Pub Date : 2008-09-25DOI: 10.1895/wormbook.1.142.1
Chris Li, Kyuhyung Kim
The role of neuropeptides in modulating behavior is slowly being elucidated. With the sequencing of the C. elegans genome, the extent of the neuropeptide genes in C. elegans can be determined. To date, 113 neuropeptide genes encoding over 250 distinct neuropeptides have been identified. Of these, 40 genes encode insulin-like peptides, 31 genes encode FMRFamide-related peptides, and 42 genes encode non-insulin, non-FMRFamide-related neuropeptides. As in other systems, C. elegans neuropeptides are derived from precursor molecules that must be post-translationally processed to yield the active peptides. These precursor molecules contain a single peptide, multiple copies of a single peptide, multiple distinct peptides, or any combination thereof. The neuropeptide genes are expressed extensively throughout the nervous system, including in sensory, motor, and interneurons. In addition, some of the genes are also expressed in non-neuronal tissues, such as the somatic gonad, intestine, and vulval hypodermis. To address the effects of neuropeptides on C. elegans behavior, animals in which the different neuropeptide genes are inactivated or overexpressed are being isolated. In a complementary approach the receptors to which the neuropeptides bind are also being identified and examined. Among the knockout animals analyzed thus far, defects in locomotion, dauer formation, egg laying, ethanol response, and social behavior have been reported. These data suggest that neuropeptides have a modulatory role in many, if not all, behaviors in C. elegans.
{"title":"Neuropeptides.","authors":"Chris Li, Kyuhyung Kim","doi":"10.1895/wormbook.1.142.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.142.1","url":null,"abstract":"<p><p>The role of neuropeptides in modulating behavior is slowly being elucidated. With the sequencing of the C. elegans genome, the extent of the neuropeptide genes in C. elegans can be determined. To date, 113 neuropeptide genes encoding over 250 distinct neuropeptides have been identified. Of these, 40 genes encode insulin-like peptides, 31 genes encode FMRFamide-related peptides, and 42 genes encode non-insulin, non-FMRFamide-related neuropeptides. As in other systems, C. elegans neuropeptides are derived from precursor molecules that must be post-translationally processed to yield the active peptides. These precursor molecules contain a single peptide, multiple copies of a single peptide, multiple distinct peptides, or any combination thereof. The neuropeptide genes are expressed extensively throughout the nervous system, including in sensory, motor, and interneurons. In addition, some of the genes are also expressed in non-neuronal tissues, such as the somatic gonad, intestine, and vulval hypodermis. To address the effects of neuropeptides on C. elegans behavior, animals in which the different neuropeptide genes are inactivated or overexpressed are being isolated. In a complementary approach the receptors to which the neuropeptides bind are also being identified and examined. Among the knockout animals analyzed thus far, defects in locomotion, dauer formation, egg laying, ethanol response, and social behavior have been reported. These data suggest that neuropeptides have a modulatory role in many, if not all, behaviors in C. elegans.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1895/wormbook.1.142.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27698428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-09-04DOI: 10.1895/wormbook.1.145.1
Anton Gartner, Peter R Boag, T Keith Blackwell
Germline apoptosis shares with somatic apoptosis a reliance on key components of the core apoptotic machinery, including CED-3 and CED-4. However, germline apoptosis differs from somatic apoptosis in its regulation. Whereas somatic apoptosis is developmentally programmed by cell lineage, germline apoptosis occurs as part of an oogenesis program. One category of germline apoptosis, dubbed "physiological" germline apoptosis, reduces the number of cells that complete oogenesis, and is independent of the BH3-only apoptosis effecter EGL-1. A second category, termed "stress-induced" germline apoptosis, is triggered by a genomic integrity checkpoint. Some mechanisms that are monitored by this DNA-damage checkpoint are also involved in germ cell "immortality," or preservation of a continuous germ cell lineage over successive generations. In addition, exposure to certain environmental insults or pathogens induces germ cell apoptosis. Here we will review the mechanisms that control each of the pathways leading to germ cell apoptosis and discuss their functional significance. Germline apoptosis is an integral part of oogenesis in many animals, including humans. Because many of the regulators of C. elegans germline apoptosis are conserved, we suggest that this nematode provides a valuable model for understanding controls of germline apoptosis more broadly.
{"title":"Germline survival and apoptosis.","authors":"Anton Gartner, Peter R Boag, T Keith Blackwell","doi":"10.1895/wormbook.1.145.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.145.1","url":null,"abstract":"<p><p>Germline apoptosis shares with somatic apoptosis a reliance on key components of the core apoptotic machinery, including CED-3 and CED-4. However, germline apoptosis differs from somatic apoptosis in its regulation. Whereas somatic apoptosis is developmentally programmed by cell lineage, germline apoptosis occurs as part of an oogenesis program. One category of germline apoptosis, dubbed \"physiological\" germline apoptosis, reduces the number of cells that complete oogenesis, and is independent of the BH3-only apoptosis effecter EGL-1. A second category, termed \"stress-induced\" germline apoptosis, is triggered by a genomic integrity checkpoint. Some mechanisms that are monitored by this DNA-damage checkpoint are also involved in germ cell \"immortality,\" or preservation of a continuous germ cell lineage over successive generations. In addition, exposure to certain environmental insults or pathogens induces germ cell apoptosis. Here we will review the mechanisms that control each of the pathways leading to germ cell apoptosis and discuss their functional significance. Germline apoptosis is an integral part of oogenesis in many animals, including humans. Because many of the regulators of C. elegans germline apoptosis are conserved, we suggest that this nematode provides a valuable model for understanding controls of germline apoptosis more broadly.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27666540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-24DOI: 10.1895/wormbook.1.137.1
James J Collins, Cheng Huang, Stacie Hughes, Kerry Kornfeld
Aging is characterized by progressive degenerative changes in tissue organization and function that increase the probability of mortality. Major goals of aging research include elucidating the series of events that cause degenerative changes and analyzing environmental and genetic factors that modulate these changes. The basis for mechanistic studies of aging are accurate and precise descriptions of age-related changes, since these descriptions define the aging phenotype. Here we review studies that describe age-related changes in C. elegans including measurements of integrated functions such as behavior, microscopic analyses of tissue organization, and biochemical studies of macromolecules. Genetic and environmental factors that influence these changes are described, and studies that analyze the relationships between different age-related changes are discussed. Together these studies provide fundamental insights into aging in C. elegans that may be relevant to aging in other animals.
{"title":"The measurement and analysis of age-related changes in Caenorhabditis elegans.","authors":"James J Collins, Cheng Huang, Stacie Hughes, Kerry Kornfeld","doi":"10.1895/wormbook.1.137.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.137.1","url":null,"abstract":"<p><p>Aging is characterized by progressive degenerative changes in tissue organization and function that increase the probability of mortality. Major goals of aging research include elucidating the series of events that cause degenerative changes and analyzing environmental and genetic factors that modulate these changes. The basis for mechanistic studies of aging are accurate and precise descriptions of age-related changes, since these descriptions define the aging phenotype. Here we review studies that describe age-related changes in C. elegans including measurements of integrated functions such as behavior, microscopic analyses of tissue organization, and biochemical studies of macromolecules. Genetic and environmental factors that influence these changes are described, and studies that analyze the relationships between different age-related changes are discussed. Together these studies provide fundamental insights into aging in C. elegans that may be relevant to aging in other animals.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2008-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27356216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-11-02DOI: 10.1895/wormbook.1.143.1
Lindy Holden-Dye, Robert J Walker
C. elegans is sensitive to the majority of anthelmintic drugs that are used against parasitic worm infections of humans and livestock. This has provided the opportunity to use molecular genetic techniques in the worm for mode of action studies. These approaches continue to be of considerable value to the field of parasitology. In addition, there are numerous examples of anthelmintic drugs providing exceptionally useful pharmacological tools to delineate fundamental aspects of cell signalling in C. elegans. This has primarily been achieved through the use of anthelmintics in forward genetic screens followed by the mapping and characterization of genes that confer altered susceptibility to the drug. Less fruitful so far, but nonetheless useful, has been the direct use of C. elegans for anthelmintic discovery programmes. In this brief review we provide an introduction to the use of C. elegans as a 'model parasite', outline the actions of the main classes of anthelmintics, and highlight approaches that have been of particular value.
{"title":"Anthelmintic drugs.","authors":"Lindy Holden-Dye, Robert J Walker","doi":"10.1895/wormbook.1.143.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.143.1","url":null,"abstract":"<p><p>C. elegans is sensitive to the majority of anthelmintic drugs that are used against parasitic worm infections of humans and livestock. This has provided the opportunity to use molecular genetic techniques in the worm for mode of action studies. These approaches continue to be of considerable value to the field of parasitology. In addition, there are numerous examples of anthelmintic drugs providing exceptionally useful pharmacological tools to delineate fundamental aspects of cell signalling in C. elegans. This has primarily been achieved through the use of anthelmintics in forward genetic screens followed by the mapping and characterization of genes that confer altered susceptibility to the drug. Less fruitful so far, but nonetheless useful, has been the direct use of C. elegans for anthelmintic discovery programmes. In this brief review we provide an introduction to the use of C. elegans as a 'model parasite', outline the actions of the main classes of anthelmintics, and highlight approaches that have been of particular value.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41019142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-08-08DOI: 10.1895/wormbook.1.144.1
Patrick J Hu
In response to harsh environmental conditions, C. elegans larvae undergo dauer arrest at the second molt. The past decade has yielded many insights into the signaling pathways and the molecular mechanisms that govern this developmental transition. Dauer pheromone, the major physiologic signal promoting dauer arrest, has been purified, identified, and synthesized. The molecular identities of the vast majority of dauer regulatory genes isolated in initial genetic screens are now known. Physiologic ligands for DAF-12, a nuclear receptor that is the final common target of dauer regulatory pathways, have been identified. The discovery of the Hid (high temperature induction of dauer) phenotype and the results of enhancer screens have greatly expanded the repertoire of dauer regulatory genes. Genomic analysis of dauer arrest has highlighted the role of pathway crosstalk in dauer regulation. Nonetheless, critical questions remain about the mechanistic underpinnings of dauer arrest.
{"title":"Dauer.","authors":"Patrick J Hu","doi":"10.1895/wormbook.1.144.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.144.1","url":null,"abstract":"<p><p>In response to harsh environmental conditions, C. elegans larvae undergo dauer arrest at the second molt. The past decade has yielded many insights into the signaling pathways and the molecular mechanisms that govern this developmental transition. Dauer pheromone, the major physiologic signal promoting dauer arrest, has been purified, identified, and synthesized. The molecular identities of the vast majority of dauer regulatory genes isolated in initial genetic screens are now known. Physiologic ligands for DAF-12, a nuclear receptor that is the final common target of dauer regulatory pathways, have been identified. The discovery of the Hid (high temperature induction of dauer) phenotype and the results of enhancer screens have greatly expanded the repertoire of dauer regulatory genes. Genomic analysis of dauer arrest has highlighted the role of pathway crosstalk in dauer regulation. Nonetheless, critical questions remain about the mechanistic underpinnings of dauer arrest.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1895/wormbook.1.144.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41019820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-05-23DOI: 10.1895/wormbook.1.141.1
Mark E Viney, James B Lok
Strongyloides is a genus of parasitic nematodes, which, unusually, has a free-living adult generation. Here we introduce the biology of this genus, especially the fascinating, but complex, life-cycle together with an overview of the taxonomy, morphology, genetics and genomics of this genus.
{"title":"Strongyloides spp.","authors":"Mark E Viney, James B Lok","doi":"10.1895/wormbook.1.141.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.141.1","url":null,"abstract":"<p><p>Strongyloides is a genus of parasitic nematodes, which, unusually, has a free-living adult generation. Here we introduce the biology of this genus, especially the fascinating, but complex, life-cycle together with an overview of the taxonomy, morphology, genetics and genomics of this genus.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41048283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-05-03DOI: 10.1895/wormbook.1.140.1
P G Morgan, E-B Kayser, M M Sedensky
The mechanism of action of volatile anesthetics remains an enigma, despite their worldwide use. The nematode C. elegans has served as an excellent model to unravel this mystery. Genes and gene sets that control the behavior of the animal in volatile anesthetics have been identified, using multiple endpoints to mimic the phenomenon of anesthesia in man. Some of these studies have clear translational implications in more complicated organisms.
{"title":"C. elegans and volatile anesthetics.","authors":"P G Morgan, E-B Kayser, M M Sedensky","doi":"10.1895/wormbook.1.140.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.140.1","url":null,"abstract":"<p><p>The mechanism of action of volatile anesthetics remains an enigma, despite their worldwide use. The nematode C. elegans has served as an excellent model to unravel this mystery. Genes and gene sets that control the behavior of the animal in volatile anesthetics have been identified, using multiple endpoints to mimic the phenomenon of anesthesia in man. Some of these studies have clear translational implications in more complicated organisms.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41048284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-05-03DOI: 10.1895/wormbook.1.139.1
Mingxue Cui, Min Han
It is now well established that cells modify chromatin to establish transcriptionally active or inactive chromosomal regions. Such regulation of the chromatin structure is essential for the proper development of organisms. C. elegans is a powerful organism for exploring the developmental role of chromatin factors and their regulation. This chapter presents an overview of recent studies on chromatin factors in C. elegans with a description of their key roles in a variety of cellular and developmental processes.
{"title":"Roles of chromatin factors in C. elegans development.","authors":"Mingxue Cui, Min Han","doi":"10.1895/wormbook.1.139.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.139.1","url":null,"abstract":"<p><p>It is now well established that cells modify chromatin to establish transcriptionally active or inactive chromosomal regions. Such regulation of the chromatin structure is essential for the proper development of organisms. C. elegans is a powerful organism for exploring the developmental role of chromatin factors and their regulation. This chapter presents an overview of recent studies on chromatin factors in C. elegans with a description of their key roles in a variety of cellular and developmental processes.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41048286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-05-03DOI: 10.1895/wormbook.1.136.1
Bhagwati P Gupta, Robert Johnsen, Nansheng Chen
The soil nematode Caenorhabditis briggsae is an attractive model system for studying evolution of both animal development and behavior. Being a close relative of C. elegans, C. briggsae is frequently used in comparative studies to infer species-specific function of the orthologous genes and also for studying the dynamics of chromosome evolution. The genome sequence of C. briggsae is valuable in reverse genetics and genome-wide comparative studies. This review discusses resources and tools, which are currently available, to facilitate study of C. briggsae in order to unravel mechanisms of gene function that confer morphological and behavioral diversity.
{"title":"Genomics and biology of the nematode Caenorhabditis briggsae.","authors":"Bhagwati P Gupta, Robert Johnsen, Nansheng Chen","doi":"10.1895/wormbook.1.136.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.136.1","url":null,"abstract":"<p><p>The soil nematode Caenorhabditis briggsae is an attractive model system for studying evolution of both animal development and behavior. Being a close relative of C. elegans, C. briggsae is frequently used in comparative studies to infer species-specific function of the orthologous genes and also for studying the dynamics of chromosome evolution. The genome sequence of C. briggsae is valuable in reverse genetics and genome-wide comparative studies. This review discusses resources and tools, which are currently available, to facilitate study of C. briggsae in order to unravel mechanisms of gene function that confer morphological and behavioral diversity.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4781269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41048285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-03-27DOI: 10.1895/wormbook.1.133.1
James D McGhee
The intestine is one of the major organs in C. elegans and is largely responsible for food digestion and assimilation as well as the synthesis and storage of macromolecules. In addition, the intestine is emerging as a powerful experimental system in which to study such universal biological phenomena as vesicular trafficking, biochemical clocks, stress responses and aging. The present chapter describes some of these many and varied properties of the C. elegans intestine: the embryonic cell lineage, intestine morphogenesis, structure and physiology of the intestinal cell and, finally, the transcription factor network controlling intestine development and function.
{"title":"The C. elegans intestine.","authors":"James D McGhee","doi":"10.1895/wormbook.1.133.1","DOIUrl":"https://doi.org/10.1895/wormbook.1.133.1","url":null,"abstract":"<p><p>The intestine is one of the major organs in C. elegans and is largely responsible for food digestion and assimilation as well as the synthesis and storage of macromolecules. In addition, the intestine is emerging as a powerful experimental system in which to study such universal biological phenomena as vesicular trafficking, biochemical clocks, stress responses and aging. The present chapter describes some of these many and varied properties of the C. elegans intestine: the embryonic cell lineage, intestine morphogenesis, structure and physiology of the intestinal cell and, finally, the transcription factor network controlling intestine development and function.</p>","PeriodicalId":75344,"journal":{"name":"WormBook : the online review of C. elegans biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41048287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}