• Title/Summary/Keyword: GluR2

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Amygdala Depotentiation and Fear Extinction

  • Choi, Suk-Woo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2008.04a
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    • pp.33-45
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    • 2008
  • Auditory fear memory is thought to be maintained by fear conditioning-induced potentiation of synaptic efficacy. The conditioning-induced potentiation has been shown to be maintained, at least in part, by enhanced expression of surface AMPA receptor (AMPAR) at excitatory synapses in the lateral amygdala (LA). Depotentiation, reversal of conditioning-induced potentiation, has been proposed as a cellular mechanism for fear extinction. However, a direct link between depotentiation and extinction has not yet been tested. To address this, we applied both ex vivo and in vivo approaches to rats in which fear memory had been consolidated. We found a novel form of ex vivo depotentiation; the depotentiation reversed conditioning-induced potentiation at thalamic input synapses onto the LA (T-LA synapses) ex vivo, and it could be induced only when both NMDA and metabotropic glutamate receptors were co-activated. Extinction returned the enhanced T-LA synaptic efficacy observed in conditioned rats to baseline and occluded the depotentiation. Consistently, extinction reversed conditioning-induced enhancement of surface expression of AMPAR subunits in LA synaptosomal preparations. A GluR2-derived peptide that blocks regulated AMPAR endocytosis inhibited depotentiation, and microinjection of a cell-permeable form of the peptide into the LA attenuated extinction. Our results are consistent with the use of depotentiation to weaken potentiated synaptic inputs onto the LA during extinction, and they provide strong evidence that AMPAR removal at excitatory synapses in the LA underlies extinction. The results described here are in line with previous findings. Neural activity in the LA has been shown to decrease after extinction in the rat and human. The NMDAR dependency of the depotentiation fits nicely with a large body of evidence that fear extinction depends upon amygdala NMDARs. Similarly, blockade of metabotropic glutamate recepotrs in the LA has recently been shown to attenuate fear extinction.

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Two novel mutations in ALDH18A1 and SPG11 genes found by whole-exome sequencing in spastic paraplegia disease patients in Iran

  • Komachali, Sajad Rafiee;Siahpoosh, Zakieh;Salehi, Mansoor
    • Genomics & Informatics
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    • v.20 no.3
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    • pp.30.1-30.9
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    • 2022
  • Hereditary spastic paraplegia is a not common inherited neurological disorder with heterogeneous clinical expressions. ALDH18A1 (located on 10q24.1) gene-related spastic paraplegias (SPG9A and SPG9B) are rare metabolic disorders caused by dominant and recessive mutations that have been found recently. Autosomal recessive hereditary spastic paraplegia is a common and clinical type of familial spastic paraplegia linked to the SPG11 locus (locates on 15q21.1). There are different symptoms of spastic paraplegia, such as muscle atrophy, moderate mental retardation, short stature, balance problem, and lower limb weakness. Our first proband involves a 45 years old man and our second proband involves a 20 years old woman both are affected by spastic paraplegia disease. Genomic DNA was extracted from the peripheral blood of the patients, their parents, and their siblings using a filter-based methodology and quantified and used for molecular analysis and sequencing. Sequencing libraries were generated using Agilent SureSelect Human All ExonV7 kit, and the qualified libraries are fed into NovaSeq 6000 Illumina sequencers. Sanger sequencing was performed by an ABI prism 3730 sequencer. Here, for the first time, we report two cases, the first one which contains likely pathogenic NM_002860: c.475C>T: p.R159X mutation of the ALDH18A1 and the second one has likely pathogenic NM_001160227.2: c.5454dupA: p.Glu1819Argfs Ter11 mutation of the SPG11 gene and also was identified by the whole-exome sequencing and confirmed by Sanger sequencing. Our aim with this study was to confirm that these two novel variants are direct causes of spastic paraplegia.

Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation

  • Seungchan An;Jaemoo Chun;Joohee Lee;Yeong Shik Kim;Minsoo Noh;Hyejin Ko
    • Biomolecules & Therapeutics
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    • v.32 no.5
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    • pp.627-634
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    • 2024
  • Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

Study on the Processing and Compositions of Salted and Dried Mullet Roe (영암산 염건 숭어알의 가공과 조성에 관한 연구)

  • Joe, Sang-June;Rhee, Chong-Ouk;Kim, Dong-Youn
    • Korean Journal of Food Science and Technology
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    • v.21 no.2
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    • pp.242-251
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    • 1989
  • The salted-dried mullet(Mugil japonicus) roe is a kind of traditional food particulary in the area of Young-am gun, Chunnam province. This study was conducted to conform the scientific processing conditions and to evaluate the nutritional quality and changes of major components during storage times. The manufacturing method was that the fresh roe was salted for about 20 hours for the preparation of salted-dried roe, washed by clean waters, drained, shaped a flat piece with 1.2cm thickness by pressing, and spreaded sesame oils on the surface of the salted roe periodically during wind drying for 20 days. The dried roe was blanched in heated water$(80^{\circ}C/3min)$ and packaged the dried product for storages. The fractional compositions of free lipid of wind dried roe were 40% of neutral lipids, 12% of glycolipids and 9% of phospholipids and those of bound lipids were 13% of neutral lipids. 10% of glycolipids and 13% of phospholipids respectively. The major fatty acids of the roe were $C_{16:0}$, $C_{18:0}$, $C_{18:1}$, $C_{18:2}$ and $C_{20:0}$ which was consisted of free and bound lipids in wind drying method during processing and storages. Total amino acids were 99.87g/100g and major amino acids were Glu, Pro, Leu, Lys and CySH and the protein score was average 155% and the chemical score was average 109%. Free amino acids was 1,376mg% that had 50.61% of Pro and the major kinds of those were Tyr and CySH.

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Cross-resistance Between Rifampicin and Rifabutin and Its Relationship with rpoB Gene Mutations in Clinically Isolated MDR-TB Strains (다제내성 결핵 균주에서 리팜핀과 리파부틴간의 교차내성률 및 rpoB 유전자 돌연변이와의 연관성)

  • Kim, Byoung Ju;Oh, Seung Hwan;Cho, Eun Jin;Park, Seung Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.2
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    • pp.171-179
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    • 2006
  • Background : Despite the emerging danger of MDR-TB to human beings, there have only been a limited number of drugs developed to treat MDR-TB since 1970. This study investigated the cross-resistance rate between rifampicin (RFP) and rifabutin (RBU) in order to determine the efficacy of rifabutin in treating MDR-TB. In addition, the results of rifabutin were correlated with the rpoB mutations, which are believed to be markers for MDR-TB and RFP resistance. Methods : The MICs of RBU were tested against 126 clinical isolates of MDR-TB submitted to the clinical laboratory of National Masan TB Hospital in 2004. Five different concentrations ($10-160{\mu}g/ml$) were used for the MICs. The detection of the rpoB mutations was performed using a RFP resistance detection kit with a line probe assay(LiPA), which contains the oligonucleotide probes for 5 wide type and 3 specific mutations (513CCA, 516GTC, and 531TTG) The rpoB mutation was determined by direct sequencing. Results : The rate of cross-resistance between RFP and RBU was 70.5%(74/105) at $20{\mu}g/ml$ RBU(ed note: How much RFP?) Most mutations (86.3%) occurred in the 524~534 codons. The His526Gln, His526Leu, Leu533Pro, Gln513Glu, and Leu511Pro mutations(Ed note: Is this correct?) were associated with the susceptibilty to RBU. Conclusion : Based on the cross-resistance rate between RFP and RBU, RBU may be used effectively in some MDR-TB patients. Therefore, a conventional drug susceptibility test for RBU and a determination of the critical concentration are needed. However, rpoB gene mutation test may be have limited clinical applications in detecting RBU resistance.

Inhibitory Effects of Filiform Acupuncture and Laser Acupuncture at the Points of Zhongzhu($TE_3$).Zulinqi($GB_{41}$) on Neuropathic Pain in the Tibial and Sural Nerve Injury-induced Rats (중저(中渚)($TE_3$).임입(臨泣)($GB_{41}$) 침자 및 레이저침이 백서의 Tibial Nerve와 Sural Nerve 유발 동통 억제에 미치는 영향)

  • Lee, Ju Hee;Lee, Dong Geun;Lee, Ook Jae;Lee, Sang Hyun;Lee, Jung Hun;Jeong, Joo Yong;Cheong, Min Seong;Yang, Tae Jun;Kim, Seon Wook;Cho, Myoung Rae
    • Journal of Acupuncture Research
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    • v.31 no.2
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    • pp.119-134
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    • 2014
  • Objectives : The purpose of this study was to investigate the analgesic effects of filiform acupuncture and laser acupuncture at the points of $TE_3{\cdot}GB_{41}$ in neuropathic pain induced rats. Methods : Neuropathic pain in rats was induced by partial resection of the tibial and sural nerves. Three weeks after the neuropathic surgery, each of the experimental groups(AT, LAT, AT + LAT and LAT + AT) was injected at the $TE_3{\cdot}GB_{41}$ twice per week for three weeks. Results : 1. All of the experimental groups(AT, LAT, AT + LAT and LAT + AT) showed a significant decrease in the plantar withdrawal response of allodynia and the thermal allodynia as compared with the control group. During the early phase, the AT and AT + LAT groups have been marked as more significant than the LAT + AT and LAT groups. 2. The expression of c-Fos significantly decreased in the LAT and LAT + AT groups as compared with the control group. 3. The LAT + AT group showed a significant decrease in Bax as compared with the control group. In each experimental groups(AT, LAT, AT + LAT and LAT + AT), Bcl-2 increased and Bax/Bcl-2 ratio decreased as compared with the control group. 4. The LAT, AT + LAT and LAT + AT groups showed a significant increase in mGluR5 as compared with the control group. Conclusions : These results represented that the filiform acupuncture and laser acupuncture at the $TE_3{\cdot}GB_{41}$ exerted anti-apoptotic and neuroprotective effects on the model of neuropathic pain, thereby suggesting that they should be available for decreasing mechanical allodynia.

Treatment of Ceroidosis for Cultured Flounder, Paralichthys olivaceus -Hematological characteristic of flounder with glutathione supplemented diets- (양식(養殖) 넙치의 Ceroid증(症) 치료(治療)에 대(對)하여 -Glutathione 첨가(添加)에 따른 혈액성상(血液性狀)-)

  • Lee, Chang-Hoon;Ha, Dong-Soo;Chun, Seh-Kyu;Choi, Dong-Lim
    • Journal of fish pathology
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    • v.4 no.2
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    • pp.59-70
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    • 1991
  • In order to investigate the effects of glutathione against ceroidosis on flounder, Paralichthys olivaceus, a serial experiment was carried out at indoor tanks in Cheju province, the southern island of R.O.Korea, from October 1 to November 4 of 1991. The choosed group of flounder for this experiment, ranged from 92 to 122g in body weight, already showed a distinct histological ceroidosis in liver, spleen, kidney about six months before this experiment. They were fed on formulated diets supplemented with glutathione of 0mg, 1mg, 2mg, 5mg, 10mg per kg of diet per day. Some flounders were fed on the decomposed diet as a control continuosuly. Two individuals fed on the experimental diets were cought at an interval 7 days for 35 days and analyzed the values of blood indexs. 1. While the values of RBC, Hb, Ht, MCHC, MCV of flounder fed on the decomposed diet and the glutathione non-supplemented diet were not changed compared with the beginning levels of experiment, those fed on the glutathione supplemented diets, showed markedly increased values from 7th day of experiment and from 21th day of experiment reached to the values of healthy flounder. 2. The variation of TP, Glu, Alp, BUN, TG, T-cho, GOT and GPT were not observed in the groups fed on the control diet and glutathione non-supplemented diet. In contrast, those values in the groups fed on the glutathione supplemented diets were markedly decreased from 7th day and become constant from 21th day. 3. The effect of glutathione supplementation with high concentration in diets showed much better improvements of symptoms concequently, compared with those of low concentration diets.

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Cellulose Degradation and Extracellulat Enzymatic Activity of the Mud Flat in Sunchon Bay (순천만 갯벌 토양의 섬유소 분해능 및 체외효소 활성)

  • 백근식;최지혁;성치남
    • Korean Journal of Microbiology
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    • v.36 no.2
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    • pp.130-135
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    • 2000
  • Decomposition rate of organic matiter in the mud flat of Sunchon Bay was estimated. Physicochemical parameters, cellulose degradation rate. distribution of heterotrophic bacteria, and extracellular enzymatic activities were measured from August 1997 to July 1998. Soil temperatures, water contents, concentration of $PO_4$-P and organic matter were -1-~$30^{\circ}C$, 42.1-53.1%, 0.0779-0.1961 mgig and 1.99-7.64%, respectively. Decomposition rate of cellulose film ranged from 7.7 to 100%imonth, high in summer and low in winter. The number of heterotrophic bacteria ranged from $0.87{\times}10^6 to 3.6{\times}10^7 $CUFsIg dq soil. Enzymatic activities of phosphatase, $\alpha$-D-gluEosidase, $\beta$-D-glucosidase and cellobiohydrolase, which were measured as decomposition rate of methylumbelliferyl(MLiF)-substrate, were 152.23-1779.80 nMIhr, 2.67-202.18 nM/hr, 5.03-258.26 M h r and 3.42-63.07 nM/hr, respectively Cellulose degradaaon rate and extracellular extracellular enzymatic activities were conelated with each other, and showed high correlation coefticiency with soil temperature.

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Antioxidant Effect of HotWaterExtract of Muraenesox cinereus's Skin (갯장어껍질 열수 추출물의 항산화 효과)

  • Shin, Hyun-Jae;Kim, Yoon-Soo;Nam, Hyung-Gun;Na, Myung-Soon;Kim, Mi-Hye;Kang, Hyeong-Bong;Lee, Hee-Duck;Choi, Du-Bok;Choi, On-You;Cha, Wol-Suk
    • KSBB Journal
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    • v.26 no.1
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    • pp.27-32
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    • 2011
  • For the development of functional food and cosmetics using hot water extract of Muraenesox cinereus's skin, contents of vitamin, amino acid and element, and antioxidant activity were investigated. The results are shown as follows: among vitamins, A(0.21mg/100 g), C (78.12mg/100 g), $D_3$ (0.03 mg/100 g), E (1.97 mg/100 g) and Niacin (2.53mg/100 g) were detected, respectively.Mineral contents were an order of K > P > Na > Mg > Ca > Fe and Zn. Contents of total amino acids were an order of Pro > Gly > Arg > Glu > Phe > Ala. Especially, the sum of total amino acids was 27.17 mg/100 mL, which was about 4.0 fold higher than that of free amino acid. DPPH radical scavenging activity of hot water extract of M. cinereus's skin at 25 mg/mL was 63.5% and did not increase at above 50 mg/mL. Activities of antioxidant enzymes in the liver of ethanol-treated rats using hot water extract of M. cinereus's skin were investigated. Compared to control group, activities of ADH and GSH-px were decreased. In the case of CAT and SOD activity, they were increased. These results showed that the hot water extract of M. cinereus's skin can be applied to raw macterial for functional food and cosmetics.

Effect of a microbial phytase on growth performance, plasma parameters and apparent ileal amino acid digestibility in Youxian Sheldrake fed a low-phosphorus corn-soybean diet

  • He, Shaoping;Medrano, R.F.;Yu, Qifang;Cai, Yixin;Dai, Qiuzhong;He, Jianhua
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.10
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    • pp.1442-1449
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    • 2017
  • Objective: This study investigated the effect of microbial phytase supplementation on growth performance, tibia ash, plasma parameters, apparent ileal digestibility (AID) of amino acid (AA) and apparent digestibility of nutrients in Youxian Sheldrakes fed with low-phosphorus (P) cornsoybean diets. Methods: A total of 350 Youxian Sheldrakes (7d old) were randomly divided into 5 treatment groups: positive control (PC) group has adequate available P diet (0.42% and 0.38%, starter and grower), negative control (NC) group were deficient in available P (0.32% and 0.28%, starter and grower) and NC diet was supplemented with 3 levels of microbial phytase (500, 750, and 1,000 U/kg). Results: Dietary supplementation of phytase in NC diet improved the average daily gain, increased the levels of serum calcium (Ca), tibia Ca and P, AID of AA and apparent digestibility of energy and Ca in starter stage (p<0.05). There was an increased (p<0.001) in the utilization of P from 17.3% to 23.9%. Phytase supplementation (1,000 U/kg) has shown that the AID of His, Thr, Val, indispensable AA, Glu, Pro, and dispensable AA was higher (p<0.05) than that of NC. Moreover, phytase supplementation improved (p<0.05) serum and tibia Ca and P, AID of AA and apparent digestibility of dry matter, crude protein, energy, P and Ca, and reduced (p<0.05) feed to gain ratio (F/G) and the levels of serum alkaline phosphatase in grower stage. Likewise, an increase (p<0.001) in the utilization of P was noticed from 12.6% to 17.2%. Supplement phytase at 750 U/kg improved the AID of His, Thr, Asp, Cys, Pro, and Ser (p<0.05). Conclusion: The microbial phytase supplement could improve growth performance, AID of some AA and apparent utilization of other nutrients in Youxian Sheldrakes, and reduce excreta P load to environment.