Pub Date : 2023-12-13DOI: 10.1093/function/zqad068
Hemalatha Bhagavan, Nicholas J. Burgraff, J. Ramirez
{"title":"Temporal Dynamics and Therapeutic Implications of Phrenic Long-Term Facilitation in Respiratory Control","authors":"Hemalatha Bhagavan, Nicholas J. Burgraff, J. Ramirez","doi":"10.1093/function/zqad068","DOIUrl":"https://doi.org/10.1093/function/zqad068","url":null,"abstract":"","PeriodicalId":12588,"journal":{"name":"Function","volume":"18 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139005316","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}
Pub Date : 2023-12-08DOI: 10.1093/function/zqad067
Julia Gerasimenko, Oleg Gerasimenko
{"title":"Ca2+ Signaling and ATP Production in Pancreatic Cancer","authors":"Julia Gerasimenko, Oleg Gerasimenko","doi":"10.1093/function/zqad067","DOIUrl":"https://doi.org/10.1093/function/zqad067","url":null,"abstract":"","PeriodicalId":12588,"journal":{"name":"Function","volume":"82 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138586720","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}
Pub Date : 2023-12-07DOI: 10.1093/function/zqad069
Sayuri Suzuki, Clay Wakano, Mahealani K. Monteilh-Zoller, Aaron J Cullen, A. Fleig, R. Penner
Cannabinoids are a major class of compounds produced by the plant Cannabis sativa. The most studied of these phytocannabinoids are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). Previous work has demonstrated some therapeutic effects of cannabinoids on pain, inflammation, epilepsy, and chemotherapy-induced nausea and vomiting. However, the precise mechanisms of action of these cannabinoids remain poorly understood. While in most cannabis plant varieties CBD and THC represent the two major cannabinoids, other varieties—referred to as hemp—lack the enzymatic activity to produce significant amounts of THC and mainly produce CBD. Some hemp varieties additionally lack the enzymatic activity to produce CBD, resulting in a plant in which the main molecular cannabinoid species is cannabigerolic acid (CBGA). We recently reported that CBGA has a potent inhibitory effect on both Store-Operated Calcium Entry (SOCE) via inhibition Calcium Release-Activated Calcium (CRAC) channels as well as the channel-kinase TRPM7. Importantly, CBGA prevented kidney damage and suppressed mRNA expression of inflammatory cytokines through inhibition of these mechanisms in an acute nephropathic mouse model. In this study, we comprehensively investigated the most common major and minor cannabinoids to determine their potential efficacy on TRPM7 channel function. Here, we found that approximately half of the cannabinoids tested suppressed TRPM7 currents to some degree, with CBGA having the strongest inhibitory effect on TRPM7. We determined that the CBGA-mediated inhibition of TRPM7 requires a functional kinase domain, is sensitized by both intracellular Mg⋅ATP and free Mg2+, and reduced by increases in intracellular Ca2+. Finally, we demonstrate that CBGA inhibits native TRPM7 in B lymphocytes cell line. In conclusion, we demonstrate that CBGA is the most potent cannabinoid in suppressing TRPM7 activity and possesses the potential to be a pharmacologic therapeutic for diseases in which TRPM7 is known to play an important role such as cancer, stroke, and kidney disease.
{"title":"Cannabigerolic Acid (CBGA) inhibits the TRPM7 ion channel through its kinase domain","authors":"Sayuri Suzuki, Clay Wakano, Mahealani K. Monteilh-Zoller, Aaron J Cullen, A. Fleig, R. Penner","doi":"10.1093/function/zqad069","DOIUrl":"https://doi.org/10.1093/function/zqad069","url":null,"abstract":"\u0000 Cannabinoids are a major class of compounds produced by the plant Cannabis sativa. The most studied of these phytocannabinoids are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). Previous work has demonstrated some therapeutic effects of cannabinoids on pain, inflammation, epilepsy, and chemotherapy-induced nausea and vomiting. However, the precise mechanisms of action of these cannabinoids remain poorly understood. While in most cannabis plant varieties CBD and THC represent the two major cannabinoids, other varieties—referred to as hemp—lack the enzymatic activity to produce significant amounts of THC and mainly produce CBD. Some hemp varieties additionally lack the enzymatic activity to produce CBD, resulting in a plant in which the main molecular cannabinoid species is cannabigerolic acid (CBGA). We recently reported that CBGA has a potent inhibitory effect on both Store-Operated Calcium Entry (SOCE) via inhibition Calcium Release-Activated Calcium (CRAC) channels as well as the channel-kinase TRPM7. Importantly, CBGA prevented kidney damage and suppressed mRNA expression of inflammatory cytokines through inhibition of these mechanisms in an acute nephropathic mouse model. In this study, we comprehensively investigated the most common major and minor cannabinoids to determine their potential efficacy on TRPM7 channel function. Here, we found that approximately half of the cannabinoids tested suppressed TRPM7 currents to some degree, with CBGA having the strongest inhibitory effect on TRPM7. We determined that the CBGA-mediated inhibition of TRPM7 requires a functional kinase domain, is sensitized by both intracellular Mg⋅ATP and free Mg2+, and reduced by increases in intracellular Ca2+. Finally, we demonstrate that CBGA inhibits native TRPM7 in B lymphocytes cell line. In conclusion, we demonstrate that CBGA is the most potent cannabinoid in suppressing TRPM7 activity and possesses the potential to be a pharmacologic therapeutic for diseases in which TRPM7 is known to play an important role such as cancer, stroke, and kidney disease.","PeriodicalId":12588,"journal":{"name":"Function","volume":"32 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138594190","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}
Abstract We have studied the role of the intestine, kidney, and several hormones when adapting to changes in dietary P concentration. Normal and parathyroidectomized (PTX) rats were fed pH-matched diets containing 0.1%, 0.6%, and 1.2% P concentrations. 32Pi uptake was determined in jejunum and kidney cortex brush border membrane vesicles. Several hormone and ion concentrations were determined in the blood and urine of rats. Both jejunum and kidney cortex Pi transport was regulated with 5 days of chronic feeding of P diets in normal rats. Acute adaptation was determined by switching foods on day six, which was only clearly observed in the kidney cortex of normal rats, with more statistical variability in the jejunum. However, no paradoxical increase of Pi uptake in the jejunum was reproduced after the acute switch to the 1.2% P diet. Pi uptake in the jejunum was PTH-independent, but in the kidney, the chronic adaptation was reduced, and no acute dietary adaptations were observed. The NaPi2a protein was more abundant in the PTX than the sham kidneys, but contrary to the modest or absent changes in Pi uptake adaptation, the transporter was similarly regulated by dietary P, as in the sham rats. PTH and FGF23 were the only hormones regulated by all diet changes, even in fasting animals, which exhibited regulated Pi transport despite similar phosphatemia. Evidence of Pi appetite effects was also observed. In brief, our results show new characteristics of Pi adaptations, including a lack of correlation between Pi transport, NaPi2a expression, and PTH/FGF23 concentrations.
{"title":"Intestinal and Renal Adaptations to Changes of Dietary Phosphate Concentrations in Rat","authors":"Susana Lucea, Gema Chopo-Escuin, Natalia Guillén, Cecilia Sosa, Víctor Sorribas","doi":"10.1093/function/zqad063","DOIUrl":"https://doi.org/10.1093/function/zqad063","url":null,"abstract":"Abstract We have studied the role of the intestine, kidney, and several hormones when adapting to changes in dietary P concentration. Normal and parathyroidectomized (PTX) rats were fed pH-matched diets containing 0.1%, 0.6%, and 1.2% P concentrations. 32Pi uptake was determined in jejunum and kidney cortex brush border membrane vesicles. Several hormone and ion concentrations were determined in the blood and urine of rats. Both jejunum and kidney cortex Pi transport was regulated with 5 days of chronic feeding of P diets in normal rats. Acute adaptation was determined by switching foods on day six, which was only clearly observed in the kidney cortex of normal rats, with more statistical variability in the jejunum. However, no paradoxical increase of Pi uptake in the jejunum was reproduced after the acute switch to the 1.2% P diet. Pi uptake in the jejunum was PTH-independent, but in the kidney, the chronic adaptation was reduced, and no acute dietary adaptations were observed. The NaPi2a protein was more abundant in the PTX than the sham kidneys, but contrary to the modest or absent changes in Pi uptake adaptation, the transporter was similarly regulated by dietary P, as in the sham rats. PTH and FGF23 were the only hormones regulated by all diet changes, even in fasting animals, which exhibited regulated Pi transport despite similar phosphatemia. Evidence of Pi appetite effects was also observed. In brief, our results show new characteristics of Pi adaptations, including a lack of correlation between Pi transport, NaPi2a expression, and PTH/FGF23 concentrations.","PeriodicalId":12588,"journal":{"name":"Function","volume":"133 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136351832","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}
Pub Date : 2023-11-06DOI: 10.1093/function/zqad062
Ahmed Ismaeel, Nicholas T Thomas, Mariah McCashland, Ivan J Vechetti, Sebastian Edman, Johanna T Lanner, Vandré C Figueiredo, Christopher S Fry, John J McCarthy, Yuan Wen, Kevin A Murach, Ferdinand von Walden
Abstract The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature miRNA and other small RNA species provides new directions for exploring muscle adaptation and complemented the methylation and transcriptional information. Our integrated multi-omics interrogation revealed a coordinated myonuclear molecular landscape during muscle loading that coincides with an acute and rapid reduction of oxidative metabolism. This response may favor a biosynthesis-oriented metabolic program that supports rapid hypertrophic growth.
{"title":"Coordinated Regulation of Myonuclear DNA Methylation, mRNA, And miRNA Levels Associates with The Metabolic Response to Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy in Female Mice","authors":"Ahmed Ismaeel, Nicholas T Thomas, Mariah McCashland, Ivan J Vechetti, Sebastian Edman, Johanna T Lanner, Vandré C Figueiredo, Christopher S Fry, John J McCarthy, Yuan Wen, Kevin A Murach, Ferdinand von Walden","doi":"10.1093/function/zqad062","DOIUrl":"https://doi.org/10.1093/function/zqad062","url":null,"abstract":"Abstract The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature miRNA and other small RNA species provides new directions for exploring muscle adaptation and complemented the methylation and transcriptional information. Our integrated multi-omics interrogation revealed a coordinated myonuclear molecular landscape during muscle loading that coincides with an acute and rapid reduction of oxidative metabolism. This response may favor a biosynthesis-oriented metabolic program that supports rapid hypertrophic growth.","PeriodicalId":12588,"journal":{"name":"Function","volume":"160 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135723656","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}
Abstract Modern neuroscience is progressively elucidating that the classic view positing distinct brain regions responsible for survival, emotion, and cognitive functions is outdated. The hypothalamus demonstrates the interdependence of these roles, as it's traditionally known for fundamental survival functions like energy and electrolyte balance, but is now recognized to also play a crucial role in emotional and cognitive processes. This review focuses on lateral hypothalamic MCH neurons, producing the neuropeptide melanin concentrating hormone (MCH)—a relatively understudied neuronal population with integrative functions related to homeostatic regulation and motivated behaviors, with widespread inputs and outputs throughout the entire central nervous system. Here, we review early findings and recent literature outlining their role in the regulation of energy balance, sleep, learning and memory processes.
{"title":"Hypothalamic MCH neurons: from feeding to cognitive control","authors":"Cristina Concetti, Daria Peleg-Raibstein, Denis Burdakov","doi":"10.1093/function/zqad059","DOIUrl":"https://doi.org/10.1093/function/zqad059","url":null,"abstract":"Abstract Modern neuroscience is progressively elucidating that the classic view positing distinct brain regions responsible for survival, emotion, and cognitive functions is outdated. The hypothalamus demonstrates the interdependence of these roles, as it's traditionally known for fundamental survival functions like energy and electrolyte balance, but is now recognized to also play a crucial role in emotional and cognitive processes. This review focuses on lateral hypothalamic MCH neurons, producing the neuropeptide melanin concentrating hormone (MCH)—a relatively understudied neuronal population with integrative functions related to homeostatic regulation and motivated behaviors, with widespread inputs and outputs throughout the entire central nervous system. Here, we review early findings and recent literature outlining their role in the regulation of energy balance, sleep, learning and memory processes.","PeriodicalId":12588,"journal":{"name":"Function","volume":"19 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136234691","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}
Pub Date : 2023-10-23DOI: 10.1093/function/zqad061
Mengya Niu, Xiuli Zhang, Zengkai Wu, Bin Li, Jingpiao Bao, Juanjuan Dai, Zihan Yang, Yue Zeng, Liang Li, Stephen Pandol, Robert Sutton, Li Wen
Abstract Acute pancreatitis is initiated within pancreatic exocrine cells and sustained by dysregulated systemic inflammatory responses mediated by neutrophils. Store-operated Ca2+ entry (SOCE) through ORAI1 channels in pancreatic acinar cells triggers acute pancreatitis, and ORAI1 inhibitors ameliorate experimental acute pancreatitis, but the role of ORAI1 in pancreatitis-associated acute lung injury has not been determined. Here, we showed mice with pancreas-specific deletion of Orai1 (Orai1ΔPdx1, ∼70% reduction in the expression of Orai1) are protected against pancreatic tissue damage and immune cell infiltration, but not pancreatitis-associated acute lung injury, suggesting the involvement of unknown cells that may cause such injury through SOCE via ORAI1. Genetic (Orai1ΔMRP8) or pharmacological inhibition of ORAI1 in murine and human neutrophils decreased Ca2+ influx and impaired chemotaxis, reactive oxygen species production and neutrophil extracellular trap formation. Unlike pancreas-specific Orai1 deletion, mice with neutrophil-specific deletion of Orai1 (Orai1ΔMRP8) were protected against pancreatitis- and sepsis-associated lung cytokine release and injury, but not pancreatic injury in experimental acute pancreatitis. These results define critical differences between contributions from different cell types to either pancreatic or systemic organ injury in acute pancreatitis. Our findings suggest that any therapy for acute pancreatitis that targets multiple rather than single cell types is more likely to be effective.
{"title":"Neutrophil-Specific ORAI1 Calcium Channel Inhibition Reduces Pancreatitis-Associated Acute Lung Injury","authors":"Mengya Niu, Xiuli Zhang, Zengkai Wu, Bin Li, Jingpiao Bao, Juanjuan Dai, Zihan Yang, Yue Zeng, Liang Li, Stephen Pandol, Robert Sutton, Li Wen","doi":"10.1093/function/zqad061","DOIUrl":"https://doi.org/10.1093/function/zqad061","url":null,"abstract":"Abstract Acute pancreatitis is initiated within pancreatic exocrine cells and sustained by dysregulated systemic inflammatory responses mediated by neutrophils. Store-operated Ca2+ entry (SOCE) through ORAI1 channels in pancreatic acinar cells triggers acute pancreatitis, and ORAI1 inhibitors ameliorate experimental acute pancreatitis, but the role of ORAI1 in pancreatitis-associated acute lung injury has not been determined. Here, we showed mice with pancreas-specific deletion of Orai1 (Orai1ΔPdx1, ∼70% reduction in the expression of Orai1) are protected against pancreatic tissue damage and immune cell infiltration, but not pancreatitis-associated acute lung injury, suggesting the involvement of unknown cells that may cause such injury through SOCE via ORAI1. Genetic (Orai1ΔMRP8) or pharmacological inhibition of ORAI1 in murine and human neutrophils decreased Ca2+ influx and impaired chemotaxis, reactive oxygen species production and neutrophil extracellular trap formation. Unlike pancreas-specific Orai1 deletion, mice with neutrophil-specific deletion of Orai1 (Orai1ΔMRP8) were protected against pancreatitis- and sepsis-associated lung cytokine release and injury, but not pancreatic injury in experimental acute pancreatitis. These results define critical differences between contributions from different cell types to either pancreatic or systemic organ injury in acute pancreatitis. Our findings suggest that any therapy for acute pancreatitis that targets multiple rather than single cell types is more likely to be effective.","PeriodicalId":12588,"journal":{"name":"Function","volume":"29 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135413137","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}
Pub Date : 2023-10-19DOI: 10.1093/function/zqad060
Shehrazade Dahimene, Karen M Page, Manuela Nieto-Rostro, Wendy S Pratt, Annette C Dolphin
Abstract N-type calcium channels (CaV2.2) are predominantly localized in presynaptic terminals, and are particularly important for pain transmission in the spinal cord. Furthermore, they have multiple isoforms, conferred by alternatively-spliced or cassette exons, which are differentially expressed. Here we have examined alternatively-spliced exon47 variants that encode a long or short C-terminus in human CaV2.2. In the Ensembl database, all short exon47-containing transcripts were associated with the absence of exon 18a, therefore we also examined effect of inclusion or absence of exon18a, combinatorially with the exon47 splice variants. We found that long exon47, only in the additional presence of exon18a, results in CaV2.2 currents that have a 3.6-fold greater maximum conductance than the other three combinations. In contrast, cell surface expression of CaV2.2 in both tsA-201 cells and hippocampal neurons is increased ∼4-fold by long exon47, relative to short exon47, in either the presence or absence of exon18a. This surprising discrepancy between trafficking and function indicates that cell surface expression is enhanced by long exon47, independently of exon 18a. However, in the presence of exon47, exon18a mediates an additional permissive effect on CaV2.2 gating. We also investigated the SNP in exon47 that has been linked to schizophrenia and Parkinson's disease, which we found is only non-synonymous in the short exon47 C-terminal isoform, resulting in two minor alleles. This study highlights the importance of investigating the combinatorial effects of exon inclusion, rather than each in isolation, in order to increase our understanding of calcium channel function.
{"title":"The Interplay Between Splicing of Two Exon Combinations Differentially Affects Membrane Targeting And Function of Human CaV2.2","authors":"Shehrazade Dahimene, Karen M Page, Manuela Nieto-Rostro, Wendy S Pratt, Annette C Dolphin","doi":"10.1093/function/zqad060","DOIUrl":"https://doi.org/10.1093/function/zqad060","url":null,"abstract":"Abstract N-type calcium channels (CaV2.2) are predominantly localized in presynaptic terminals, and are particularly important for pain transmission in the spinal cord. Furthermore, they have multiple isoforms, conferred by alternatively-spliced or cassette exons, which are differentially expressed. Here we have examined alternatively-spliced exon47 variants that encode a long or short C-terminus in human CaV2.2. In the Ensembl database, all short exon47-containing transcripts were associated with the absence of exon 18a, therefore we also examined effect of inclusion or absence of exon18a, combinatorially with the exon47 splice variants. We found that long exon47, only in the additional presence of exon18a, results in CaV2.2 currents that have a 3.6-fold greater maximum conductance than the other three combinations. In contrast, cell surface expression of CaV2.2 in both tsA-201 cells and hippocampal neurons is increased ∼4-fold by long exon47, relative to short exon47, in either the presence or absence of exon18a. This surprising discrepancy between trafficking and function indicates that cell surface expression is enhanced by long exon47, independently of exon 18a. However, in the presence of exon47, exon18a mediates an additional permissive effect on CaV2.2 gating. We also investigated the SNP in exon47 that has been linked to schizophrenia and Parkinson's disease, which we found is only non-synonymous in the short exon47 C-terminal isoform, resulting in two minor alleles. This study highlights the importance of investigating the combinatorial effects of exon inclusion, rather than each in isolation, in order to increase our understanding of calcium channel function.","PeriodicalId":12588,"journal":{"name":"Function","volume":"69 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135780401","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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