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eRF1aMC and $Mg^{2+}$ Dependent Structure Switch of GTP Binding to eRF3 in Euplotes octocarinatus

  • Song, Li;Jia, Yu-Xin;Zhu, Wen-Si;Chai, Bao-Feng;Liang, Ai-Hua
    • Journal of Microbiology and Biotechnology
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    • v.22 no.2
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    • pp.176-183
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    • 2012
  • Eukaryotic translation termination is governed by eRF1 and eRF3. eRF1 recognizes the stop codons and then hydrolyzes peptidyl-tRNA. eRF3, which facilitates the termination process, belongs to the GTPase superfamily. In this study, the effect of the MC domain of eRF1a (eRF1aMC) on the GTPase activity of eRF3 was analyzed using fluorescence spectra and high-performance liquid chromatography. The results indicated eRF1aMC promotes the GTPase activity of eRF3, which is similar to the role of eRF1a. Furthermore, the increased affinity of eRF3 for GTP induced by eRF1aMC was dependent on the concentration of $Mg^{2+}$. Changes in the secondary structure of eRF3C after binding GTP/GDP were detected by CD spectroscopy. The results revealed changes of conformation during formation of the eRF3C GTP complex that were detected in the presence of eRF1a or eRF1aMC. The conformations of the eRF3C eRF1a GTP and eRF3C eRF1aMC GTP complexes were further altered upon the addition of $Mg^{2+}$. By contrast, there was no change in the conformation of GTP bound to free eRF3C or the eRF3C eRF1aN complex. These results suggest that alterations in the conformation of GTP bound to eRF3 is dependent on eRF1a and $Mg^{2+}$, whereas the MC domain of eRF1a is responsible for the change in the conformation of GTP bound to eRF3 in Euplotes octocarinatus.

20(S)-ginsenoside Rh2 induces caspase-dependent promyelocytic leukemia-retinoic acid receptor A degradation in NB4 cells via Akt/Bax/caspase9 and TNF-α/caspase8 signaling cascades

  • Zhu, Sirui;Liu, Xiaoli;Xue, Mei;Li, Yu;Cai, Danhong;Wang, Shijun;Zhang, Liang
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.295-304
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    • 2021
  • Background: Acute promyelocytic leukemia (APL) is a hematopoietic malignancy driven by promyelocytic leukemia-retinoic acid receptor A (PML-RARA) fusion gene. The therapeutic drugs currently used to treat APL have adverse effects. 20(S)-ginsenoside Rh2 (GRh2) is an anticancer medicine with high effectiveness and low toxicity. However, the underlying anticancer mechanisms of GRh2-induced PML-RARA degradation and apoptosis in human APL cell line (NB4 cells) remain unclear. Methods: Apoptosis-related indicators and PML-RARA expression were determined to investigate the effect of GRh2 on NB4 cells. Z-VAD-FMK, LY294002, and C 87, as inhibitors of caspase, and the phosphatidylinositol 3-kinase (PI3K) and tumor necrosis factor-α (TNF-α) pathways were used to clarify the relationship between GRh2-induced apoptosis and PML-RARA degradation. Results: GRh2 dose- and time-dependently decreased NB4 cell viability. GRh2-induced apoptosis, cell cycle arrest, and caspase3, caspase8, and caspase9 activation in NB4 cells after a 12-hour treatment. GRh2-induced apoptosis in NB4 cells was accompanied by massive production of reactive oxygen species, mitochondrial damage and upregulated Bax/Bcl-2 expression. GRh2 also induced PML/PML-RARA degradation, PML nuclear bodies formation, and activation of the downstream p53 pathway in NB4 cells. Z-VAD-FMK inhibited caspase activation and significantly reversed GRh2-induced apoptosis and PML-RARA degradation. GRh2 also upregulated TNF-α expression and inhibited Akt phosphorylation. LY294002, an inhibitor of the PI3K pathway, enhanced the antitumor effects of GRh2, and C 87, an inhibitor of the TNF-α pathway, reversed NB4 cell viability, and GRh2-mediated apoptosis in a caspase-8-dependent manner. Conclusion: GRh2 induced caspase-dependent PML-RARA degradation and apoptosis in NB4 cells via the Akt/Bax/caspase9 and TNF-α/caspase8 pathways.

An inhibitory role of NEK6 in TGFβ/Smad signaling pathway

  • Zuo, Jie;Ma, Haijie;Cai, Hao;Wu, Yanhua;Jiang, Wei;Yu, Long
    • BMB Reports
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    • v.48 no.8
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    • pp.473-478
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    • 2015
  • The NEK6 (NIMA-related kinases 6) is reported to play po-tential roles in tumorigenesis. Although it is suggested to function in several cellular pathways, the underlying mechanism in tumorigenesis is still largely unknown. In the present study, we discovered interaction of NEK6 with Smad4, a key member of transforming growth factor beta (TGFβ) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGFβ-mediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGFβ. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGFβ function. Moreover, we identified that NEK6 could be regulated by TGFβ and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGFβ/Smad pathway and tum-origenesis. [BMB Reports 2015; 48(8): 473-478]

Magnetic and Structural Properties of MnBi1-xTix Alloys

  • Zhang, Suyin;Zhang, Pengyue;Jiang, HuanChang;Shi, Yaojun;Yu, Nengjun;Ge, Hongliang
    • Journal of Magnetics
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    • v.19 no.3
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    • pp.205-209
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    • 2014
  • $MnBi_{1-x}Ti_x$ (x = 0, 0.4, 0.7, 1) alloys were prepared by arc-melting, followed by heat treatment. X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) were used to measure and investigate the phase structure and magnetic properties. The temperature dependent magnetization curves indicate that the phase transitions between LTP and HTP MnBi occur with heating or cooling in $MnBi_{1-x}Ti_x$ ($x{\leq}0.7$) samples. However, MnTi samples are in $Mn_2Ti$ single-phase, with very low magnetic properties. Furthermore, the coercivity exhibits a positive temperature coefficient. The results show that the optimal content of Ti for the coercivity of $MnBi_{1-x}Ti_x$ alloy is x = 0.4. For MnBi sample, the coercivity reaches a maximum value of 1.13 T at 550 K. However, the remanence and energy product show apparent decrease with the addition of Ti in $MnBi_{1-x}Ti_x$ alloys.

Interactions among Measles Virus Hemagglutinin, Fusion Protein and Cell Receptor Signaling Lymphocyte Activation Molecule (SLAM) Indicating a New Fusion-trimer Model

  • Zhang, Peng;Li, Lingyun;Hu, Chunlin;Xu, Qin;Liu, Xin;Qi, Yipeng
    • BMB Reports
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    • v.38 no.4
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    • pp.373-380
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    • 2005
  • For measles viruses, fusion on the cell membrane is an important initial step in the entry into the infected cells. The recent research indicated that hemagglutinin firstly leads the conformational changes in the fusion protein then co-mediates the membrane fusion. In the work, we use the co-immunoprecipitation and pull-down techniques to identify the interactions among fusion protein, hemagglutinin and signaling lymphocyte activation molecule (SLAM), which reveal that the three proteins can form a functional complex to mediate the SLAM-dependent fusion. Moreover, under the confocal microscope, fusion protein and hemagglutinin protein can show the cocapping mediated by the SLAM. So fusion protein not only is involved in the fusion but also might directly interact with the SLAM to be a new fusion-trimer model, which might account for the infection mechanism of measles virus.

Anti-tumor Effects and Apoptosis Induction by Realgar Bioleaching Solution in Sarcoma-180 Cells in Vitro and Transplanted Tumors in Mice in Vivo

  • Xie, Qin-Jian;Cao, Xin-Li;Bai, Lu;Wu, Zheng-Rong;Ma, Ying-Ping;Li, Hong-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2883-2888
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    • 2014
  • Background: Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. Materials and Methods: Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. Results: The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumor.s Conclusions: RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment.

HOCl Oxidation-modified CT26 Cell Vaccine Inhibits Colon Tumor Growth in a Mouse Model

  • Zhou, Rui;Huang, Wen-Jun;Ma, Cong;Zhou, Yan;Yao, Yu-Qin;Wang, Yu-Xi;Gou, Lan-Tu;Yi, Chen;Yang, Jin-Liang
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4037-4043
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    • 2012
  • Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.

A Review of Sleep-Dependent Motor Learning (수면 의존성 운동 학습에 대한 고찰)

  • Lee, Myoung-Hee;Lee, Sang-Yeol;Park, Min-Chull;Bae, Sung-Soo
    • PNF and Movement
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    • v.6 no.3
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    • pp.19-28
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    • 2008
  • Purpose : The objective of this study was to determine efficacy of sleep-dependent motor learning. Methods : This is a literature study with books and internet. We searched the PubMed, Science Direct, KISS and DBpia. Key words were Sleep-dependent, motor learning, RAM and LTP. Results : Procedural memory, like declarative memory, undergoes a slow, time-dependent period of consolidation. A process has recently been described wherein performance on some procedural task improves with the mere passage of time and has been termed "enhancement". Some studies have reported that the consolidation/enhancement of perceptual and motor skill is dependent on sleep. Specially, rapid-eye-movement(REM) sleep seems to benefit procedural aspects of memory. Conclusion : Motor learning is very important for CNS injury patients. And also distribution of practice sessions is important because REM sleep is to benefit procedural aspects of memory consolidation.

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Numerical analysis of embankment primary consolidation with porosity-dependent and strain-dependent coefficient of permeability

  • Balic, Anis;Hadzalic, Emina;Dolarevic, Samir
    • Coupled systems mechanics
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    • v.11 no.2
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    • pp.93-106
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    • 2022
  • The total embankment settlement consists of three stages: the initial settlement, the primary consolidation settlement, and the secondary consolidation settlement. The total embankment settlement is largely controlled by the primary consolidation settlement, which is usually computed with numerical models that implement Biot's theory of consolidation. The key parameter that affects the primary consolidation time is the coefficient of permeability. Due to the complex stress and strain states in the foundation soil under the embankment, to be able to predict the consolidation time more precisely, aside from porosity-dependency, the strain-dependency of the coefficient of permeability should be also taken into account in numerical analyses. In this paper, we propose a two-dimensional plane strain numerical model of embankment primary consolidation, which implements Biot's theory of consolidation with both porosity-dependent and strain-dependent coefficient of permeability. We perform several numerical simulations. First, we demonstrate the influence of the strain-dependent coefficient of permeability on the computed results. Next, we validate our numerical model by comparing computed results against in-situ measurements for two road embankments: one near the city of Saga, and the other near the city of Boston. Finally, we give our concluding remarks.

New Robust $H_{\infty}$ Performance Condition for Uncertain Discrete-Time Systems

  • Zhai, Guisheng;Lin, Hai;Kim, Young-Bok
    • 제어로봇시스템학회:학술대회논문집
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    • 2003.10a
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    • pp.322-326
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    • 2003
  • In this paper, we establish a new robust $H_{\infty}$ performance condition for uncertain discrete-time systems with convex polytopic uncertainties. We express the condition as a set of linear matrix inequalities (LMIs), which are used to check stability and $H_{\infty}$ disturbance attenuation level by a parameter-dependent Lyapunov matrix. We show that the new condition provides less conservative result than the existing ones which use single Lyapunov matrix. We also show that the robust $H_{\infty}$ state feedback design problem for such uncertain discrete-time systems can be easily dealt with using the approach. The key point in this paper is to propose a kind of decoupling between the Lyapunov matrix and the system matrices in the parameter-dependent matrix inequality by introducing one new matrix variable.

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