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  1. Article ; Online: Interaction between Gtr2p and ribosomal Rps31p affects the incorporation of Rps31p into ribosomes of Saccharomyces cerevisiae.

    Sekiguchi, Takeshi / Ishii, Takashi / Funakoshi, Minoru / Kobayashi, Hideki / Furuno, Nobuaki

    Biochemical and biophysical research communications

    2024  Volume 699, Page(s) 149499

    Abstract: In yeast, ras-like small G proteins, Gtr1p and Gtr2p, form heterodimers that affect cell division, detect amino acids, and regulate the activity of TORC1, a protein complex that integrates various signals, including those related to nutrient availability, ...

    Abstract In yeast, ras-like small G proteins, Gtr1p and Gtr2p, form heterodimers that affect cell division, detect amino acids, and regulate the activity of TORC1, a protein complex that integrates various signals, including those related to nutrient availability, growth factors, and stress signals. To explore novel roles of Gtr2p, yeast two-hybrid screening was performed using gtr2S23Np, an active form of Gtr2p, which identified Rps31p and Rpl12p as Gtr2p-interacting proteins. In the present study, we found that Gtr2p, but not Gtr1p, interacts with Rps31p, a 40S ribosomal subunit, and a component of the ubiquitin fusion protein Ubi3p, which is essential for the initiation and elongation of translation. In yeast cells expressing gtr2Q66Lp, an inactive form of Gtr2p, the interaction between Rps31p and gtr2Q66Lp, as well as the level of exogenous expression of Rps31p, was reduced. However, the level of exogenous expression of Rpl12p was unaffected. Introducing a mutation in ubiquitin target lysine residues to arginine (rps31-K5R) restored the level of exogenously expressed Rps31p and rescued the rapamycin and caffeine sensitivity of gtr2Q66L cells. Sucrose density gradient centrifugation of yeast cell lysate expressing Rps31p and gtr2Q66Lp revealed that exogenously expressed Rps31p was poorly incorporated, whereas rps31-K5Rp was efficiently incorporated, into ribosomes. These results suggest that Gtr2p influences incorporation of Rps31p into ribosomes and contributes to drug resistance through its interaction with Rps31p.
    MeSH term(s) Monomeric GTP-Binding Proteins/metabolism ; Ribosomal Proteins/genetics ; Ribosomal Proteins/metabolism ; Ribosomes/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Ubiquitins/metabolism
    Chemical Substances GTR2 protein, S cerevisiae ; Monomeric GTP-Binding Proteins (EC 3.6.5.2) ; Ribosomal Proteins ; Saccharomyces cerevisiae Proteins ; Ubiquitins ; Rps31 protein, S cerevisiae
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2024.149499
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reduction of HIF-1α/PD-L1 by Catalytic Topoisomerase Inhibitor Induces Cell Death Through Caspase Activation in Cancer Cells Under Hypoxia.

    Miyata, Shohei / Ishii, Takashi / Kitanaka, Susumu

    Anticancer research

    2023  Volume 44, Issue 1, Page(s) 49–59

    Abstract: Background/aim: Under severe hypoxia, cellular apoptosis is induced through hypoxia-inducible factor 1, alpha subunit (HIF-1α)-dependent P53 accumulation and P53 phosphorylation via ataxia telangiectasia mutated and ataxia telangiectasia and RAD3- ... ...

    Abstract Background/aim: Under severe hypoxia, cellular apoptosis is induced through hypoxia-inducible factor 1, alpha subunit (HIF-1α)-dependent P53 accumulation and P53 phosphorylation via ataxia telangiectasia mutated and ataxia telangiectasia and RAD3-related (ATR) activation via replication stress-induced DNA damage response (DDR) activation. We previously demonstrated that the topoisomerase I catalytic inhibitor, 3-O-(2'E,4'Z-decadienoyl)-20-O-acetylingenol (3EZ,20Ac-ingenol), induced apoptosis in Jeko-1 and Panc-1 cells, both of which show cyclin D1 overexpression. After progression to the S phase facilitated by nuclear cyclin D1, an intra S phase checkpoint was induced in the presence of 3EZ,20Ac-ingenol, by ATR activation in response to replication stress-induced DDR.
    Materials and methods: In this study, we examined whether 3-O-(2'E,4'E-decadienoyl)-20-O-acetylingenol (3EE,20Ac-ingenol) might induce a higher degree of P53 phosphorylation and additional HIF-1α and P53 accumulation in response to replication stress-induced DDR activation under hypoxic conditions than under normoxic conditions, by controlling ATR activation.
    Results: In the Panc-1 cells, 3EE,20Ac-ingenol induced P53 activation and HIF-1α-dependent P53 accumulation through cooperative ATR activation via hypoxia-induced DDR activation. Jeko-1 cells showed slight HIF-1α accumulation under hypoxia, but HIF-1α-dependent 53 accumulation was not observed in the presence of 3EE,20Ac-ingenol, so that the cells remained resistant to hypoxia.
    Conclusion: 3EE,20Ac-ingenol induces an intricate interplay between P53 and HIF-1α accumulation via ATR activation that results in a high P53 accumulation, which promoted transient expression and early disappearance of HIF-1α, accelerating cell death. Strong P53 accumulation and consequent phosphatase and tensin homolog deleted on chromosome 10 activation in Panc-1 cells also reduced HIF-1α accumulation and programmed death-ligand 1 expression, which resulted in intense apoptosis.
    MeSH term(s) Humans ; Apoptosis ; B7-H1 Antigen/metabolism ; Caspases/metabolism ; Cell Hypoxia ; Cyclin D1/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Neoplasms ; Topoisomerase I Inhibitors/pharmacology ; Tumor Suppressor Protein p53/metabolism ; Cell Line, Tumor
    Chemical Substances B7-H1 Antigen ; Caspases (EC 3.4.22.-) ; Cyclin D1 (136601-57-5) ; Hypoxia-Inducible Factor 1, alpha Subunit ; ingenol (IC77UZI9G8) ; Topoisomerase I Inhibitors ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2023-12-31
    Publishing country Greece
    Document type Journal Article
    ZDB-ID 604549-2
    ISSN 1791-7530 ; 0250-7005
    ISSN (online) 1791-7530
    ISSN 0250-7005
    DOI 10.21873/anticanres.16787
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Quantitative evaluation model of variable diagnosis for chest X-ray images using deep learning.

    Nakagawa, Shota / Ono, Naoaki / Hakamata, Yukichika / Ishii, Takashi / Saito, Akira / Yanagimoto, Shintaro / Kanaya, Shigehiko

    PLOS digital health

    2024  Volume 3, Issue 3, Page(s) e0000460

    Abstract: The purpose of this study is to demonstrate the use of a deep learning model in quantitatively evaluating clinical findings typically subject to uncertain evaluations by physicians, using binary test results based on routine protocols. A chest X-ray is ... ...

    Abstract The purpose of this study is to demonstrate the use of a deep learning model in quantitatively evaluating clinical findings typically subject to uncertain evaluations by physicians, using binary test results based on routine protocols. A chest X-ray is the most commonly used diagnostic tool for the detection of a wide range of diseases and is generally performed as a part of regular medical checkups. However, when it comes to findings that can be classified as within the normal range but are not considered disease-related, the thresholds of physicians' findings can vary to some extent, therefore it is necessary to define a new evaluation method and quantify it. The implementation of such methods is difficult and expensive in terms of time and labor. In this study, a total of 83,005 chest X-ray images were used to diagnose the common findings of pleural thickening and scoliosis. A novel method for quantitatively evaluating the probability that a physician would judge the images to have these findings was established. The proposed method successfully quantified the variation in physicians' findings using a deep learning model trained only on binary annotation data. It was also demonstrated that the developed method could be applied to both transfer learning using convolutional neural networks for general image analysis and a newly learned deep learning model based on vector quantization variational autoencoders with high correlations ranging from 0.89 to 0.97.
    Language English
    Publishing date 2024-03-15
    Publishing country United States
    Document type Journal Article
    ISSN 2767-3170
    ISSN (online) 2767-3170
    DOI 10.1371/journal.pdig.0000460
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: JNK inhibition enhances cell-cell adhesion impaired by desmoglein 3 gene disruption in keratinocytes.

    Ogawa, Shuhei / Ishii, Takashi / Otani, Takahito / Inai, Yuko / Matsuura, Takashi / Inai, Tetsuichiro

    Histochemistry and cell biology

    2024  Volume 161, Issue 4, Page(s) 345–357

    Abstract: ... c-Jun ... ...

    Abstract c-Jun NH
    MeSH term(s) Cell Adhesion/genetics ; Desmoglein 3/genetics ; Desmoglein 3/metabolism ; Keratinocytes/metabolism ; MAP Kinase Signaling System
    Chemical Substances Desmoglein 3
    Language English
    Publishing date 2024-01-16
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1222930-1
    ISSN 1432-119X ; 0301-5564 ; 0948-6143
    ISSN (online) 1432-119X
    ISSN 0301-5564 ; 0948-6143
    DOI 10.1007/s00418-023-02264-8
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  5. Article: Cultivation of cos lettuce using blue LED and quantum dot wavelength conversion sheets

    Jishi, Tomohiro / Ishii, Takashi / Shoji, Kazuhiro

    Scientia horticulturae. 2022 Mar. 15, v. 295

    2022  

    Abstract: The aims of this study were to cultivate cos lettuce (Lactuca sativa L. cv. Cos Lettuce) using quantum dot (QD) sheets for wave conversion and to clarify the advantages and disadvantages of this technique for plant cultivation with artificial lighting. ... ...

    Abstract The aims of this study were to cultivate cos lettuce (Lactuca sativa L. cv. Cos Lettuce) using quantum dot (QD) sheets for wave conversion and to clarify the advantages and disadvantages of this technique for plant cultivation with artificial lighting. Blue LED light was wavelength-converted to green (G-QD) or red (R-QD) light by QD sheets and used for cultivating cos lettuce. Then, lighting with spectral photon flux density distributions similar to those of G-QD and R-QD was designed using green or red LED and blue LED (G-LED and R-LED), respectively, and used for cultivating cos lettuce. Plant growth at 14 days after treatment revealed that the shoot fresh weight was greater under G-QD compared with G-LED, perhaps because the amount of integrated light reception was greater in G-QD owing to the difference in the photosynthetic photon flux density's spatial distribution. Plants showed similar growth levels and morphologies under R-QD and R-LED lights. Plant growth is affected by the light environment, such as spectral photon flux density distributions and its vector field, regardless of the light source. However, the prototype QD sheets used in the present study had low conversion efficiencies and wide directivity angles. If QD products are developed that utilize the advantages of high monochromaticity and long life for plant cultivation at low costs, then they may become widely used.
    Keywords Lactuca sativa var. longifolia ; lighting ; photons ; photosynthesis ; plant growth ; prototypes ; quantum dots ; wavelengths
    Language English
    Dates of publication 2022-0315
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 185557-8
    ISSN 0304-4238
    ISSN 0304-4238
    DOI 10.1016/j.scienta.2021.110772
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Glucocorticoid-induced TNF receptor family-related protein functions as a costimulatory molecule for murine eosinophils.

    Narita, Tomoya / Murakami, Yusuke / Ishii, Takashi / Muroi, Masashi / Yamashita, Naomi

    Journal of leukocyte biology

    2023  Volume 115, Issue 4, Page(s) 771–779

    Abstract: Eosinophils are typical effector cells associated with type 2 immune responses and play key roles in the pathogenesis of allergic diseases. These cells are activated by various stimuli, such as cytokines, chemokines, and growth factors, but the ... ...

    Abstract Eosinophils are typical effector cells associated with type 2 immune responses and play key roles in the pathogenesis of allergic diseases. These cells are activated by various stimuli, such as cytokines, chemokines, and growth factors, but the regulatory mechanisms of eosinophil effector functions remain unclear. Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR), a transmembrane protein belonging to the tumor necrosis factor (TNF) receptor superfamily, is a well-known regulatory molecule for T cell activation. Here, we show that GITR is also constitutively expressed on eosinophils and functions as a costimulatory molecule for these cells. Although degranulation was unaffected by GITR engagement of murine bone marrow-derived eosinophils, secretion of inflammatory cytokines such as interleukin (IL)-4, IL-6, and IL-13 from IL-33-activated bone marrow-derived eosinophils was augmented by anti-mouse GITR agonistic antibody (DTA-1). In conclusion, our results provide a new regulatory pathway of cytokine secretion from eosinophils in which GITR functions as a costimulatory molecule.
    MeSH term(s) Animals ; Mice ; Glucocorticoids ; Eosinophils/metabolism ; Glucocorticoid-Induced TNFR-Related Protein ; Receptors, Tumor Necrosis Factor ; Cytokines/metabolism ; Tumor Necrosis Factors ; Transcription Factors
    Chemical Substances Glucocorticoids ; Glucocorticoid-Induced TNFR-Related Protein ; Receptors, Tumor Necrosis Factor ; Cytokines ; Tumor Necrosis Factors ; Transcription Factors
    Language English
    Publishing date 2023-12-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1093/jleuko/qiad166
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  7. Article ; Online: Strong eigenstate thermalization within a generalized shell in noninteracting integrable systems.

    Ishii, Takashi / Mori, Takashi

    Physical review. E

    2019  Volume 100, Issue 1-1, Page(s) 12139

    Abstract: Integrable systems do not obey the strong eigenstate thermalization hypothesis (ETH), which has been proposed as a mechanism of thermalization in isolated quantum systems. It has been suggested that an integrable system reaches a steady state described ... ...

    Abstract Integrable systems do not obey the strong eigenstate thermalization hypothesis (ETH), which has been proposed as a mechanism of thermalization in isolated quantum systems. It has been suggested that an integrable system reaches a steady state described by a generalized Gibbs ensemble (GGE) instead of thermal equilibrium. We prove that a generalized version of the strong ETH holds for noninteracting integrable systems with translation invariance. Our generalized ETH states that any pair of energy eigenstates with similar values of local conserved quantities looks similar with respect to local observables, such as local correlations. This result tells us that an integrable system relaxes to a GGE for any initial state that has subextensive fluctuations of macroscopic local conserved quantities. Contrary to the previous derivations of the GGE, it is not necessary to assume the cluster decomposition property for an initial state.
    Language English
    Publishing date 2019-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2844562-4
    ISSN 2470-0053 ; 2470-0045
    ISSN (online) 2470-0053
    ISSN 2470-0045
    DOI 10.1103/PhysRevE.100.012139
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  8. Article ; Online: Two ways of escaping from oxidative RNA damage: Selective degradation and cell death.

    Ishii, Takashi / Sekiguchi, Mutsuo

    DNA repair

    2019  Volume 81, Page(s) 102666

    Abstract: Reactive oxygen species (ROS) are produced during normal cellular metabolism, and various oxidized compounds are formed by the ROS attack. Among oxidized bases, 8-oxo-7,8-dihydroguanine (8-oxoG) is most abundant and seems important with respect to the ... ...

    Abstract Reactive oxygen species (ROS) are produced during normal cellular metabolism, and various oxidized compounds are formed by the ROS attack. Among oxidized bases, 8-oxo-7,8-dihydroguanine (8-oxoG) is most abundant and seems important with respect to the maintenance and transfer of genetic information. The accumulation of 8-oxoG in messenger RNA may cause errors during codon-anticodon pairing in the translation process, which may result in the synthesis of abnormal proteins. Organisms that use oxygen as the source of energy production must therefore have some mechanisms to eliminate the deleterious effects of RNA oxidation. Recently, we found two protein factors, AUF1 and PCBP1, which each have a different binding capacity to oxidized RNA. Evidence demonstrated that AUF1 is involved in the specific degradation of oxidized RNA, and that PCBP1 has a function of inducing cell death to eliminate severely damaged RNA.
    MeSH term(s) Apoptosis ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/physiology ; Guanine/analogs & derivatives ; Guanine/metabolism ; Heterogeneous Nuclear Ribonucleoprotein D0/metabolism ; Humans ; Oxidation-Reduction ; Oxidative Stress ; RNA/chemistry ; RNA/metabolism ; RNA, Messenger ; RNA-Binding Proteins/metabolism ; RNA-Binding Proteins/physiology
    Chemical Substances DNA-Binding Proteins ; HNRNPD protein, human ; Heterogeneous Nuclear Ribonucleoprotein D0 ; PCBP1 protein, human ; RNA, Messenger ; RNA-Binding Proteins ; 8-hydroxyguanine (5614-64-2) ; Guanine (5Z93L87A1R) ; RNA (63231-63-0)
    Language English
    Publishing date 2019-07-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2071608-4
    ISSN 1568-7856 ; 1568-7864
    ISSN (online) 1568-7856
    ISSN 1568-7864
    DOI 10.1016/j.dnarep.2019.102666
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: WDR35 is involved in subcellular localization of acetylated tubulin in 293T cells.

    Sekiguchi, Takeshi / Ishii, Takashi / Kobayashi, Hideki / Furuno, Nobuaki

    Biochemical and biophysical research communications

    2021  Volume 547, Page(s) 169–175

    Abstract: WDR35/IFT121 is an intraflagellar transport protein in primary cilia, which is associated with RagA, an mTORC1-activating protein. To elucidate the functions of the interaction between WDR35 and RagA in primary cilia, as well as mTOR signaling, we ... ...

    Abstract WDR35/IFT121 is an intraflagellar transport protein in primary cilia, which is associated with RagA, an mTORC1-activating protein. To elucidate the functions of the interaction between WDR35 and RagA in primary cilia, as well as mTOR signaling, we identified WDR35-interacting proteins using mass spectrometry. We found that WDR35 associates with CCT complex proteins including TCP1/CCT1, which act as molecular chaperones for α-tubulin folding. Immunostaining showed that acetylated α-tubulin was concentrated in the vicinity of primary cilia in 293T cells. In contrast, acetylated tubulin was dispersed in WDR35 partial knockout cells established from 293T cells. Similarly, scattered subcellular localization of acetylated tubulin was observed in RagA knockout cells. RagA was present in the primary cilia of NIH3T3 cells, and the GDP form of RagA exhibited strong binding to WDR35 and negative regulation of primary cilium formation. These results suggest that WDR35 is involved in the subcellular localization of acetylated tubulin in primary cilia via its interactions with TCP1 and/or RagA family proteins.
    MeSH term(s) Acetylation ; Animals ; Cells, Cultured ; Cilia/metabolism ; Cytoskeletal Proteins/metabolism ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Monomeric GTP-Binding Proteins/metabolism ; Signal Transduction ; Subcellular Fractions/metabolism ; Tubulin/chemistry ; Tubulin/metabolism
    Chemical Substances Cytoskeletal Proteins ; Intracellular Signaling Peptides and Proteins ; Tubulin ; WDR35 protein, human ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; RRAGA protein, human (EC 3.6.1.-) ; Monomeric GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2021-02-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2021.01.092
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Involvement of Gtr1p in the oxidative stress response in yeast Saccharomyces cerevisiae

    Sekiguchi, Takeshi / Ishii, Takashi / Kamada, Yoshiaki / Funakoshi, Minoru / Kobayashi, Hideki / Furuno, Nobuaki

    Biochemical and biophysical research communications. 2022 Apr. 02, v. 598

    2022  

    Abstract: Yeast Gtr1p is a GTPase that forms a heterodimer with Gtr2p, another GTPase; it is involved in regulating TORC1 activity in nutrient signaling, including amino acid availability and growth control. Gtr1p is a positive regulator of TORC1, a kinase that ... ...

    Abstract Yeast Gtr1p is a GTPase that forms a heterodimer with Gtr2p, another GTPase; it is involved in regulating TORC1 activity in nutrient signaling, including amino acid availability and growth control. Gtr1p is a positive regulator of TORC1, a kinase that regulates various cellular functions (e.g., protein synthesis and autophagy) under specific nutrient and environmental conditions, including oxidative stress. In this study, we examined the roles of Gtr1p in oxidative stress responses. We found that yeast cells expressing guanosine diphosphatase (GDP)-bound Gtr1p (Gtr1-S20Lp) were resistant to hydrogen peroxide (H₂O₂), whereas guanosine triphosphate (GTP)-bound Gtr1p (Gtr1-Q65Lp) was sensitive to H₂O₂ compared with the wild type. Consistent with these findings, yeast cells lacking Iml1p, a component of the GTPase-activating protein complex for Gtr1p, exhibited the H₂O₂-sensitive phenotype. In gtr1S20L cells, autophagy was highly induced under oxidative stress. gtr1Q65L cells showed decreased expression of the SNQ2 gene, which encodes a multidrug transporter involved in resistance to oxidative stress, and the overexpression of SNQ2 rescued the oxidative stress sensitivity of gtr1Q65L cells. These results suggest that Gtr1p is involved in oxidative stress responses through mechanisms that include autophagy and SNQ2 expression.
    Keywords GTPase-activating proteins ; Saccharomyces cerevisiae ; amino acids ; autophagy ; genes ; guanosine ; guanosine triphosphate ; guanosinetriphosphatase ; hydrogen peroxide ; oxidative stress ; phenotype ; protein synthesis ; research ; stress response ; yeasts
    Language English
    Dates of publication 2022-0402
    Size p. 107-112.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.02.016
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