Pub Date : 2009-01-01DOI: 10.1016/B978-0-12-369441-6.00005-2
B. Gomperts, I. Kramer, P. Tatham
{"title":"Effector enzymes coupled to GTP-binding proteins: Adenylyl cyclase and phospholipase C","authors":"B. Gomperts, I. Kramer, P. Tatham","doi":"10.1016/B978-0-12-369441-6.00005-2","DOIUrl":"https://doi.org/10.1016/B978-0-12-369441-6.00005-2","url":null,"abstract":"","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"1 1","pages":"131-157"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/B978-0-12-369441-6.00005-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54043783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. E. Avendaño-Vázquez, Alejandro Cabrera-Wrooman, Christian C Colín-Santana, J. García-Sáinz
Lysophosphatidic acid is a local hormone / autacoid / growth factor, which induces a plethora of actions in the majority of cells in our organism. These actions include, among many others, the following: cell migration, proliferation and surviving, induction of gene transcription, platelet aggregation, smooth muscle contraction, myelinization, neurotransmitter release, cytoskeletal reorganization during the stress fiber formation, establishment of focal adhesions, neurite retraction, and cell rounding. The actions of lysophosphatidic acid are mediated through a family of G protein coupled receptors that includes five receptor subtypes, i.e. LPA1,–5 receptors. These receptors couple to different G proteins, mainly Gi, Gq and G12/13 and their signaling pathways, besides there is evidence that they can transactivate EGF receptors to mediate some of their actions. The LPA1 receptor was the first subtype to be cloned for this lysophospholipid. It plays an important role in development, is expressed in many cells and tissues and has been the most extensively studied. The present review presents current knowledge on the structure, function and regulation of this receptor subtype, its possible involvement in pathological conditions and suggests certain areas in which current knowledge is insufficient and further research is required.
{"title":"Lysophosphatidic acid LPA1 receptor close‐up","authors":"S. E. Avendaño-Vázquez, Alejandro Cabrera-Wrooman, Christian C Colín-Santana, J. García-Sáinz","doi":"10.1002/SITA.200700138","DOIUrl":"https://doi.org/10.1002/SITA.200700138","url":null,"abstract":"Lysophosphatidic acid is a local hormone / autacoid / growth factor, which induces a plethora of actions in the majority of cells in our organism. These actions include, among many others, the following: cell migration, proliferation and surviving, induction of gene transcription, platelet aggregation, smooth muscle contraction, myelinization, neurotransmitter release, cytoskeletal reorganization during the stress fiber formation, establishment of focal adhesions, neurite retraction, and cell rounding. The actions of lysophosphatidic acid are mediated through a family of G protein coupled receptors that includes five receptor subtypes, i.e. LPA1,–5 receptors. These receptors couple to different G proteins, mainly Gi, Gq and G12/13 and their signaling pathways, besides there is evidence that they can transactivate EGF receptors to mediate some of their actions. The LPA1 receptor was the first subtype to be cloned for this lysophospholipid. It plays an important role in development, is expressed in many cells and tissues and has been the most extensively studied. The present review presents current knowledge on the structure, function and regulation of this receptor subtype, its possible involvement in pathological conditions and suggests certain areas in which current knowledge is insufficient and further research is required.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"61 3","pages":"351-363"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200700138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial: Signal transduction in Mexico","authors":"J. García-Sáinz, Y. Rosenstein","doi":"10.1002/SITA.200890001","DOIUrl":"https://doi.org/10.1002/SITA.200890001","url":null,"abstract":"","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"291 2","pages":"349-350"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200890001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Membrane receptors for the Fc portion of IgG antibodies (FcγR) are expressed by most cells of the immune system. Recent research has revealed that, besides their role in effector functions mediated by leukocytes, FcγR also participate in the antibody-mediated regulation of many phenomena in the afferent phase of immune responses and in the homeostasis of the immune system. Here, we review recent findings on the mechanisms of signal transduction by these receptors as well as on the modulation of FcγR signaling by signal regulators and/or by the activation state of the cell.
{"title":"Early biochemical events in leukocyte activation through receptors for IgG","authors":"E. Ortega, I. Soto-Cruz","doi":"10.1002/SITA.200700143","DOIUrl":"https://doi.org/10.1002/SITA.200700143","url":null,"abstract":"Membrane receptors for the Fc portion of IgG antibodies (FcγR) are expressed by most cells of the immune system. Recent research has revealed that, besides their role in effector functions mediated by leukocytes, FcγR also participate in the antibody-mediated regulation of many phenomena in the afferent phase of immune responses and in the homeostasis of the immune system. Here, we review recent findings on the mechanisms of signal transduction by these receptors as well as on the modulation of FcγR signaling by signal regulators and/or by the activation state of the cell.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"42 3","pages":"415-426"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200700143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Specific receptors for antibodies, named Fc receptors, and for extracellular matrix proteins, named integrins, contribute to phagocyte activation. Because phagocyte activation is the mechanism whereby most of the potential pathogens are ultimately destroyed, there is a lot of interest to elucidate the biochemical signals that Fc receptors and integrins induce to activate phagocyte functions. This review describes the main signal transduction pathways that are initiated by Fc receptors and integrins in phagocytic leukocytes, with emphasis on the activation of phagocytosis and gene expression. New findings on the common signaling pathways used by Fc receptors and integrins are also discussed.
{"title":"Fc receptor and integrin signaling in phagocytes","authors":"C. Rosales","doi":"10.1002/SITA.200700141","DOIUrl":"https://doi.org/10.1002/SITA.200700141","url":null,"abstract":"Specific receptors for antibodies, named Fc receptors, and for extracellular matrix proteins, named integrins, contribute to phagocyte activation. Because phagocyte activation is the mechanism whereby most of the potential pathogens are ultimately destroyed, there is a lot of interest to elucidate the biochemical signals that Fc receptors and integrins induce to activate phagocyte functions. This review describes the main signal transduction pathways that are initiated by Fc receptors and integrins in phagocytic leukocytes, with emphasis on the activation of phagocytosis and gene expression. New findings on the common signaling pathways used by Fc receptors and integrins are also discussed.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"35 16","pages":"386-401"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200700141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. González-Espinosa, J. Medina-Tamayo, E. Sánchez-Miranda, Juan Pablo Benitez-Garrido, Alejandro Martin Avila-Hernandez, A. Padilla, Jonathan Garcia-Roman
Signaling through the high affinity receptor for IgE (FceRI) on mast cells comprises an intricate network of protein-protein modifications and interactions leading to mast cell degranulation, lipid-derived mediator production and cytokine release. Depending on the tissue where mast cells are activated, mediator release can induce distinct allergy symptoms. FceRI receptor mainly couples to at least two Src family kinases (Lyn and Fyn), which are responsible for the initiation of the signaling cascade. Distinct membrane bound adapters couple the initial signal to the formation of particular multi-molecular complexes that, in turn, will mediate a specific final response. In this review we summarize the molecular mechanisms initiated by the FceRI receptor on mast cells that have been involved in cytokine expression. At the same time, some conditions where the main signal transduction mechanism is modified will be analyzed in order to understand how locally produced mediators could alter IgE-antigen-induced allergic responses.
{"title":"Signaling through the high affinity IgE receptor and conditions able to modify IgE‐antigen responsiveness of mast cells","authors":"C. González-Espinosa, J. Medina-Tamayo, E. Sánchez-Miranda, Juan Pablo Benitez-Garrido, Alejandro Martin Avila-Hernandez, A. Padilla, Jonathan Garcia-Roman","doi":"10.1002/SITA.200700142","DOIUrl":"https://doi.org/10.1002/SITA.200700142","url":null,"abstract":"Signaling through the high affinity receptor for IgE (FceRI) on mast cells comprises an intricate network of protein-protein modifications and interactions leading to mast cell degranulation, lipid-derived mediator production and cytokine release. Depending on the tissue where mast cells are activated, mediator release can induce distinct allergy symptoms. FceRI receptor mainly couples to at least two Src family kinases (Lyn and Fyn), which are responsible for the initiation of the signaling cascade. Distinct membrane bound adapters couple the initial signal to the formation of particular multi-molecular complexes that, in turn, will mediate a specific final response. In this review we summarize the molecular mechanisms initiated by the FceRI receptor on mast cells that have been involved in cytokine expression. At the same time, some conditions where the main signal transduction mechanism is modified will be analyzed in order to understand how locally produced mediators could alter IgE-antigen-induced allergic responses.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"16 5","pages":"402-414"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200700142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune cells functions are regulated through the orchestrated intervention of immune receptors that recognize non-self peptides or pathogen associated molecular patterns and of molecules that modulate the signals these receptors generate. These molecules, known as accessory or co-receptor molecules, sense the environment, setting the threshold for cell activation, as well as instructing the cells to ensure self-tolerance and homeostasis. CD43 is an abundant cell surface protein, expressed on nearly all lineages of hematopoietic cells. Multiple, and sometimes opposite functions, have been attributed to CD43: adhesion and anti-adhesion, locomotion, cellular activation, differentiation, proliferation and apoptosis. Here we will summarize recent developments in our understanding of the role this molecule plays in different cell types. In particular, we will illustrate the role of CD43 as a T cell accessory molecule, capable of generating intracellular signals, independently of or in coordination with the TCR, actively modulating T cell response. In addition, we review new functions for this molecule, in non-immune cells.
{"title":"CD43 – One molecule, many tales to recount","authors":"G. Pedraza-Alva, Y. Rosenstein","doi":"10.1002/SITA.200700140","DOIUrl":"https://doi.org/10.1002/SITA.200700140","url":null,"abstract":"Immune cells functions are regulated through the orchestrated intervention of immune receptors that recognize non-self peptides or pathogen associated molecular patterns and of molecules that modulate the signals these receptors generate. These molecules, known as accessory or co-receptor molecules, sense the environment, setting the threshold for cell activation, as well as instructing the cells to ensure self-tolerance and homeostasis. CD43 is an abundant cell surface protein, expressed on nearly all lineages of hematopoietic cells. Multiple, and sometimes opposite functions, have been attributed to CD43: adhesion and anti-adhesion, locomotion, cellular activation, differentiation, proliferation and apoptosis. Here we will summarize recent developments in our understanding of the role this molecule plays in different cell types. In particular, we will illustrate the role of CD43 as a T cell accessory molecule, capable of generating intracellular signals, independently of or in coordination with the TCR, actively modulating T cell response. In addition, we review new functions for this molecule, in non-immune cells.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"17 14","pages":"372-385"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200700140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemokines are low molecular weight soluble mediators that control leukocyte trafficking during lymphocyte homeostasis and inflammation. Chemokine-mediated signaling is triggered upon chemokine binding to seven transmembrane G protein-coupled receptors. Multiple signaling pathways are activated leading to cytoskeleton rearrangements, gene transcription and receptor internalization or degradation Among the signaling molecules involved in chemokine mediated signaling, the Jak-Stat pathway has been shown to be activated very early after chemokine stimulation. There is growing evidence showing the involvement of particular Jaks and Stats, in chemokine receptor signaling both in cell lines and primary cells. Jak/Stat phosphorylation is detected soon after chemokine receptor dimerization or in response to chemokines. Also, pharmacological inhibition of Jaks, or the use of Jak deficient lymphocytes results in inhibition of chemokine-mediated responses, such as chemotaxis or integrin-mediated adhesion. This review summarizes the current data describing the involvement of the Jak-Stat pathway in chemokine-mediated signaling in T lymphocytes and discusses the potential crosstalk with other TCR and cytokine-mediated signaling pathways.
{"title":"The role of the Jak‐Stat pathway in chemokine‐mediated signaling in T lymphocytes","authors":"G. Soldevila, E. García-Zepeda","doi":"10.1002/SITA.200700144","DOIUrl":"https://doi.org/10.1002/SITA.200700144","url":null,"abstract":"Chemokines are low molecular weight soluble mediators that control leukocyte trafficking during lymphocyte homeostasis and inflammation. Chemokine-mediated signaling is triggered upon chemokine binding to seven transmembrane G protein-coupled receptors. Multiple signaling pathways are activated leading to cytoskeleton rearrangements, gene transcription and receptor internalization or degradation Among the signaling molecules involved in chemokine mediated signaling, the Jak-Stat pathway has been shown to be activated very early after chemokine stimulation. There is growing evidence showing the involvement of particular Jaks and Stats, in chemokine receptor signaling both in cell lines and primary cells. Jak/Stat phosphorylation is detected soon after chemokine receptor dimerization or in response to chemokines. Also, pharmacological inhibition of Jaks, or the use of Jak deficient lymphocytes results in inhibition of chemokine-mediated responses, such as chemotaxis or integrin-mediated adhesion. This review summarizes the current data describing the involvement of the Jak-Stat pathway in chemokine-mediated signaling in T lymphocytes and discusses the potential crosstalk with other TCR and cytokine-mediated signaling pathways.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"36 3","pages":"427-438"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200700144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Through interaction with G protein-coupled receptors, histamine regulates pre- and post-synaptically a number of brain functions such as wakefulness, locomotor activity, autonomic and vestibular functions, feeding, drinking, analgesia and memory. Four such receptors have been cloned to date, and three of them (H1, H2, and H3) are widely distributed in the central nervous system, which contains the great majority of histamine H3 receptors (H3Rs). These receptors are expressed at high densities in the basal ganglia, a group of subcortical neuronal nuclei intimately involved in the regulation of posture and movement. In this review the main characteristics of H3Rs (structure, isoforms, constitutive activity and signaling) are briefly described, to then summarize our own work regarding the H3R-mediated regulation of synaptic transmission in the basal ganglia. Finally, the possible participation of H3Rs in the pathophysiology of Parkinson's disease is discussed. Based on the information herein reviewed it is concluded that H3Rs play a relevant role in basal ganglia function both in normal and pathological conditions, and that H3R agonists and antagonists may have potential use in the treatment of both Parkinson's disease and the complications of the current pharmacological therapies of the disorder.
{"title":"Histamine H3 receptors and their role in basal ganglia physiology and pathophysiology","authors":"J. Arias-Montaño","doi":"10.1002/SITA.200700139","DOIUrl":"https://doi.org/10.1002/SITA.200700139","url":null,"abstract":"Through interaction with G protein-coupled receptors, histamine regulates pre- and post-synaptically a number of brain functions such as wakefulness, locomotor activity, autonomic and vestibular functions, feeding, drinking, analgesia and memory. Four such receptors have been cloned to date, and three of them (H1, H2, and H3) are widely distributed in the central nervous system, which contains the great majority of histamine H3 receptors (H3Rs). These receptors are expressed at high densities in the basal ganglia, a group of subcortical neuronal nuclei intimately involved in the regulation of posture and movement. In this review the main characteristics of H3Rs (structure, isoforms, constitutive activity and signaling) are briefly described, to then summarize our own work regarding the H3R-mediated regulation of synaptic transmission in the basal ganglia. Finally, the possible participation of H3Rs in the pathophysiology of Parkinson's disease is discussed. Based on the information herein reviewed it is concluded that H3Rs play a relevant role in basal ganglia function both in normal and pathological conditions, and that H3R agonists and antagonists may have potential use in the treatment of both Parkinson's disease and the complications of the current pharmacological therapies of the disorder.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"23 1","pages":"364-371"},"PeriodicalIF":0.0,"publicationDate":"2007-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200700139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The pombe Cdc15 homology (PCH) protein family (also termed FCH/SH3 family) comprises 5 subgroups of structurally related polypeptides. The protein kinase C and casein kinase substrate in neurons 1 (PACSIN1), the CD2-binding protein 1 (CD2BP1) and the Cdc42-interacting protein 4 (CIP4) represent members of three individual subgroups. PCH proteins in general are supposed to link cytoskeletal elements to membrane trafficking machineries. In various cellular systems, PCH proteins are involved in lysosomal targeting, vesicular transport, and endocytotic as well as exocytotic processes. However, the specific molecular networks around individual PCH proteins and their localization in different cell populations need to be identified. We have recently reported that several members of the PCH family interact with the death factor FasL (CD178). This interaction is mediated via the SH3 domains of PCH proteins binding to the proline-rich cytoplasmatic region of FasL. To analyze the role of endogenous PCH proteins in the context of FasL or other interactors, novel molecular tools are needed. We developed a set of monoclonal antibodies against three individual PCH family members. These novel reagents will help to analyze the presence and function of endogenous PCH proteins in lymphocytes and other cell types.
{"title":"Novel monoclonal antibodies for the investigation of PCH family proteins","authors":"M. Lettau, A. Beyer, O. Janssen","doi":"10.1002/SITA.200600130","DOIUrl":"https://doi.org/10.1002/SITA.200600130","url":null,"abstract":"The pombe Cdc15 homology (PCH) protein family (also termed FCH/SH3 family) comprises 5 subgroups of structurally related polypeptides. The protein kinase C and casein kinase substrate in neurons 1 (PACSIN1), the CD2-binding protein 1 (CD2BP1) and the Cdc42-interacting protein 4 (CIP4) represent members of three individual subgroups. PCH proteins in general are supposed to link cytoskeletal elements to membrane trafficking machineries. In various cellular systems, PCH proteins are involved in lysosomal targeting, vesicular transport, and endocytotic as well as exocytotic processes. However, the specific molecular networks around individual PCH proteins and their localization in different cell populations need to be identified. We have recently reported that several members of the PCH family interact with the death factor FasL (CD178). This interaction is mediated via the SH3 domains of PCH proteins binding to the proline-rich cytoplasmatic region of FasL. To analyze the role of endogenous PCH proteins in the context of FasL or other interactors, novel molecular tools are needed. We developed a set of monoclonal antibodies against three individual PCH family members. These novel reagents will help to analyze the presence and function of endogenous PCH proteins in lymphocytes and other cell types.","PeriodicalId":88702,"journal":{"name":"Signal transduction","volume":"131 S4","pages":"320-328"},"PeriodicalIF":0.0,"publicationDate":"2007-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/SITA.200600130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50951101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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