13 results on '"Purificato, Cristina"'
Search Results
2. 1,25(OH) 2 D3 Differently Modulates the Secretory Activity of IFN-DC and IL4-DC: A Study in Cells from Healthy Donors and MS Patients.
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Sanseverino, Isabella, Rinaldi, Arturo Ottavio, Purificato, Cristina, Cortese, Antonio, Millefiorini, Enrico, and Gauzzi, Maria Cristina
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VITAMIN D receptors ,MACROPHAGE colony-stimulating factor ,VITAMIN D deficiency ,CENTRAL nervous system ,MULTIPLE sclerosis ,DENDRITIC cells ,CEREBROSPINAL fluid ,RHINORRHEA - Abstract
Immune mechanisms play an essential role in driving multiple sclerosis (MS) and altered trafficking and/or activation of dendritic cells (DC) were observed in the central nervous system and cerebrospinal fluid of MS patients. Interferon β (IFNβ) has been used as a first-line therapy in MS for almost three decades and vitamin D deficiency is a recognized environmental risk factor for MS. Both IFNβ and vitamin D modulate DC functions. Here, we studied the response to 1,25-dihydoxyvitamin D3 (1,25(OH)
2 D3) of DC obtained with IFNβ/GM-CSF (IFN-DC) compared to classically derived IL4-DC, in three donor groups: MS patients free of therapy, MS patients undergoing IFNβ therapy, and healthy donors. Except for a decreased CCL2 secretion by IL4-DC from the MS group, no major defects were observed in the 1,25(OH)2 D3 response of either IFN-DC or IL4-DC from MS donors compared to healthy donors. However, the two cell models strongly differed for vitamin D receptor level of expression as well as for basal and 1,25(OH)2 D3-induced cytokine/chemokine secretion. 1,25(OH)2 D3 up-modulated IL6, its soluble receptor sIL6R, and CCL5 in IL4-DC, and down-modulated IL10 in IFN-DC. IFN-DC, but not IL4-DC, constitutively secreted high levels of IL8 and of matrix-metalloproteinase-9, both down-modulated by 1,25(OH)2 D3. DC may contribute to MS pathogenesis, but also provide an avenue for therapeutic intervention. 1,25(OH)2 D3-induced tolerogenic DC are in clinical trial for MS. We show that the protocol of in vitro DC differentiation qualitatively and quantitatively affects secretion of cytokines and chemokines deeply involved in MS pathogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2023
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3. Toll-like receptor cross-talk in human monocytes regulates CC-chemokine production, antigen uptake and immune cell recruitment
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Sabbatucci, Michela, Purificato, Cristina, Fantuzzi, Laura, and Gessani, Sandra
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- 2011
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4. Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB–driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages
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Fantuzzi, Laura, Spadaro, Francesca, Purificato, Cristina, Cecchetti, Serena, Podo, Franca, Belardelli, Filippo, Gessani, Sandra, and Ramoni, Carlo
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- 2008
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5. Transcriptome Profiling of Human Monocyte-Derived Macrophages Upon CCL2 Neutralization Reveals an Association Between Activation of Innate Immune Pathways and Restriction of HIV-1 Gene Expression.
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Covino, Daniela Angela, Kaczor-Urbanowicz, Karolina Elżbieta, Lu, Jing, Chiantore, Maria Vincenza, Fiorucci, Gianna, Vescio, Maria Fenicia, Catapano, Laura, Purificato, Cristina, Galluzzo, Clementina Maria, Amici, Roberta, Andreotti, Mauro, Gauzzi, Maria Cristina, Pellegrini, Matteo, and Fantuzzi, Laura
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GENE expression ,TYPE I interferons ,MACROPHAGES ,APOLIPOPROTEIN B ,DISEASE resistance of plants ,RNA synthesis - Abstract
Macrophages are key targets of human immunodeficiency virus type 1 (HIV-1) infection and main producers of the proinflammatory chemokine CC chemokine ligand 2 (CCL2), whose expression is induced by HIV-1 both in vitro and in vivo. We previously found that CCL2 neutralization in monocyte-derived macrophages (MDMs) strongly inhibited HIV-1 replication affecting post-entry steps of the viral life cycle. Here, we used RNA-sequencing to deeply characterize the cellular factors and pathways modulated by CCL2 blocking in MDMs and involved in HIV-1 replication restriction. We report that exposure to CCL2 neutralizing antibody profoundly affected the MDM transcriptome. Functional annotation clustering of up-regulated genes identified two clusters enriched for antiviral defense and immune response pathways, comprising several interferon-stimulated, and restriction factor coding genes. Transcripts in the clusters were enriched for RELA and NFKB1 targets, suggesting the activation of the canonical nuclear factor κB pathway as part of a regulatory network involving miR-155 up-regulation. Furthermore, while HIV-1 infection caused small changes to the MDM transcriptome, with no evidence of host defense gene expression and type I interferon signature, CCL2 blocking enabled the activation of a strong host innate response in infected macrophage cultures, and potently inhibited viral genes expression. Notably, an inverse correlation was found between levels of viral transcripts and of the restriction factors APOBEC3A (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 A), ISG15, and MX1. These findings highlight an association between activation of innate immune pathways and HIV-1 restriction upon CCL2 blocking and identify this chemokine as an endogenous factor contributing to the defective macrophage response to HIV-1. Therapeutic targeting of CCL2 may thus strengthen host innate immunity and restrict HIV-1 replication. [ABSTRACT FROM AUTHOR]
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- 2020
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6. APOBEC3G/3A Expression in Human Immunodeficiency Virus Type 1-Infected Individuals Following Initiation of Antiretroviral Therapy Containing Cenicriviroc or Efavirenz.
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Covino, Daniela A., Purificato, Cristina, Catapano, Laura, Galluzzo, Clementina M., Gauzzi, Maria Cristina, Vella, Stefano, Lefebvre, Eric, Seyedkazemi, Star, Andreotti, Mauro, and Fantuzzi, Laura
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APOLIPOPROTEIN B ,HIV infections ,HIGHLY active antiretroviral therapy - Abstract
Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro. However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48 weeks post-treatment follow-up. While APOBEC3G expression was unaffected by therapy, APOBEC3A levels increased in CVC but not EFV arm at week 48 of treatment. APOBEC3G expression correlated directly with CD4
+ cell count and CD4+ /CD8+ cell ratio, whereas APOBEC3A levels inversely correlated with plasma soluble CD14. These findings suggest that higher APOBEC3G/3A levels may be associated with protective effects against HIV-1 disease progression and chronic inflammation and warrant further studies. [ABSTRACT FROM AUTHOR]- Published
- 2018
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7. Bovine Lactoferrin-Induced CCL1 Expression Involves Distinct Receptors in Monocyte-Derived Dendritic Cells and Their Monocyte Precursors.
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Latorre, Daniela, Pulvirenti, Nadia, Covino, Daniela Angela, Varano, Barbara, Purificato, Cristina, Rainaldi, Gabriella, Gauzzi, Maria Cristina, Fantuzzi, Laura, Conti, Lucia, Donninelli, Gloria, Del Cornò, Manuela, Sabbatucci, Michela, Gessani, Sandra, and Puddu, Patrizia
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LACTOFERRIN ,IMMUNOREGULATION ,CYTOKINES ,CHEMOKINES ,MONOCYTES ,DENDRITIC cells - Abstract
Lactoferrin (LF) exhibits a wide range of immunomodulatory activities including modulation of cytokine and chemokine secretion. In this study, we demonstrate that bovine LF (bLF) up-modulates, in a concentration- and time-dependent manner, CCL1 secretion in monocytes (Mo) at the early stage of differentiation toward dendritic cells (DCs), and in fully differentiated immature Mo-derived DCs (MoDCs). In both cell types, up-modulation of CCL1 secretion is an early event following bLF-mediated enhanced accumulation of CCL1 transcripts. Notably, bLF-mediated up-regulation of CCL1 involves the engagement of distinct surface receptors in MoDCs and their Mo precursors. We show that bLF-mediated engagement of CD36 contributes to CCL1 induction in differentiating Mo. Conversely, toll-like receptor (TLR)2 blocking markedly reduces bLF-induced CCL1 production in MoDCs. These findings add further evidence for cell-specific differential responses elicited by bLF through the engagement of distinct TLRs and surface receptors. Furthermore, the different responses observed at early and late stages of Mo differentiation towards DCs may be relevant in mediating bLF effects in specific body districts, where these cell types may be differently represented in physiopathological conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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8. Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation.
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Sabbatucci, Michela, Covino, Daniela Angela, Purificato, Cristina, Mallano, Alessandra, Federico, Maurizio, Jing Lu, Rinaldi, Arturo Ottavio, Pellegrini, Matteo, Bona, Roberta, Michelini, Zuleika, Cara, Andrea, Vella, Stefano, Gessani, Sandra, Andreotti, Mauro, and Fantuzzi, Laura
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NEUTRALIZATION (Chemistry) ,CHEMOKINES ,LIGANDS (Biochemistry) ,MACROPHAGES ,SINGLE crystals - Abstract
Background: Macrophages are key targets of HIV-1 infection. We have previously described that the expression of CC chemokine ligand 2 (CCL2) increases during monocyte differentiation to macrophages and it is further up-modulated by HIV-1 exposure. Moreover, CCL2 acts as an autocrine factor that promotes viral replication in infected macrophages. In this study, we dissected the molecular mechanisms by which CCL2 neutralization inhibits HIV-1 replication in monocyte-derived macrophages (MDM), and the potential involvement of the innate restriction factors protein sterile alpha motif (SAM) histidine/aspartic acid (HD) domain containing 1 (SAMHD1) and apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) family members. Results: CCL2 neutralization potently reduced the number of p24 Gag+ cells during the course of either productive or single cycle infection with HIV-1. In contrast, CCL2 blocking did not modify entry of HIV-1 based Virus Like Particles, thus demonstrating that the restriction involves post-entry steps of the viral life cycle. Notably, the accumulation of viral DNA, both total, integrated and 2-LTR circles, was strongly impaired by neutralization of CCL2. Looking for correlates of HIV-1 DNA accumulation inhibition, we found that the antiviral effect of CCL2 neutralization was independent of the modulation of SAMHD1 expression or function. Conversely, a strong and selective induction of APOBEC3A expression, to levels comparable to those of freshly isolated monocytes, was associated with the inhibition of HIV-1 replication mediated by CCL2 blocking. Interestingly, the CCL2 neutralization mediated increase of APOBEC3A expression was type I IFN independent. Moreover, the transcriptome analysis of the effect of CCL2 blocking on global gene expression revealed that the neutralization of this chemokine resulted in the upmodulation of additional genes involved in the defence response to viruses. Conclusions: Neutralization of endogenous CCL2 determines a profound restriction of HIV-1 replication in primary MDM affecting post-entry steps of the viral life cycle with a mechanism independent of SAMHD1. In addition, CCL2 blocking is associated with induction of APOBEC3A expression, thus unravelling a novel mechanism which might contribute to regulate the expression of innate intracellular viral antagonists in vivo. Thus, our study may potentially lead to the development of new therapeutic strategies for enhancing innate cellular defences against HIV-1 and protecting macrophages from infection. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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9. Increased Circulating Levels of Vitamin D Binding Protein in MS Patients.
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Rinaldi, Arturo Ottavio, Sanseverino, Isabella, Purificato, Cristina, Cortese, Antonio, Mechelli, Rosella, Francisci, Silvia, Salvetti, Marco, Millefiorini, Enrico, Gessani, Sandra, and Gauzzi, Maria Cristina
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VITAMIN D ,CARRIER proteins ,MULTIPLE sclerosis ,ETIOLOGY of diseases ,ALBUMINS ,THERAPEUTIC use of interferons - Abstract
Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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10. Nuclear Phosphoinositide-Specific Phospholipase C β1 Controls Cytoplasmic CCL2 mRNA Levels in HIV-1 gp120-Stimulated Primary Human Macrophages.
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Spadaro, Francesca, Cecchetti, Serena, Purificato, Cristina, Sabbatucci, Michela, Podo, Franca, Ramoni, Carlo, Gessani, Sandra, and Fantuzzi, Laura
- Subjects
PHOSPHOINOSITIDES ,CYTOPLASM ,MESSENGER RNA ,MACROPHAGES ,HIV-1 glycoprotein 120 ,CHEMOKINES ,WESTERN immunoblotting ,HOST-parasite relationships - Abstract
HIV-1 envelope glycoprotein gp120 induces, independently of infection, the release of CCL2 from macrophages. In turn, this chemokine acts as an autocrine factor enhancing viral replication. In this study, we show for the first time that phosphoinositide-specific phospholipase C (PI-PLC) is required for the production of CCL2 triggered by gp120 in macrophages. Using a combination of confocal laser-scanner microscopy, pharmacologic inhibition, western blotting and fluorescence-activated cell sorter analysis, we demonstrate that gp120 interaction with CCR5 leads to nuclear localization of the PI-PLC β1 isozyme mediated by mitogen-activated protein kinase ERK-1/2. Notably, phosphatidylcholine-specific phospholipase C (PC-PLC), previously reported to be required for NF-kB-mediated CCL2 production induced by gp120 in macrophages, drives both ERK1/2 activation and PI-PLC β1 nuclear localization induced by gp120. PI-PLC β1 activation through CCR5 is also triggered by the natural chemokine ligand CCL4, but independently of ERK1/2. Finally, PI-PLC inhibition neither blocks gp120-mediated NF-kB activation nor overall accumulation of CCL2 mRNA, whereas it decreases CCL2 transcript level in the cytoplasm. These results identify nuclear PI-PLC β1 as a new intermediate in the gp120-triggered PC-PLC-driven signal transduction pathway leading to CCL2 secretion in macrophages. The finding that a concerted gp120-mediated signaling involving both PC- and PI-specific PLCs is required for the expression of CCL2 in macrophages suggests that this signal transduction pathway may also be relevant for the modulation of viral replication in these cells. Thus, this study may contribute to identify novel targets for therapeutic intervention in HIV-1 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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11. Human Immunodeficiency Virus Type 1 gp120 Induces Abnormal Maturation and Functional Alterations of Dendritic Cells: a Novel Mechanism for AIDS Pathogenesis.
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Fantuzzi, Laura, Purificato, Cristina, Donato, Karim, Belardelli, Filippo, and Gessani, Sandra
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DENDRITIC cells , *PATHOGENIC microorganisms , *HIV infections , *HIV , *PHENOTYPES , *CYTOKINES , *AIDS - Abstract
Dendritic cells (DCs) play a crucial role in bridging innate and acquired immune responses to pathogens. In human immunodeficiency virus type 1 (HIV-1) infection, immature DCs (iDCs) are also main targets for HIV-1 at the mucosal level. In this study, we evaluated the effects of HIV-1-DC interactions on the maturation and functional activity of these cells. Exposure of human monocyte-derived iDCs to either aldrithiol-2-inactivated HIV-1 or gp120 led to an upmodulation of activation markers indicative of functional maturation. Despite their phenotype, these cells retained antigen uptake capacity and showed an impaired ability to secrete cytokines or chemokines and to induce T-cell proliferation. Although gp120 did not interfere with DC differentiation, the capacity of these cells to produce interleukin-12 (IL-12) upon maturation was markedly reduced. Likewise, iDCs stimulated by classical maturation factors in the presence of gp120 lacked allostimulatory capacity and did not produce IL-12, in spite of their phenotype typical of activated DCs. Exogenous addition of IL-12 restores the allostimulatory capacity of gp120-exposed DCs. The finding that gp120 induces abnormal maturation of DCs linked to profound suppression of their activities unravels a novel mechanism by which HIV can lead to immune dysfunction in AIDS patients. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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12. Dual requirement for STAT signaling in dendritic cell immunobiology.
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Donninelli, Gloria, Sanseverino, Isabella, Purificato, Cristina, Gessani, Sandra, and Gauzzi, Maria Cristina
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SOLAR cells , *PHOTOVOLTAIC cells , *IRRADIATION , *RADIATION , *SEMICONDUCTORS - Abstract
Dendritic cells (DC) represent an attractive target for therapeutic manipulation of the immune system and enhancement of insufficient immune response in cancer. STAT family members play key roles in the differentiation and activation of DC, a feature that is currently being exploited in DC-based therapies. We previously reported that the small-molecule Stattic, originally developed as a STAT3-specific inhibitor, also inhibits STAT1 and STAT2 phosphorylation in DC exposed to cytokines or LPS. Aim of this study was to investigate the functional consequences of in vitro treatment with Stattic on DC immunobiology. Interestingly, we observed an opposite effect of Stattic on DC immunophenotype depending on the activation state. While the expression of costimulatory, coinhibitory, MHC class II and CD83 molecules was enhanced in immature DC exposed to Stattic, the LPS induced up-modulation of these molecules was strongly repressed. An effective blockade of LPS-induced secretion of proinflammatory cytokines and capacity to stimulate a Th1 polarization was also observed in the presence of Stattic. Our results indicate that the immunological consequences of STAT inhibition in DC vary depending on the cell activation state. This knowledge is of relevance for anticipating potential effects of STAT-targeted therapeutics, and pursuing selective DC manipulation in clinical applications. [ABSTRACT FROM AUTHOR]
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- 2018
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13. CCL2 induction by 1,25(OH)2D3 in dendritic cells from healthy donors and multiple sclerosis patients.
- Author
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Sanseverino, Isabella, Rinaldi, Arturo O., Purificato, Cristina, Cortese, Antonio, Millefiorini, Enrico, Gessani, Sandra, and Gauzzi, M. Cristina
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MULTIPLE sclerosis , *CALCITRIOL , *DENDRITIC cells , *ORGAN donors , *INFLAMMATION , *CYTOKINES , *VITAMIN D deficiency , *PATIENTS - Abstract
CCL2 plays a pivotal role in the recruitment of different immune cells to sites of inflammation and evidence indicates its involvement in multiple sclerosis (MS) pathogenesis. MS lesions are characterized by an inflammatory infiltrate, whose nature is controlled by chemokines and cytokines, and elevated expression of CCL2 has been found in acute and chronic MS plaques within the brain. Vitamin D deficiency is currently considered one of the main environmental MS risk factors. In this study we analyzed the role of 1,25(OH) 2 D 3 , the bioactive vitamin D metabolite, in the regulation of CCL2 expression by dendritic cells (DC) obtained from healthy donors and relapsing-remitting MS patients. We report that 1,25(OH) 2 D 3 , as well as 25OHD 3 , its main blood precursor, induce the secretion of high levels of CCL2. 1,25(OH) 2 D 3 -induced CCL2 levels are comparable to those secreted in response to a classical DC maturation stimulus. Moreover, we observed that 1,25(OH) 2 D 3 is able to induce a significant CCL2 secretion in DC obtained from relapsing-remitting MS patients, although CCL2 levels in these latter are lower with respect to healthy controls. The cause(s) of this apparently defective response of DC from patients and its consequences in the context of MS remain to be elucidated. However, we propose CCL2 as a molecular player contributing to the immunomodulatory activity of 1,25(OH) 2 D 3 on DC, and hypothesize a role for this chemokine in the response of MS patients to vitamin D therapy. This article is part of a Special Issue entitled ‘16th Vitamin D Workshop’. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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