous reports. These results confirm the significance of the preS1 region in virus attachment in general, and suggest an internalization pathway mediated by direct attachment of the viral particle to the target cell membrane.

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A study on the detection of DDoS attack using the IP Spoofing (IP 스푸핑을 통한 DDoS 공격 탐지 방안에 대한 연구)

  • Seo, Jung-Woo;Lee, Sang-Jin
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.25 no.1
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    • pp.147-153
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    • 2015
  • Since the DoS(Denial of Service) attack is still an important vulnerable element in many web service sites, sites including public institution should try their best in constructing defensive systems. Recently, DDoS(Distributed Denial of Service) has been raised by prompting mass network traffic that uses NTP's monlist function or DoS attack has been made related to the DNS infrastructure which is impossible for direct defense. For instance, in June 2013, there has been an outbreak of an infringement accident where Computing and Information Agency was the target. There was a DNS application DoS attack which made the public institution's Information System impossible to run its normal services. Like this, since there is a high possibility in having an extensive damage due to the characteristics of DDoS in attacking unspecific information service and not being limited to a particular information system, efforts have to be made in order to minimize cyber threats. This thesis proposes a method for using TTL (Time To Live) value in IP header to detect DDoS attack with IP spoofing, which occurs when data is transmitted under the agreed regulation between the international and domestic information system.

An Analytical Study by Variation of Die and Plug Angle in Drawing Process for the Strength Optimization of Ultra High Pressure Common Rail Fuel Injection Tube Raw Material (초고압 커먼레일 연료분사튜브 원재료 강성 최적화를 위한 인발 공정에서의 Die와 Plug 각도 변경에 따른 해석적 연구)

  • Ahn, Seoyeon;Park, Jungkwon;Kim, Yonggyeom;Won, Jongphil;Kim, Hyunsoo;Kang, Insan
    • Transactions of the Korean Society of Automotive Engineers
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    • v.24 no.3
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    • pp.338-344
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    • 2016
  • The study is actively being performed to increase fuel injection pressure of common rail system among countermeasures to meet the emission regulation strengthen of the Diesel engine. The common rail fuel injection tube in such ultra high pressure common rail system has the weakest structural characteristics against vibration that is generated by fuel injection pressure and pulsation during engine operation and driving. Thus the extreme durability is required for common rail fuel injection tube, and the drawing process is being magnified as the most important technical fact for strength of seamless pipe that is the raw material of common rail tube. In this respect, we analyzed the characteristic of dimension and stress variation of the ultra high pressure common rail fuel injection tube by variation of Die and Plug angle in drawing process. Based on the analysis, we tried to obtain the raw material strength of common rail fuel injection tube for applying to the ultra high pressure common rail system. As a result, Plug angle is more important than entry angle of Die and we could obtain the target dimension and strength of the ultra high pressure common rail fuel injection tube through optimization of Plug angle.

Effects of Central GABA and Glutamate on Blood Pressure and Single Unit Spikes in the RVLM of Rats

  • Park, Jae-Sik;Lee, Zee-Ihn;Jang, Jae-Hee;Ahn, Dong-Kuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.3
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    • pp.149-154
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    • 2002
  • The blood pressure (BP) is regulated by the nervous system and humoral factors, such as renin- angiotensin system, vasopressin and others. In the present study, we examined the central effects of glutamate and GABA on the cardiovascular regulation by injection of these substances into the lateral ventricle and also investigated the relationship between these central effects and the action of angiotensin II (Ang). Male Sprague Dawley rats, $350{\sim}400$ g, were anesthetized with urethane and instrumented with an arterial catheter for direct measurement of BP and heart rate (HR), and an guide cannula in the lateral ventricle for drug injection. A glass microelectode was inserted into the rostral ventrolateral medulla (RVLM) for recording single unit spikes. Barosensitive neurons were identified by changes of single unit spikes in RVLM following intravenous injection of nitroprusside and phenylephrine. The effects of GABA and glutamate injected into the lateral ventricle were studied in single neuronal activity of the RVLM in addition to changes in BP and heart rate, and compared the results before and after treatment with intravenous losartan, nonpeptide Ang II-type 1 receptor antagonist (1 mg/100 g BW). Intracerebroventricular administration of GABA decreased systolic blood pressure (SBP) and HR, but increased the firing rates in the RVLM. However, intracerebroventricular glutamate injection produced effects opposite to GABA. After pretreatment of intravenous losartan, the central effects of GABA on BP and firing rate in the RVLM were significantly attenuated and that of glutamate showed a tendency of attenuation. These results suggested that central GABA and glutamate regulated BP and firing rates in RVLM were inversely related to BP change. The central effects of GABA or glutamate on the autonomic nervous function were modulated by humoral factor, Ang II, by maintaining BP.