• 제목/요약/키워드: ${\pi}-{\pi}$ interactions

검색결과 122건 처리시간 0.024초

Dephosphorylation of p53 Ser 392 Enhances Trimethylation of Histone H3 Lys 9 via SUV39h1 Stabilization in CK2 Downregulation-Mediated Senescence

  • Park, Jeong-Woo;Bae, Young-Seuk
    • Molecules and Cells
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    • 제42권11호
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    • pp.773-782
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    • 2019
  • Cellular senescence is an irreversible form of cell cycle arrest. Senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHFs). Protein kinase CK2 (CK2) downregulation can induce trimethylation of histone H3 Lys 9 (H3K9me3) and SAHFs formation by activating SUV39h1. Here, we present evidence that the PI3K-AKT-mTOR-reactive oxygen species-p53 pathway is necessary for CK2 downregulation-mediated H3K9me3 and SAHFs formation. CK2 downregulation promotes SUV39h1 stability by inhibiting its proteasomal degradation in a p53-dependent manner. Moreover, the dephosphorylation status of Ser 392 on p53, a possible CK2 target site, enhances the nuclear import and subsequent stabilization of SUV39h1 by inhibiting the interactions between p53, MDM2, and SUV39h1. Furthermore, $p21^{Cip1/WAF1}$ is required for CK2 downregulation-mediated H3K9me3, and dephosphorylation of Ser 392 on p53 is important for efficient transcription of $p21^{Cip1/WAF}$. Taken together, these results suggest that CK2 downregulation induces dephosphorylation of Ser 392 on p53, which subsequently increases the stability of SUV39h1 and the expression of $p21^{Cip1/WAF1}$, leading to H3K9me3 and SAHFs formation.

저비용 대화 상호작용 정보 수집 시스템 설계 (Low-cost system design to collect interaction information during conversation)

  • 조상진;박재현;홍운기
    • 한국산업정보학회논문지
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    • 제28권1호
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    • pp.9-16
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    • 2023
  • 산업 현장에서 해결해야 할 문제가 다양해지고 복잡해짐에 따라 팀 활동의 중요성이 더욱 커지고 있다. 팀의 성과는 팀원 성과의 단순한 합이 아니라 팀 내 상호작용에 따라 시너지를 얻거나 감소하기도 한다. 이러한 팀 활동에 관한 분석적 연구를 진행하기 위해 ICT 기술을 이용한 연구가 이루어졌지만, 이러한 기술을 개발하고 활용하는 것은 시간과 비용이 많이 소요되어 현장 실무자들과 연구자가 활용하기 어려운 한계점이 있다. 본 연구에서는 아두이노와 라즈베리 파이를 활용하여 저비용으로 대화 상호작용 정보를 수집하는 시스템을 설계한 뒤 여러 장치로부터 대화 상호작용 정보를 수집하여 데이터베이스에 올바르게 저장됨을 검증하였다. 본 연구에서 제안하는 저비용 정보 수집 시스템을 통해 산업정보의 다양한 분야에서 후속 연구가 이루어질 수 있는 환경을 조성하고자 한다.

작약감초탕 가 현호색의 항염증 기전에 대한 네트워크 약리학적 분석 (Network pharmacology analysis of Jakyakgamchotang with corydalis tuber for anti-inflammation)

  • 김영식;김홍준;박한빈;이승호
    • 대한한의학방제학회지
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    • 제32권1호
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    • pp.39-49
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    • 2024
  • Objectives : The purpose of this study was to investigate the molecular targets and pathways of anti-inflammatory effects of Jakyakgamchotang with corydalis tuber (JC) using network pharmacology. Methods : The compounds in constituent herbal medicines of JC were searched in TCM systems pharmacology (TCMSP). Target gene informations of the components were collected using chemical-target interactions database provided by Pubchem. Afterwards, network analysis between compounds and inflammation-related target genes was performed using cytoscape. Go enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on inflammation-related targets using DAVID database. Results : 70 active compounds related to inflammation were identified, and 295 target genes related to the anti-inflammatory activity of the compound of JC were identified. In the Go biological process DB and KEGG pathway DB, "inflammatory response", "cellular response to lipopolysaccharide", "positive regulation of interleukin-6 production", and "positive regulation of protein kinase B. signaling", "positive regulation of ERK1 and ERK2 cascade", "positive regulation of I-kappaB kinase/NF-kappaB signaling", "negative regulation of apoptotic process", and "PI3K-Akt signaling pathway" were found to be mechanisms related to the anti-inflammatory effects related to the target genes of JC. The main compounds predicted to be involved in the anti-inflammatory effect of JC were quercetin, licochalcone B, (+)-catechin, kaempferol, and emodin. Conclusions : This study provides the molecular targets and potential pathways of JC on inflammation. It can be used as a basic data for using JC for various inflammatory disease in traditional korean medicine clinic.

Theoretical Studies of the Gas-Phase Identity Nucleophilic Substitution Reactions of Cyclopentadienyl Halides

  • Lee, Ik-Choon;Li, Hong-Guang;Kim, Chang-Kon;Lee, Bon-Su;Kim, Chan-Kyung;Lee, Hai-Whang
    • Bulletin of the Korean Chemical Society
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    • 제24권5호
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    • pp.583-592
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    • 2003
  • The gas phase identity nucleophilic substitution reactions of halide anions (X = F, Cl, Br) with cyclopentadienyl halides (1) are investigated at the B3LYP/6-311+G**, MP2/6-311+G** and G2(+)MP2 levels involving five reaction pathways: σ-attack $S_N2$, β-$S_N$2'-syn, β-$S_N$2'-anti, γ-$S_N$2'-syn and γ-$S_N$2'-anti paths. In addition, the halide exchange reactions at the saturated analogue, cyclopentyl halides (2), and the monohapto circumambulatory halide rearrangements in 1 are also studied at the same three levels of theory. In the σ-attack $S_N2$ transition state for 1 weak positive charge develops in the ring with X = F while negative charge develops with X = Cl and Br leading to a higher energy barrier with X = F but to lower energy barriers with X = Cl and Br than for the corresponding reactions of 2. The π-attack β-$S_N$2' transition states are stabilized by the strong $n_C-{\pi}^{*}_{C=C}$ charge transfer interactions, whereas the π-attack γ-$S_N$2' transition states are stabilized by the strong $n_C-{\sigma}^{*}_{C-X}$ interactions. For all types of reaction paths, the energy barriers are lower with X = F than Cl and Br due to the greater bond energy gain in the partial C-X bond formation with X = F. The β-$S_N$2' paths are favored over the γ-$S_N$2' paths only with X = F and the reverse holds with X = Cl and Br. The σ-attack $S_N2$ reaction provides the lowest energy barrier with X = Cl and Br, but that with X = F is the highest energy barrier path. Activation energies for the circumambulatory rearrangement processes are much higher (by more than 18 kcal $mol^{-1}$) than those for the corresponding $S_N2$ reaction path. Overall the gas-phase halide exchanges are predicted to proceed by the σ-attack $S_N2$ path with X = Cl and Br but by the β-$S_N$2'-anti path with X = F. The barriers to the gas-phase halide exchanges increase in the order X = F < Br < Cl, which is the same as that found for the gas-phase identity methyl transfer reactions.

3D 바이오프린팅 사례로 본 다학제간 융복합 연구에 대한 소고 (A study on multidisciplinary and convergent research using the case of 3D bioprinting)

  • 박주안;정성준;마은정
    • 한국과학예술포럼
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    • 제30권
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    • pp.151-161
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    • 2017
  • 본 논문에서는 공학 분야에서 '공동연구' (collaboration) 과정을 연구 주제로 설정하고, 효과적인 협업의 형태 및 협업을 통해 생성되는 문화 또는 지식 창출의 가능성 및 함의에 대해 다룬다. '융합'에 대한 규범적 정의 및 행위 양식을 제안하는 방법을 취하지 않고, 융합의 한 형태로 공동연구를 선택하여 융합의 가능성을 탐색한다. 특히, 사회과학적 분석 방법을 빌어 3D 바이오프린팅 연구실에서 이뤄지고 있는 융합기술의 형성과정을 기술 및 분석하여, 공동연구를 통한 융합연구가 공학연구 문화 및 공학교육에 던지는 함의에 대해 논한다. 이를 위해 논문에서는 다음과 같은 질문을 던진다. 첫째, 학문하는 문화, 역사, 그리고 학문의 이론적 배경 및 방법이 전혀 다른 연구자들이 만나서 '공동연구'가 가능하며, 공동연구를 통해 유의미한 융합적 지식과 기술을 창출할 수 있을까? 둘째, 공동연구를 독려하고 촉진시키는 연구조직의 구성 조건 및 문화적 요소들은 무엇이 있을까? 셋째, 공동연구를 통해 소위 π자형 융합인재의 육성이 가능할까? 연구자들은 3D 바이오프린팅 사례를 통해 다음과 같은 결론을 내리고자 한다. 첫째, 정부 및 대학 차원에서의 재정적, 정책적 지원이 중요하며, 무엇보다 책임연구자의 융합연구에 대한 개방적, 능동적, 탄력적인 태도가 우선되어야 한다. 책임연구자는 학문적 배경이 다른 연구자들 사이에서 지적, 물적, 사회적, 인간적, 기술적 교류를 가능하게 하는 연구실 환경을 만드는 것이 중요하다. 둘째, 융합연구를 위해 해결해야 하는 도전적 난제들이 많음에도 생명과학과 프린팅 기술이 융합하여 3D 바이오프린팅이란 분야를 개척한 것처럼 이종적 학문 간의 의미있는 융합은 가능하다. 셋째, 융합연구의 장점 중의 하나는 4차 산업혁명 시대를 주도할 π형 인재 양성할 기회를 제공한다는 점이다.

Phospholipase Cγ의 생리적 기능과 질병과 연관된 돌연변이 (Physiological Roles of Phospholipase Cγ and Its Mutations in Human Disease)

  • 장현준;최장현;장종수
    • 생명과학회지
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    • 제30권9호
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    • pp.826-833
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    • 2020
  • Phospholipase C gamma (PLCγ)는 phosphatidylinositol을 가수분해하여 신호전달 과정에 참여하는 PLC의 주요한 isotype으로 γ-specific array의 특징적인 구조를 바탕으로 receptor tyrosine kinases 및 non-receptor tyrosine kinase 신호를 주로 매개한다. PLCγ1과 PLCγ2의 두 isozyme이 존재하며 다양한 세포에서 발현하여 cell proliferation, migration 및 differentiation 등 여러 세포작용을 조절하고 있다. 최근의 연구들에서 PLCγ 돌연변이가 cancer와 immune disease 및 brain disorder 등에 연관된다는 것이 밝혀지고 있으며 genetic model을 통해 PLCγ의 생리적·병리적 기능이 제시되었다. 본 리뷰에서는 최신의 연구 결과들을 바탕으로 PLCγ의 구조와 활성 조절 기전에 대해 기술하고 나아가 여러 질병의 발병과 진행에서 보고된 PLCγ의 돌연변이와 knockout 마우스를 활용한 연구 결과를 바탕으로 생리적·병리적 관점에서 PLCγ의 역할에 대해 고찰하였다.

가금 원료사료의 새로운 엽산 분석방법과 어린 육계의 엽산과 메티오닌의 요구량에 관한 연구 (Studies on the Folic Acid and Methionine Requirements for Young Broiler Chicks Including New Analytical Methods for Folic Acid in Poultry Feedstuffs)

  • 류경선;박강희;신원집
    • 한국가금학회지
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    • 제22권3호
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    • pp.179-188
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    • 1995
  • In Experiment 1, microbial assays were conducted on 57 feed ingredient samples to determine the content of total folic acid using Lactobacillus casei(ATCC 7469). Folic acid contents of feed samples pretreated with conjugase, ${\alpha}$-amylase, and a mixture of protease(Pronase)were corn, 09${\pm}$1.18($\pi$g${\pm}$SD); fish meal, 23.05${\pm}$1.27; milo, 29.34${\pm}$0.55; bakery meal, 25.80${\pm}$6.93; meat and bone meal, 56.76${\pm}$4.97; wheat middlings, 85.14${\pm}$2.56; and soybean meal, 193.97${\pm}$3.98. Experiments 2 and 3 were conducted to determine the effects of dietary supplemental folic acid and methionine on the performance of starting broiler chicks for 18 days. Four levels of dietary folic acid(0.24. 0.54,1.14 and 2.34mg/kg) and four levels of dietary methionine(0.45, 0.53,0.61, and 0.69%) were fed in a factorial design. The basal diet was based on corn, isolated soybean protein, meat and bone meal, and fish meal. It contained adequate amounts of all nutrients except methionine and folic acid in both experiments. Increased growth rate was observed in chicks fed the basal diet supplemented with either folic acid or methionine. Total dietary folic acid and methionine plus cysteine requirements for optimum growth were estimated to be 1.80 mg/kg and 0.89% in Experiment 2, and 1.47 mg/kg and 0.91% in Experiment 3, respectively. There were interactions between dietary folic acid and methionine on weight gain in both experiments. Chicks fed diets containing 2.34 mg folic acid /kg tended to display slow growth rate in both experiments. There was a significant linear feed conversion response to folic acid in Experiment 2, and a significant quadratic feed conversion resuonse to methionine in Experiment 3. There were both linear and quadratic liver folic acid responses to dietary folic acid in both experiments. There was no indication that dietary methionine had any effect on liver folic acid content. The incidence of tibial dyschondroplasia increased with increasing supplemental methionine, but were no significant differences detected at 5% level.

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Involvement of Lysosome Membrane Permeabilization and Reactive Oxygen Species Production in the Necrosis Induced by Chlamydia muridarum Infection in L929 Cells

  • Chen, Lixiang;Wang, Cong;Li, Shun;Yu, Xin;Liu, Xue;Ren, Rongrong;Liu, Wenwen;Zhou, Xiaojing;Zhang, Xiaonan;Zhou, Xiaohui
    • Journal of Microbiology and Biotechnology
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    • 제26권4호
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    • pp.790-798
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    • 2016
  • Chlamydiae, obligate intracellular bacteria, are associated with a variety of human diseases. The chlamydial life cycle undergoes a biphasic development: replicative reticulate bodies (RBs) phase and infectious elementary bodies (EBs) phase. At the end of the chlamydial intracellular life cycle, EBs have to be released to the surrounded cells. Therefore, the interactions between Chlamydiae and cell death pathways could greatly influence the outcomes of Chlamydia infection. However, the underlying molecular mechanisms remain elusive. Here, we investigated host cell death after Chlamydia infection in vitro, in L929 cells, and showed that Chlamydia infection induces cell necrosis, as detected by the propidium iodide (PI)-Annexin V double-staining flow-cytometric assay and Lactate dehydrogenase (LDH) release assay. The production of reactive oxygen species (ROS), an important factor in induction of necrosis, was increased after Chlamydia infection, and inhibition of ROS with specific pharmacological inhibitors, diphenylene iodonium (DPI) or butylated hydroxyanisole (BHA), led to significant suppression of necrosis. Interestingly, live-cell imaging revealed that Chlamydia infection induced lysosome membrane permeabilization (LMP). When an inhibitor upstream of LMP, CA-074-Me, was added to cells, the production of ROS was reduced with concomitant inhibition of necrosis. Taken together, our results indicate that Chlamydia infection elicits the production of ROS, which is dependent on LMP at least partially, followed by induction of host-cell necrosis. To our best knowledge, this is the first live-cell-imaging observation of LMP post Chlamydia infection and report on the link of LMP to ROS to necrosis during Chlamydia infection.

한국형 중풍 변증 표준안 - II와 한열허실 변증지표의 연관성 연구 (Study on the Relationship between Korean Standard of Pattern Identification (II) and Pattern Identification of Cold-Heat and Deficiency-Excess)

  • 김소연;이정섭;오달석;강병갑;고미미;김정철;권세혁;방옥선
    • 동의생리병리학회지
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    • 제24권1호
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    • pp.15-21
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    • 2010
  • Previously standardization study for identifying 5 types of pattern identification of stroke patients has been performed and the Korean standard of pattern identification (II) was developed. In the present study we investigated the interactions between total indices designated by the Korean standard of pattern identification(KSPI II) and indices for PI of Cold-Heat and Deficiency-Excess. Indicators for Cold-Heat and Deficiency-Excess are isolated from 58 indices through the survey of oriental medicine doctors and their relationship with KSPI-II indices was analyzed by corresponding analysis method using data of 1581 stroke patients. Means and standard deviations indicated that 2 Cold indices, 14 Heat indices, 12 Deficiency indices, and 5 Excess indices were included for Cold-Heat and Deficiency-Excess pattern identification. The results of corresponding analysis shows the relationship of 57 indices and 4 types of pattern identification (excluding 1 index and 1 pattern among 58 indices and 5 patterns) using the cross-tabulation which was obtained from the clinical data. Most of Cold and Heat index were divided to dimension 1(inertia 51.9%) obtained from the result of corresponding analysis. Deficiency and Excess index were partially associated with dimension 2(inertia 31.7%). These data suggest that pattern identification of Cold-Heat plays an role in the standardization of pattern identification in stroke, although further studies are required by various trials such as analysis of surveys and clinical data.

Putative multiple reaction monitoring strategy for the comparative pharmacokinetics of postoral administration Renshen-Yuanzhi compatibility through liquid chromatography-tandem mass spectrometry

  • Sun, Yufei;Feng, Guifang;Zheng, Yan;Liu, Shu;Zhang, Yan;Pi, Zifeng;Song, Fengrui;Liu, Zhiqiang
    • Journal of Ginseng Research
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    • 제44권1호
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    • pp.105-114
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    • 2020
  • Background: Exploring the pharmacokinetic (PK) changes of various active components of single herbs and their combinations is necessary to elucidate the compatibility mechanism. However, the lack of chemical standards and low concentrations of multiple active ingredients in the biological matrix restrict PK studies. Methods: A putative multiple reaction monitoring strategy based on liquid chromatography coupled with mass spectrometry (LC-MS) was developed to extend the PK scopes of quantification without resorting to the use of chemical standards. First, the compounds studied, including components with available reference standard (ARS) and components lacking reference standard (LRS), were preclassified to several groups according to their chemical structures. Herb decoctions were then subjected to ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis with appropriate collision energy (CE) in MS2 mode. Finally, multiple reaction monitoring transitions transformed from MS2 of ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were used for ultrahigh-performance liquid chromatography coupled with triple quadrupole mass spectrometry to obtain the mass responses of LRS components. LRS components quantification was further performed by developing an assistive group-dependent semiquantitative method. Results: The developed method was exemplified by the comparative PK process of single herbs Radix Ginseng (RG), Radix Polygala (RP), and their combinations (RG-RP). Significant changes in PK parameters were observed before and after combination. Conclusion: Results indicated that Traditional Chinese Medicine combinations can produce synergistic effects and diminish possible toxic effects, thereby reflecting the advantages of compatibility. The proposed strategy can solve the quantitative problem of LRS and extend the scopes of PK studies.