The humoral immune response, alongside cell-mediated immunity, in which B cells play a key role, form the primary arms of the adaptive immune system. Resting mature follicular (FO) B cells in the spleen are essential for antibody-mediated immune responses. They recirculate through the blood, and are activated upon the binding of various diverse cognate antigens to the specific B cell antigen receptor (BCR) on their cell surface. With the help of T cells, the activated FO B cells undergo the germinal center (GC) reaction, which involves massive expansion and immunoglobulin (Ig) class-switch recombination (e.g. IgM to IgG1) to elicit a high-affinity antibody response against the antigens. Zinc (Zn) is essential in immunity, and in both humans and rodents, aberrant Zn homeostasis strongly disrupts the cellularity and functions of immune cells, leading to thymic and splenic atrophy, lymphopenia, and weakened cellular and humoral immunity, which increases the host’s susceptibility to various pathogens. Zn, which is transported by specific members of the Zn-transporter families, SLC39/ZIP and SLC30/ZnT, selectively fine-tunes distinct intracellular signaling events by targeting signaling molecules involved in development, growth, and immunity. Zn controls a wide range of immune signaling cascades that lead to cytokine production, antigen presentation, and the activation of kinases and transcription factors in immune cells, and disrupting the specific Zn transporter−Zn signal axis impairs cellular function. However, how Zn controls immune function, in particular the humoral immune response, is poorly understood. In this research highlight, we review our recent finding that ZIP10-Zn signaling is required in B-cell receptor signaling for the antibody-mediated immune response.
{"title":"B-cell receptor strength and zinc signaling: Unraveling the role of zinc transporter ZIP10 in humoral immunity","authors":"Shintaro Hojyo, T. Miyai, T. Fukada","doi":"10.14800/RCI.387","DOIUrl":"https://doi.org/10.14800/RCI.387","url":null,"abstract":"The humoral immune response, alongside cell-mediated immunity, in which B cells play a key role, form the primary arms of the adaptive immune system. Resting mature follicular (FO) B cells in the spleen are essential for antibody-mediated immune responses. They recirculate through the blood, and are activated upon the binding of various diverse cognate antigens to the specific B cell antigen receptor (BCR) on their cell surface. With the help of T cells, the activated FO B cells undergo the germinal center (GC) reaction, which involves massive expansion and immunoglobulin (Ig) class-switch recombination (e.g. IgM to IgG1) to elicit a high-affinity antibody response against the antigens. Zinc (Zn) is essential in immunity, and in both humans and rodents, aberrant Zn homeostasis strongly disrupts the cellularity and functions of immune cells, leading to thymic and splenic atrophy, lymphopenia, and weakened cellular and humoral immunity, which increases the host’s susceptibility to various pathogens. Zn, which is transported by specific members of the Zn-transporter families, SLC39/ZIP and SLC30/ZnT, selectively fine-tunes distinct intracellular signaling events by targeting signaling molecules involved in development, growth, and immunity. Zn controls a wide range of immune signaling cascades that lead to cytokine production, antigen presentation, and the activation of kinases and transcription factors in immune cells, and disrupting the specific Zn transporter−Zn signal axis impairs cellular function. However, how Zn controls immune function, in particular the humoral immune response, is poorly understood. In this research highlight, we review our recent finding that ZIP10-Zn signaling is required in B-cell receptor signaling for the antibody-mediated immune response.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"88 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85318564","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}
To investigate fundamental processes conserved in all eukaryotic cells, the budding yeast Saccharomyces cerevisiae has being widely used as a model organism. In particular, the yeast two-hybrid system is a powerful technique for analyzing protein–protein interactions and protein function in living cells. Here, we describe several approaches for investigating and regulating the activity of target proteins using the yeast guanine nucleotide-binding protein (G-protein) signaling machinery as the readout. These approaches are rapid and easy-to-use tools that support the design of regulatory factors against receptors, enzymes, and other proteins that have been identified as potential drug target molecules.
{"title":"Functional analyses and affinity-alteration of receptors and enzymes based on membrane recruitment of yeast guanine nucleotide-binding protein gamma subunit","authors":"Nobuo Fukuda, S. Honda","doi":"10.14800/RCI.373","DOIUrl":"https://doi.org/10.14800/RCI.373","url":null,"abstract":"To investigate fundamental processes conserved in all eukaryotic cells, the budding yeast Saccharomyces cerevisiae has being widely used as a model organism. In particular, the yeast two-hybrid system is a powerful technique for analyzing protein–protein interactions and protein function in living cells. Here, we describe several approaches for investigating and regulating the activity of target proteins using the yeast guanine nucleotide-binding protein (G-protein) signaling machinery as the readout. These approaches are rapid and easy-to-use tools that support the design of regulatory factors against receptors, enzymes, and other proteins that have been identified as potential drug target molecules.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89323223","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}
Obesity, which is triggered by over-nutrition and supported by the excessive expansion of adipose tissue due to hyperplasia and hypertrophy, has been linked to an increased incidence of type 2 diabetes, hypertension, cardiovascular disease and cancer. Since obesity-induced co-morbidities impose a significant financial burden on healthcare systems in Western societies, clear understanding of molecules and mechanisms supporting physiologic and pathologic activities of adipose tissue is mandatory. Abundant evidence shows that development of obesity is facilitated by a low-grade inflammation fueled by infiltration of pro-inflammatory leukocytes into white adipose tissue pads, which is in part mediated by chemokines and chemokine receptors. However, not all members of the chemokine system facilitate development of obesity. In this publication we highlight a surprising role of CXCR4 in fat cells where this chemokine receptor promotes energy expenditure and prevents excessive inflammatory leukocyte recruitment into adipose tissue, and by so doing, limits obesity.
{"title":"Chemokine receptors on the defensive - the surprising role of CXCR4 in brown adipose tissue","authors":"L. Yao, Janet Heuser-Baker, Jana Barlic-Dicen","doi":"10.14800/RCI.397","DOIUrl":"https://doi.org/10.14800/RCI.397","url":null,"abstract":"Obesity, which is triggered by over-nutrition and supported by the excessive expansion of adipose tissue due to hyperplasia and hypertrophy, has been linked to an increased incidence of type 2 diabetes, hypertension, cardiovascular disease and cancer. Since obesity-induced co-morbidities impose a significant financial burden on healthcare systems in Western societies, clear understanding of molecules and mechanisms supporting physiologic and pathologic activities of adipose tissue is mandatory. Abundant evidence shows that development of obesity is facilitated by a low-grade inflammation fueled by infiltration of pro-inflammatory leukocytes into white adipose tissue pads, which is in part mediated by chemokines and chemokine receptors. However, not all members of the chemokine system facilitate development of obesity. In this publication we highlight a surprising role of CXCR4 in fat cells where this chemokine receptor promotes energy expenditure and prevents excessive inflammatory leukocyte recruitment into adipose tissue, and by so doing, limits obesity.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79433560","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 regulation mechanism of peroxisome proliferator-activated receptor g (PPARg) known as key determinant in adipogenesis is important for understanding the cause of lipid metabolic disorders and glucose metabolic syndromes. In a recent paper published in Journal of Cell Science, we demonstrated that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a novel negative regulator of PPARg. Although AIMP1 is originally found as a factor associated with multi-tRNA synthetase complex for translation, it has been shown to play regulatory roles in diverse cellular processes. Now AIMP1 is shown to negatively regulates PPARg-mediated transcription through direct interaction with DNA-binding domain of PPARg and inhibits adipogenesis. These results suggest that AIMP1 functions as a novel inhibitor of PPARg, raising the possible linkage between translation and adipogenesis.
{"title":"AIMP1 negatively regulates PPARgamma: Implication in adipogenesis","authors":"J. H. Kim, J. Han, Sunghoon Kim","doi":"10.14800/RCI.377","DOIUrl":"https://doi.org/10.14800/RCI.377","url":null,"abstract":"The regulation mechanism of peroxisome proliferator-activated receptor g (PPARg) known as key determinant in adipogenesis is important for understanding the cause of lipid metabolic disorders and glucose metabolic syndromes. In a recent paper published in Journal of Cell Science, we demonstrated that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a novel negative regulator of PPARg. Although AIMP1 is originally found as a factor associated with multi-tRNA synthetase complex for translation, it has been shown to play regulatory roles in diverse cellular processes. Now AIMP1 is shown to negatively regulates PPARg-mediated transcription through direct interaction with DNA-binding domain of PPARg and inhibits adipogenesis. These results suggest that AIMP1 functions as a novel inhibitor of PPARg, raising the possible linkage between translation and adipogenesis.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74586627","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}
Oseltamivir (Tamiflu) effectively inhibits influenza virus-specific neuraminidase and therefore, is widely prescribed as an anti-influenza medication. Although a wide safety margin of oseltamivir has been reported, the possible neuronal adverse effects of this drug via unknown mechanisms are shown in some studies: dyskinesia, depressive episodes, hypothermia, and other CNS dysfunctions. We therefore, examined effects of oseltamivir on human nicotinic acetylcholine (ACh) receptors (nAChRs) with electrophysiological methods and found that oseltamivir reversely blocks nicotine- and ACh-evoked membrane currents in a concentration dependent manner in neuroblastoma cells derived from human peripheral neurons (IMR32) and in HEK cells expressing recombinant human α3β4 nAChRs. In contrast, an active metabolite of oseltamivir, oseltamivir carboxylate (OC) had little effect on the nicotine-evoked currents. Moreover, single channel analysis revealed that oseltamivir reduces the channel open time of nAChR without affecting the channel conductance. Our results demonstrate that human α3β4 nAChRs are a potential pharmacological target of oseltamivir, hence explaining a part of the adverse effects after ingestion of oseltamivir.
{"title":"Human nicotinic acetylcholine receptor is a potential pharmacological target of oseltamivir","authors":"K. Muraki, H. Ono","doi":"10.14800/RCI.360","DOIUrl":"https://doi.org/10.14800/RCI.360","url":null,"abstract":"Oseltamivir (Tamiflu) effectively inhibits influenza virus-specific neuraminidase and therefore, is widely prescribed as an anti-influenza medication. Although a wide safety margin of oseltamivir has been reported, the possible neuronal adverse effects of this drug via unknown mechanisms are shown in some studies: dyskinesia, depressive episodes, hypothermia, and other CNS dysfunctions. We therefore, examined effects of oseltamivir on human nicotinic acetylcholine (ACh) receptors (nAChRs) with electrophysiological methods and found that oseltamivir reversely blocks nicotine- and ACh-evoked membrane currents in a concentration dependent manner in neuroblastoma cells derived from human peripheral neurons (IMR32) and in HEK cells expressing recombinant human α3β4 nAChRs. In contrast, an active metabolite of oseltamivir, oseltamivir carboxylate (OC) had little effect on the nicotine-evoked currents. Moreover, single channel analysis revealed that oseltamivir reduces the channel open time of nAChR without affecting the channel conductance. Our results demonstrate that human α3β4 nAChRs are a potential pharmacological target of oseltamivir, hence explaining a part of the adverse effects after ingestion of oseltamivir.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91019104","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}
Aliskiren, a direct renin inhibitor, blocks the first step of the renin–angiotensin–aldosterone system (RAAS), thereby reducing plasma renin activity and the circulating levels of angiotensin I, angiotensin II, and aldosterone. Extensive RAAS blockade can be achieved through the administration of aliskiren; however, renin blockade is a double-edged sword because the renin/prorenin receptor-associated pathway is also reportedly modulated by direct renin inhibitor. This research highlight discusses the findings of a recent clinical study of aliskiren and explores the complex interactions of key molecules in the RAAS pathway in response to aliskiren administration.
{"title":"Renin blockade: a double-edged sword?","authors":"E. Amiya, A. Ozeki, Masafumi Watanabe","doi":"10.14800/RCI.357","DOIUrl":"https://doi.org/10.14800/RCI.357","url":null,"abstract":"Aliskiren, a direct renin inhibitor, blocks the first step of the renin–angiotensin–aldosterone system (RAAS), thereby reducing plasma renin activity and the circulating levels of angiotensin I, angiotensin II, and aldosterone. Extensive RAAS blockade can be achieved through the administration of aliskiren; however, renin blockade is a double-edged sword because the renin/prorenin receptor-associated pathway is also reportedly modulated by direct renin inhibitor. This research highlight discusses the findings of a recent clinical study of aliskiren and explores the complex interactions of key molecules in the RAAS pathway in response to aliskiren administration.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83316365","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}
Targeting of ErbB family of receptor tyrosine kinases (RTKs) is frequently used to inhibit the oncogenic signaling in different malignancies. Lapatinib, a dual selective tyrosine kinase inhibitor (TKI) of EGFR and HER2, inhibits their tyrosine kinase activities and receptor tyrosine phosphorylation. Cetuximab, a chimeric monoclonal antibody (mAb) directed against the extracellular domain of EGFR, prevents EGF-mediated receptor kinase activation and tyrosine phosphorylation. However, trastuzumab, a humanized mAb directed against HER2, induces EGFR and HER2 receptor tyrosine phosphorylation and this agonistic effect is correlated with its inhibition of cancer cell proliferation. This review will focus on the current understanding of molecular mechanisms and implications of trastuzumab-induced tyrosine phosphorylation of HER2.
{"title":"Trastuzumab-induced HER2 phosphorylation: exploring the mechanisms and implications","authors":"Milos Dokmanovic, W. J. Wu","doi":"10.14800/RCI.340","DOIUrl":"https://doi.org/10.14800/RCI.340","url":null,"abstract":"Targeting of ErbB family of receptor tyrosine kinases (RTKs) is frequently used to inhibit the oncogenic signaling in different malignancies. Lapatinib, a dual selective tyrosine kinase inhibitor (TKI) of EGFR and HER2, inhibits their tyrosine kinase activities and receptor tyrosine phosphorylation. Cetuximab, a chimeric monoclonal antibody (mAb) directed against the extracellular domain of EGFR, prevents EGF-mediated receptor kinase activation and tyrosine phosphorylation. However, trastuzumab, a humanized mAb directed against HER2, induces EGFR and HER2 receptor tyrosine phosphorylation and this agonistic effect is correlated with its inhibition of cancer cell proliferation. This review will focus on the current understanding of molecular mechanisms and implications of trastuzumab-induced tyrosine phosphorylation of HER2.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84945134","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 concentration of adenosine nucleotides (ATP&ADP) in the circulation may impact health and disease by controlling cellular metabolic pathways in tissues throughout the body. Fasting plasma nucleotide levels are normally relatively low in healthy subjects, but can increase by orders of magnitude in disease. High circulating nucleotide levels promote chronic purinergic signaling, which may disrupt the normal cellular metabolism in the body and initiate immune and inflammatory consequences. Strategies to control nucleotide levels in the bloodstream may therefore have therapeutic importance to halt the progression of metabolic disorders.
{"title":"Circulating Nucleotides in Health and Disease","authors":"D. Sparks, Heather Doelle, Cynthia Chatterjee","doi":"10.14800/RCI.344","DOIUrl":"https://doi.org/10.14800/RCI.344","url":null,"abstract":"The concentration of adenosine nucleotides (ATP&ADP) in the circulation may impact health and disease by controlling cellular metabolic pathways in tissues throughout the body. Fasting plasma nucleotide levels are normally relatively low in healthy subjects, but can increase by orders of magnitude in disease. High circulating nucleotide levels promote chronic purinergic signaling, which may disrupt the normal cellular metabolism in the body and initiate immune and inflammatory consequences. Strategies to control nucleotide levels in the bloodstream may therefore have therapeutic importance to halt the progression of metabolic disorders.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"124 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90080121","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}
Novel insecticidal chiral phthalamides containing N -cyano and N -trifluroacetyl sulfiliminyl moieties were firstly described, coupled with their insecticidal activity against oriental armyworm ( Pseudaletia separata Walker) and diamondback moth ( Plutella xylostella (L.) ). The chirality of carbon and sulfur impact on bioactivity was systemically studied
{"title":"The Study of Novel diamide Insecticides: Chiral Sulfilimines","authors":"Sha Zhou, Zhengming Li","doi":"10.14800/RCI.339","DOIUrl":"https://doi.org/10.14800/RCI.339","url":null,"abstract":"Novel insecticidal chiral phthalamides containing N -cyano and N -trifluroacetyl sulfiliminyl moieties were firstly described, coupled with their insecticidal activity against oriental armyworm ( Pseudaletia separata Walker) and diamondback moth ( Plutella xylostella (L.) ). The chirality of carbon and sulfur impact on bioactivity was systemically studied","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"100 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88095264","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 economic burden associated with preterm birth is significant to our society. While research efforts on preterm birth over past decades had been directed toward understanding the late stage of parturition, recent discoveries have indicated that the timing of labour is delicately programmed as early as the initiation of pregnancy. We have proposed that there exists a myometrium phenotype programming during pregnancy consisting three characteristic stages referred to as the early proliferative, the midterm hypertrophic and the late contractile stages. This remarkable plasticity of myometrium allows it not only provides containment for fetus to be fully developed within the womb during pregnancy, but also performs coordinate contractions at the onset of labor to expel the fetus into extrauterine environment. Our two recent studies further demonstrate that the androgen receptor is a key component of myometrium phenotype programming. Here we summarize our endeavor in characterizing the androgen receptor signaling in myometrial smooth muscle cells.
{"title":"The Androgen Receptor Is a Key Component of Myometrium Phenotype Programming During Pregnancy","authors":"Xuesen Dong","doi":"10.14800/RCI.326","DOIUrl":"https://doi.org/10.14800/RCI.326","url":null,"abstract":"The economic burden associated with preterm birth is significant to our society. While research efforts on preterm birth over past decades had been directed toward understanding the late stage of parturition, recent discoveries have indicated that the timing of labour is delicately programmed as early as the initiation of pregnancy. We have proposed that there exists a myometrium phenotype programming during pregnancy consisting three characteristic stages referred to as the early proliferative, the midterm hypertrophic and the late contractile stages. This remarkable plasticity of myometrium allows it not only provides containment for fetus to be fully developed within the womb during pregnancy, but also performs coordinate contractions at the onset of labor to expel the fetus into extrauterine environment. Our two recent studies further demonstrate that the androgen receptor is a key component of myometrium phenotype programming. Here we summarize our endeavor in characterizing the androgen receptor signaling in myometrial smooth muscle cells.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77476133","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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