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  1. Article: Current status of structure-based drug repurposing against COVID-19 by targeting SARS-CoV-2 proteins.

    Hijikata, Atsushi / Shionyu, Clara / Nakae, Setsu / Shionyu, Masafumi / Ota, Motonori / Kanaya, Shigehiko / Shirai, Tsuyoshi

    Biophysics and physicobiology

    2021  Volume 18, Page(s) 226–240

    Abstract: More than one and half years have passed, as of August 2021, since the COVID-19 caused by the novel coronavirus named SARS-CoV-2 emerged in 2019. While the recent success of vaccine developments likely reduces the severe cases, there is still a strong ... ...

    Abstract More than one and half years have passed, as of August 2021, since the COVID-19 caused by the novel coronavirus named SARS-CoV-2 emerged in 2019. While the recent success of vaccine developments likely reduces the severe cases, there is still a strong requirement of safety and effective therapeutic drugs for overcoming the unprecedented situation. Here we review the recent progress and the status of the drug discovery against COVID-19 with emphasizing a structure-based perspective. Structural data regarding the SARS-CoV-2 proteome has been rapidly accumulated in the Protein Data Bank, and up to 68% of the total amino acid residues encoded in the genome were covered by the structural data. Despite a global effort of
    Language English
    Publishing date 2021-10-05
    Publishing country Japan
    Document type Journal Article
    ISSN 2189-4779
    ISSN 2189-4779
    DOI 10.2142/biophysico.bppb-v18.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Stochastic ERK activation induced by noise and cell-to-cell propagation regulates cell density-dependent proliferation.

    Aoki, Kazuhiro / Kumagai, Yuka / Sakurai, Atsuro / Komatsu, Naoki / Fujita, Yoshihisa / Shionyu, Clara / Matsuda, Michiyuki

    Molecular cell

    2013  Volume 52, Issue 4, Page(s) 529–540

    Abstract: The extracellular signal-regulated kinase (ERK) plays a central role in the signaling cascades of cell growth. Here, we show that stochastic ERK activity pulses regulate cell proliferation rates in a cell density-dependent manner. A fluorescence ... ...

    Abstract The extracellular signal-regulated kinase (ERK) plays a central role in the signaling cascades of cell growth. Here, we show that stochastic ERK activity pulses regulate cell proliferation rates in a cell density-dependent manner. A fluorescence resonance energy transfer (FRET) biosensor revealed that stochastic ERK activity pulses fired spontaneously or propagated from adjacent cells. Frequency, but not amplitude, of ERK activity pulses exhibited a bell-shaped response to the cell density and correlated with cell proliferation rates. Consistently, synthetic ERK activity pulses generated by a light-switchable CRaf protein accelerated cell proliferation. A mathematical model clarified that 80% and 20% of ERK activity pulses are generated by the noise and cell-to-cell propagation, respectively. Finally, RNA sequencing analysis of cells subjected to the synthetic ERK activity pulses suggested the involvement of serum responsive factor (SRF) transcription factors in the gene expression driven by the ERK activity pulses.
    MeSH term(s) Algorithms ; Animals ; Benzamides/pharmacology ; Cell Communication ; Cell Count ; Cell Line ; Cell Proliferation ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation ; Humans ; Imidazoles/pharmacology ; Kinetics ; MAP Kinase Signaling System ; Models, Biological ; Promoter Regions, Genetic ; Rats ; Sequence Analysis, RNA ; Stochastic Processes ; Time-Lapse Imaging ; raf Kinases/antagonists & inhibitors ; raf Kinases/metabolism
    Chemical Substances 2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide ; Benzamides ; Imidazoles ; SB-590885 ; raf Kinases (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2013-11-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2013.09.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5055: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Fluctuation of Rac1 activity is associated with the phenotypic and transcriptional heterogeneity of glioma cells.

    Yukinaga, Hiroko / Shionyu, Clara / Hirata, Eishu / Ui-Tei, Kumiko / Nagashima, Takeshi / Kondo, Shinji / Okada-Hatakeyama, Mariko / Naoki, Honda / Matsuda, Michiyuki

    Journal of cell science

    2014  Volume 127, Issue Pt 8, Page(s) 1805–1815

    Abstract: Phenotypic heterogeneity of cancer cells is caused not only by genetic and epigenetic alterations but also by stochastic variation of intracellular signaling molecules. Using cells that stably express Förster resonance energy transfer (FRET) biosensors, ... ...

    Abstract Phenotypic heterogeneity of cancer cells is caused not only by genetic and epigenetic alterations but also by stochastic variation of intracellular signaling molecules. Using cells that stably express Förster resonance energy transfer (FRET) biosensors, we show here a correlation between a temporal fluctuation in the activity of Rac1 and the invasive properties of C6 glioma cells. By using long-term time-lapse imaging, we found that Rac1 activity in C6 glioma cells fluctuated over a timescale that was substantially longer than that of the replication cycle. Because the relative level of Rac1 activity in each cell was unaffected by a suspension-adhesion procedure, we were able to sort C6 glioma cells according to the levels of Rac1 activity, yielding Rac1(high) and Rac1(low) cells. The Rac1(high) cells invaded more efficiently than did Rac1(low) cells in a Matrigel invasion assay. We assessed the transcriptional profiles of Rac1(high) and Rac1(low) cells and performed gene ontology analysis. Among the 14 genes that were most associated with the term 'membrane' (membrane-related genes) in Rac1(high) cells, we identified four genes that were associated with glioma invasion and Rac1 activity by using siRNA knockdown experiments. Among the transcription factors upregulated in Rac1(high) cells, Egr2 was found to positively regulate expression of the four membrane-related invasion-associated genes. The identified signaling network might cause the fluctuations in Rac1 activity and the heterogeneity in the invasive capacity of glioma cells.
    MeSH term(s) Animals ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Glioma/metabolism ; Glioma/pathology ; Neoplasm Invasiveness ; Phenotype ; Protein Transport ; Rats ; Signal Transduction ; Transcription, Genetic ; Transcriptome ; Up-Regulation ; rac1 GTP-Binding Protein/metabolism
    Chemical Substances Rac1 protein, rat (EC 3.6.1.-) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
    Language English
    Publishing date 2014-04-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.139733
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1200: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 14: Show issues

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  4. Article: Stochastic ERK Activation Induced by Noise and Cell-to-Cell Propagation Regulates Cell Density-Dependent Proliferation

    Aoki, Kazuhiro / Kumagai, Yuka / Sakurai, Atsuro / Komatsu, Naoki / Fujita, Yoshihisa / Shionyu, Clara / Matsuda, Michiyuki

    Molecular cell

    Volume v. 52,, Issue no. 4

    Abstract: The extracellular signal-regulated kinase (ERK) plays a central role in the signaling cascades of cell growth. Here, we show that stochastic ERK activity pulses regulate cell proliferation rates in a cell density-dependent manner. A fluorescence ... ...

    Abstract The extracellular signal-regulated kinase (ERK) plays a central role in the signaling cascades of cell growth. Here, we show that stochastic ERK activity pulses regulate cell proliferation rates in a cell density-dependent manner. A fluorescence resonance energy transfer (FRET) biosensor revealed that stochastic ERK activity pulses fired spontaneously or propagated from adjacent cells. Frequency, but not amplitude, of ERK activity pulses exhibited a bell-shaped response to the cell density and correlated with cell proliferation rates. Consistently, synthetic ERK activity pulses generated by a light-switchable CRaf protein accelerated cell proliferation. A mathematical model clarified that 80% and 20% of ERK activity pulses are generated by the noise and cell-to-cell propagation, respectively. Finally, RNA sequencing analysis of cells subjected to the synthetic ERK activity pulses suggested the involvement of serum responsive factor (SRF) transcription factors in the gene expression driven by the ERK activity pulses.
    Keywords blood serum ; biosensors ; cells ; energy transfer ; transcription factors ; mathematical models ; mitogen-activated protein kinase ; cell proliferation ; RNA ; fluorescence ; sequence analysis ; gene expression ; cell growth
    Language English
    Document type Article
    ISSN 1097-2765
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

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