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Veillette A: The SAP family: a new class of adaptor-like molecules that regulates immune cell functions. Sci STKE 2002:E8.
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This paper describes the cloning and characterisation of NTB-A, a novel SLAM-related receptor that interacts with SAP. NTB-A is expressed in NK cells, T cells and B cells. In NK cells, engagement of NTB-A by antibodies was shown to trigger cell cytotoxicity. This function was dependent on SAP. Intriguingly, in the absence of SAP, NTB-A engagement provoked an inhibition of NK cell-mediated cytotoxicity. Alterations in the function of NTB-A may account for part of the inability of XLP patients to mount appropriate cytotoxic responses against EBV-infected cells.
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Bottino C., Falco M., Parolini S., Marcenaro E., Augugliaro R., Sivori S., Landi E., Biassoni R., Notarangelo L.D., Moretta L., Moretta A. NTB-A, a novel SH2D1A-associated surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus-infected B cells in X-linked lymphoproliferative disease. J. Exp. Med. 194:2001;235-246 This paper describes the cloning and characterisation of NTB-A, a novel SLAM-related receptor that interacts with SAP. NTB-A is expressed in NK cells, T cells and B cells. In NK cells, engagement of NTB-A by antibodies was shown to trigger cell cytotoxicity. This function was dependent on SAP. Intriguingly, in the absence of SAP, NTB-A engagement provoked an inhibition of NK cell-mediated cytotoxicity. Alterations in the function of NTB-A may account for part of the inability of XLP patients to mount appropriate cytotoxic responses against EBV-infected cells.
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Bottino, C.1
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Cutting edge: Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family
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This manuscript reports on the cloning and characterisation of CRACC, a novel receptor belonging to the SLAM family, which is expressed in NK cells, DCs, T cells and B cells. Interestingly, CRACC was shown to lack detectable association with SAP. In NK cells, CRACC stimulation by antibodies resulted in NK cell-mediated cytotoxicity. In NK cells from XLP patients, this stimulatory function was preserved, supporting the idea that CRACC does not associate with SAP.
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Bouchon A., Cella M., Grierson H.L., Cohen J.I., Colonna M. Cutting edge: activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family. J. Immunol. 167:2001;5517-5521 This manuscript reports on the cloning and characterisation of CRACC, a novel receptor belonging to the SLAM family, which is expressed in NK cells, DCs, T cells and B cells. Interestingly, CRACC was shown to lack detectable association with SAP. In NK cells, CRACC stimulation by antibodies resulted in NK cell-mediated cytotoxicity. In NK cells from XLP patients, this stimulatory function was preserved, supporting the idea that CRACC does not associate with SAP.
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Bouchon, A.1
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Signalling lymphocytic activation molecule (CDw150) is homophilic but self-associates with very low affinity
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Mavaddat N., Mason D.W., Atkinson P.D., Evans E.J., Gilbert R.J., Stuart D.I., Fennelly J.A., Barclay A.N., Davis S.J., Brown M.H. Signalling lymphocytic activation molecule (CDw150) is homophilic but self-associates with very low affinity. J. Biol. Chem. 275:2000;28100-28109.
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0035478348
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CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: Adhesion is mediated by Ig-like domain 1
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Martin M., Romero X., de la Fuente M.A., Tovar V., Zapater N., Esplugues E., Pizcueta P., Bosch J., Engel P. CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1. J. Immunol. 167:2001;3668-3676.
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Martin, M.1
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0037105245
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CS1, a novel member of the CD2 family, is homophilic and regulates NK cell function
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Kumaresan P., Lai W., Chuang S., Bennett M., Mathew P. CS1, a novel member of the CD2 family, is homophilic and regulates NK cell function. Mol. Immunol. 39:2002;1-8.
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12
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0034889004
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Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product
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The authors of this report analysed the physical and functional interactions between SLAM and SAP using a model T-cell line. SLAM-SAP interaction was shown to result in an intracellular tyrosine phosphorylation signal that involved SLAM itself, the 5′ inositol phosphatase SHIP-1, the adaptors Dok-1, Dok-2 and Shc, as well as the Ras GTPase-activating protein Ras-GAP. This signal was coupled to a selective inhibition of IFN-γ production by activated T cells. Additional studies showed that SAP was required for SLAM signalling as a result of its capacity to promote the selective recruitment and activation of FynT, a Src-related PTK.
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Latour S., Gish G., Helgason C.D., Humphries R.K., Pawson T., Veillette A. Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product. Nat. Immunol. 2:2001;681-690 The authors of this report analysed the physical and functional interactions between SLAM and SAP using a model T-cell line. SLAM-SAP interaction was shown to result in an intracellular tyrosine phosphorylation signal that involved SLAM itself, the 5′ inositol phosphatase SHIP-1, the adaptors Dok-1, Dok-2 and Shc, as well as the Ras GTPase-activating protein Ras-GAP. This signal was coupled to a selective inhibition of IFN-γ production by activated T cells. Additional studies showed that SAP was required for SLAM signalling as a result of its capacity to promote the selective recruitment and activation of FynT, a Src-related PTK.
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Latour, S.1
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13
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0034710650
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SLAM (CDw150) is a cellular receptor for measles virus
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Tatsuo H., Ono N., Tanaka K., Yanagi Y. SLAM (CDw150) is a cellular receptor for measles virus. Nature. 406:2000;893-897.
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Tatsuo, H.1
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14
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0035915993
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CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus
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Together with [13], this manuscript demonstrates that SLAM is the lymphoid-specific receptor for measles virus in humans.
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Hsu E.C., Iorio C., Sarangi F., Khine A.A., Richardson C.D. CDw150(SLAM) is a receptor for a lymphotropic strain of measles virus and may account for the immunosuppressive properties of this virus. Virology. 279:2001;9-21 Together with [13], this manuscript demonstrates that SLAM is the lymphoid-specific receptor for measles virus in humans.
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Virology
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Hsu, E.C.1
Iorio, C.2
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Morra M., Lu J., Poy F., Martin M., Sayos J., Calpe S., Gullo C., Howie D., Rietdijk S., Thompson A.et al. Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells. EMBO J. 20:2001;5840-5852.
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The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM
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Sayos J., Wu C., Morra M., Wang N., Zhang X., Allen D., van Schaik S., Notarangelo L., Geha R., Roncarolo M.G.et al. The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM. Nature. 395:1998;462-469.
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Sayos, J.1
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Nichols K.E., Harkin D.P., Levitz S., Krainer M., Kolquist K.A., Genovese C., Bernard A., Ferguson M., Zuo L., Snyder E.et al. Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome. Proc. Natl. Acad Sci. USA. 95:1998;13765-13770.
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Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene
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Coffey A.J., Brooksbank R.A., Brandau O., Oohashi T., Howell G.R., Bye J.M., Cahn A.P., Durham J., Heath P., Wray P.et al. Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. Nat. Genet. 20:1998;129-135.
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Seemayer T.A., Gross T.G., Egeler R.M., Pirruccello S.J., Davis J.R., Kelly C.M., Okano M., Lanyi A., Sumegi J. X-linked lymphoproliferative disease: twenty-five years after the discovery. Pediatr. Res. 38:1995;471-478.
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SAP controls T cell responses to virus and terminal differentiation of TH2 cells
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Wu, C.1
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22
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0035912823
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Altered lymphocyte responses and cytokine production in mice deficient in the X-linked lymphoproliferative disease gene SH2D1A/DSHP/SAP
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••] show that mice with a disrupted sap gene have aberrant immune responses when challenged with LCMV, Toxoplasma gondii or Leishmania major. These altered responses were characterised by increased IFN-γ production and decreased IL-4 production. In vitro studies also indicated that T lymphocytes from SAP-deficient mice failed to differentiate into Th2 cells.
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••] show that mice with a disrupted sap gene have aberrant immune responses when challenged with LCMV, Toxoplasma gondii or Leishmania major. These altered responses were characterised by increased IFN-γ production and decreased IL-4 production. In vitro studies also indicated that T lymphocytes from SAP-deficient mice failed to differentiate into Th2 cells.
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Czar, M.J.1
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Chen, A.7
Sher, A.8
Duckett, C.S.9
Ahmed, R.10
Schwartzberg, P.L.11
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23
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0037448564
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SAP is required for the generation of long term humoral immunity
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This paper demonstrates that the virus-induced generation of memory B cells and germinal centres is defective in SAP-deficient mice. This is seemingly caused by an intrinsic T-cell help defect.
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Crotty S., Kersh E.N., Cannons J., Schwartzberg P.L., Ahmed R. SAP is required for the generation of long term humoral immunity. Nature. 421:2003;282-287 This paper demonstrates that the virus-induced generation of memory B cells and germinal centres is defective in SAP-deficient mice. This is seemingly caused by an intrinsic T-cell help defect.
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Nature
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Crotty, S.1
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24
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2B4: An NK cell activating receptor with unique specificity and signal transduction mechanism
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Nakajima H., Colonna M. 2B4: an NK cell activating receptor with unique specificity and signal transduction mechanism. Hum. Immunol. 61:2000;39-43.
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Nakajima, H.1
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X-linked lymphoproliferative disease. 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells
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Parolini S., Bottino C., Falco M., Augugliaro R., Giliani S., Franceschini R., Ochs H.D., Wolf H., Bonnefoy J.Y., Biassoni R.et al. X-linked lymphoproliferative disease. 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells. J. Exp. Med. 192:2000;337-346.
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Parolini, S.1
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26
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0034664724
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Functional requirement for SAP in 2B4-mediated activation of human natural killer cells as revealed by the X-linked lymphoproliferative syndrome
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Tangye S.G., Phillips J.H., Lanier L.L., Nichols K.E. Functional requirement for SAP in 2B4-mediated activation of human natural killer cells as revealed by the X-linked lymphoproliferative syndrome. J. Immunol. 165:2000;2932-2936.
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Patients with X-linked lymphoproliferative disease have a defect in 2B4 receptor-mediated NK cell cytotoxicity
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Nakajima H., Cella M., Bouchon A., Grierson H.L., Lewis J., Duckett C.S., Cohen J.I., Colonna M. Patients with X-linked lymphoproliferative disease have a defect in 2B4 receptor-mediated NK cell cytotoxicity. Eur. J. Immunol. 30:2000;3309-3318.
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Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition
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Poy F., Yaffe M.B., Sayos J., Saxena K., Morra M., Sumegi J., Cantley L.C., Terhorst C., Eck M.J. Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition. Mol. Cell. 4:1999;555-561.
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0033518296
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Novel mode of ligand binding by the SH2 domain of the human XLP disease gene product SAP/SH2D1A
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Li S.C., Gish G., Yang D., Coffey A.J., Forman-Kay J.D., Ernberg I., Kay L.E., Pawson T. Novel mode of ligand binding by the SH2 domain of the human XLP disease gene product SAP/SH2D1A. Curr. Biol. 9:1999;1355-1362.
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Li, S.C.1
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A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: Structural basis and relevance to the XLP syndrome
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Together with [28,29], this paper describes the analysis of the mode of interaction of the SAP or EAT-2 SH2 domains with SRRs by crystallography, nuclear magnetic resonance and random peptide library screening studies. These interactions were shown to be mediated by the tyrosine-based motif TIYxxV/I, located in the cytoplasmic domain of SRRs. Remarkably, the binding of the SAP/EAT-2 SH2 domain to this motif involved a third point of contact between the SH2 domain and residues located amino-terminal to the phosphotyrosine, resulting in a 'three-pronged' interaction. In the case of SLAM, the interaction with the SAP SH2 domain did not require phosphorylation of the tyrosine, but was strengthened by phosphorylation.
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Hwang P.M., Li C., Morra M., Lillywhite J., Muhandiram D.R., Gertler F., Terhorst C., Kay L.E., Pawson T., Forman-Kay J.D., Li S.C. A "three-pronged" binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome. EMBO J. 21:2002;314-323 Together with [28,29], this paper describes the analysis of the mode of interaction of the SAP or EAT-2 SH2 domains with SRRs by crystallography, nuclear magnetic resonance and random peptide library screening studies. These interactions were shown to be mediated by the tyrosine-based motif TIYxxV/I, located in the cytoplasmic domain of SRRs. Remarkably, the binding of the SAP/EAT-2 SH2 domain to this motif involved a third point of contact between the SH2 domain and residues located amino-terminal to the phosphotyrosine, resulting in a 'three-pronged' interaction. In the case of SLAM, the interaction with the SAP SH2 domain did not require phosphorylation of the tyrosine, but was strengthened by phosphorylation.
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EMBO J.
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Hwang, P.M.1
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Terhorst, C.7
Kay, L.E.8
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Forman-Kay, J.D.10
Li, S.C.11
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31
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0037322612
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Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation
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This manuscript describes the mechanism by which SAP promotes the recruitment and activation of FynT in the SLAM-SAP signalling pathway. It was shown that SAP interacts directly with the SH3 domain of FynT. This interaction involves a nonproline-based motif located in the SH2 domain of SAP that is independent of the phosphotyrosine-binding pocket. Mutation of arginine residue 78 of SAP abolished the capacity of SAP to bind to FynT, as well as SLAM-induced intracellular protein tyrosine phosphorylation and modulation of cytokine production in T cells.
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Latour S., Roncagalli R., Chen R., Bakinowski M., Shi X., Schwartzberg P.L., Davidson D., Veillette A. Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of receptor signalling in immune regulation. Nat. Cell Biol. 5:2003;149-154 This manuscript describes the mechanism by which SAP promotes the recruitment and activation of FynT in the SLAM-SAP signalling pathway. It was shown that SAP interacts directly with the SH3 domain of FynT. This interaction involves a nonproline-based motif located in the SH2 domain of SAP that is independent of the phosphotyrosine-binding pocket. Mutation of arginine residue 78 of SAP abolished the capacity of SAP to bind to FynT, as well as SLAM-induced intracellular protein tyrosine phosphorylation and modulation of cytokine production in T cells.
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Nat. Cell Biol.
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Latour, S.1
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Davidson, D.7
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32
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