The FEBS journal最新文献

{"title":"A guide to RNA structure analysis and RNA-targeting methods.","authors":"Rodrigo Aguilar, Constanza Mardones, Adrian A Moreno, Marjorie Cepeda-Plaza","doi":"10.1111/febs.17368","DOIUrl":"https://doi.org/10.1111/febs.17368","url":null,"abstract":"<p><p>RNAs are increasingly recognized as promising therapeutic targets, susceptible to modulation by strategies that include targeting with small molecules, antisense oligonucleotides, deoxyribozymes (DNAzymes), or CRISPR/Cas13. However, while drug development for proteins follows well-established paths for rational design based on the accurate knowledge of their three-dimensional structure, RNA-targeting strategies are challenging since comprehensive RNA structures are yet scarce and challenging to acquire. Numerous methods have been developed to elucidate the secondary and three-dimensional structure of RNAs, including X-ray crystallography, cryo-electron microscopy, nuclear magnetic resonance, SHAPE, DMS, and bioinformatic methods, yet they have often revealed flexible transcripts and co-existing populations rather than single-defined structures. Thus, researchers aiming to target RNAs face a critical decision: whether to acquire the detailed structure of transcripts in advance or to adopt phenotypic screens or sequence-based approaches that are independent of the structure. Still, even in strategies that seem to rely only on the nucleotide sequence (like the design of antisense oligonucleotides), researchers may need information about the accessibility of the compounds to the folded RNA molecule. In this concise guide, we provide an overview for researchers interested in targeting RNAs: We start by revisiting current methodologies for defining secondary or three-dimensional RNA structure and then we explore RNA-targeting strategies that may or may not require an in-depth knowledge of RNA structure. We envision that complementary approaches may expedite the development of RNA-targeting molecules to combat disease.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883872","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":"SignatureFinder enables sequence mining to identify cobalamin-dependent photoreceptor proteins.","authors":"Yuqi Yu, Laura N Jeffreys, Harshwardhan Poddar, Adam Hill, Linus Johannissen, Fanzhuo Dai, Michiyo Sakuma, David Leys, Derren J Heyes, Shaowei Zhang, Nigel S Scrutton","doi":"10.1111/febs.17377","DOIUrl":"https://doi.org/10.1111/febs.17377","url":null,"abstract":"<p><p>Photoreceptors control cellular processes in response to light. Most photoreceptors sense blue or red light, but the recent discovery of the cobalamin-dependent photoreceptor, CarH, has expanded the wavelength range of photoreception to other regions of the electromagnetic spectrum to include the green light region. Further identification of cobalamin-dependent green light-sensitive photoreceptors has been hampered owing to poor annotation of the light responsiveness of cobalamin-binding domains (CBDs) in public databases. Here we report a computational workflow, SignatureFinder, that uses a combination of sequence and structural analyses to identify new light-responsive CBD-containing proteins. The light response of exemplar proteins containing the proposed signature were confirmed experimentally. A structural analysis of these new photoreceptors, including the crystal structure of a new CBD domain, highlights how the signature elements interact with the cobalamin chromophore to sense light. Database mining of 128 000 CBD-containing sequences using the identified signature revealed more diverse CBD-containing photoreceptors, thereby expanding the family of green-light photoreceptors. A SignatureFinder web server is available (https://enzymeevolver.com) for wider applications, including the identification of signature sequences of other biological ligands of interest.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883882","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":"The gut microbiota mediates memory impairment under high-altitude hypoxia via the gut-brain axis in mice.","authors":"Wenhao Li, Yuhao Wang, Yi Shi, Fenfen He, Zaihua Zhao, Jingchun Liu, Zhenbo Gao, Jianbin Zhang, Xuefeng Shen","doi":"10.1111/febs.17365","DOIUrl":"https://doi.org/10.1111/febs.17365","url":null,"abstract":"<p><p>Hypoxia is a predominant risk factor at high altitudes, and evidence suggests that high-altitude hypoxia alters the gut microbiota, which plays an essential regulatory role in memory function. However, the causal relationship between the gut microbiota and memory impairment under hypoxic conditions remains unclear. In this study, we employed a high-altitude hypoxia model combined with fecal microbiota transplantation (FMT) approach in mice to explore the effects of the gut microbiota on memory impairment in a hypoxic environment. We observed that high-altitude hypoxia exposure reduced short- and long-term memory and hippocampus-dependent fear memory abilities, along with decreased relative abundance of Ligilactobacillus and Muribaculum. Moreover, hypoxic conditions increased intestinal and blood-brain barrier permeability. FMT from hypoxia-exposed mice into naïve antibiotic-treated mice resulted in similar memory impairments, Ligilactobacillus and Muribaculum abundance changes, and increased intestinal/blood-brain barrier permeability. Correlation analysis showed a robust positive association between Ligilactobacillus and Muribaculum with hippocampus-dependent contextual fear memory. Likewise, Ligilactobacillus was positively correlated with short-term memory. Therefore, Ligilactobacillus and Muribaculum may be key microbes in reducing memory ability in hypoxia, with the intestinal and blood-brain barriers as primary pathways. Our findings provide further evidence for the potential regulatory mechanism by which gut microbiota dysbiosis may contribute to memory impairment in a high-altitude environment.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883887","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":"Transglutaminase 2 is an RNA-binding protein: experimental verification and characterisation of a novel transglutaminase feature.","authors":"Bianka Csaholczi, Anna Renáta Csuth, Ilma Rita Korponay-Szabó, László Fésüs, Róbert Király","doi":"10.1111/febs.17373","DOIUrl":"https://doi.org/10.1111/febs.17373","url":null,"abstract":"<p><p>Transglutaminase 2 (TG2) is a uniquely versatile protein with diverse catalytic activities, such as transglutaminase, protein disulfide isomerase, GTPase and protein kinase, and participates in several biological processes. According to information available in the RBP2GO database, TG2 can act as an RNA-binding protein (RBP). RBPs participate in posttranscriptional gene expression regulation, therefore influencing the function of RNA, whereas RNA molecules can also modulate the biological activity of RBPs. The present study aimed to confirm this novel characteristic of TG2 in human umbilical cord vein endothelial cells (HUVEC), which physiologically express TG2. First, UV cross-linked RNA-protein complexes were isolated from immortalised HUVECs using orthogonal organic phase separation. Compared with the RBP2GO database, mass spectrometry identified 392 potential RBPs, including TG2 and 20 previously undescribed, endothelium-related RBPs. Recombinant human TG2 was also pulled down by magnetic bead-immobilised total RNA from HUVEC. Complex formation between TG2 and a 43-mer RNA molecule with a secondary structure as well as a homo-oligomeric single-stranded poly(dG), but not poly(dA), could be observed in magnetic RNA-protein pull-down experiments. Experiments with TG2 inhibitors NC9 and GTPγS, which stabilise its open and closed conformation, respectively, revealed that the open conformation of the enzyme favoured RNA-binding. Biolayer interferometry revealed a high binding affinity between TG2 and RNA with a K_D value of 88 nm. Based on modelling and site-directed mutagenesis studies, we propose that superficial residues on the catalytic core domain (173-177 amino acids), present in a hidden position in the closed TG2 conformation, are involved in RNA binding. The present study demonstrates the previously uncharacterised RNA-binding ability of TG2, opening new avenues for understanding its multifunctionality.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883893","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":"Hypoxia-induced translation of collagen-modifying enzymes PLOD2 and P4HA1 is dependent on RBM4 and eIF4E2 in human colon cancer HCT116 cells.","authors":"Hung-Hsuan Li, Hsin-Yuan Hung, Jau-Song Yu, Yu-Cheng Liao, Ming-Chih Lai","doi":"10.1111/febs.17371","DOIUrl":"https://doi.org/10.1111/febs.17371","url":null,"abstract":"<p><p>Hypoxia is a critical microenvironmental factor that induces tumorigenesis and cancer progression, including metastasis. The highly dynamic nature of the extracellular matrix (ECM) plays a crucial role in metastasis. Collagens are the predominant component of structural proteins embedded within the ECM. The biosynthesis of collagen typically undergoes a series of posttranslational modifications, such as hydroxylation of lysine and proline residues by procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) and prolyl 4-hydroxylases (P4Hs), respectively. Collagen hydroxylation is critical for ECM remodeling and maintenance. We recently investigated hypoxia-induced translation in human colon cancer HCT116 cells and identified several collagen-modifying enzymes, including procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) and prolyl 4-hydroxylase subunit alpha 1 (P4HA1). Although the translation of bulk mRNAs is repressed in hypoxia, specific mRNAs remain efficiently translated under such conditions. We have found that PLOD2 and P4HA1 are significantly upregulated in hypoxic HCT116 cells compared to normoxic cells. HIF-1 is known to induce the transcription of PLOD2 and P4HA1 during hypoxia. However, the molecular mechanisms of hypoxia-induced translation of PLOD2 and P4HA1 remain largely unclear. We provide evidence that RBM4 and eIF4E2 are required for hypoxia-induced translation of PLOD2 and P4HA1 mRNAs. The 3' UTRs of PLOD2 and P4HA1 mRNAs are involved in translational control during hypoxia in HCT116 cells.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879237","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":"Integrated proteomics and connectivity map-based analysis reveal compounds with a potential antiviral effect against Japanese encephalitis virus infection in a mouse model.","authors":"Rohit Soni, Naina Soni, Abhijit Paul, Aarti Tripathi, Samrat Chatterjee, Arup Banerjee","doi":"10.1111/febs.17370","DOIUrl":"https://doi.org/10.1111/febs.17370","url":null,"abstract":"<p><p>Japanese encephalitis virus (JEV) is the leading causative agent of viral encephalitis in India and contributes to a significant disease burden in South Asian countries. However, no antiviral treatment is available against JEV-induced encephalitis, highlighting the urgent need for novel therapeutic approaches. Repurposing or repositioning drugs was found to be more economical and practical in the current drug development scenario. The present study aimed to develop a host-directed strategy through a computational drug repurposing approach. As part of the strategy, we first generated a dynamic signature of differentially expressed JEV infection-associated proteins in mice brains through a semiquantitative proteomics approach. With the help of the Connectivity Map (CMap) analysis, we narrowed down the lists of drugs with a high negative CMap score (-70 or lower). Based on the CMap score, we chose the top three compounds (Tipifarnib, Ly303511 and MDL11939) with CMap scores of -91.83, -88.18 and -91.15, respectively. The antiviral potential of these three compounds was further compared in both JEV-infected mouse neuroblastoma cells and C57BL/6 mice. Oral administration of Ly303511 and MDL11939, alone or in combination, showed improved outcomes (e.g. delayed death, increased survival, and less viral load than Tipifarnib alone or combined). The JEV-infected mice survived upon drug treatment, effectively reducing viral load and reversing the antiviral signature. Our results highlight Ly303511 and MDL11939 as promising host-targeted inhibitors of JEV infection and pathogenesis. Moreover, our results favor the combination of Ly303511 and MDL11939 therapy to improve clinical symptoms and reduce JEV-induced damage, thus warranting inclusion in clinical studies.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879240","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":"Evidence for corrin biosynthesis in the last universal common ancestor.","authors":"Luca D Modjewski, Val Karavaeva, Natalia Mrnjavac, Michael Knopp, William F Martin, Filipa L Sousa","doi":"10.1111/febs.17367","DOIUrl":"https://doi.org/10.1111/febs.17367","url":null,"abstract":"<p><p>Corrinoids are cobalt-containing tetrapyrroles. They include adenosylcobalamin (vitamin B₁₂) and cobamides that function as cofactors and coenzymes for methyl transfer, radical-dependent and redox reactions. Though cobamides are the most complex cofactors in nature, they are essential in the acetyl-CoA pathway, thought to be the most ancient CO₂-fixation pathway, where they perform a pterin-to-cobalt-to-nickel methyl transfer reaction catalyzed by the corrinoid iron-sulphur protein (CoFeS). CoFeS occurs in H₂-dependent archaeal methanogens, the oldest microbial lineage by measure of physiology and carbon isotope data, dating corrinoids to ca. 3.5 billion years. However, CoFeS and cobamides are also essential in the acetyl-CoA pathway of H₂-dependent bacterial acetogens. To determine whether corrin biosynthesis was established before archaea and bacteria diverged, whether the pathways arose independently or whether cobamide biosynthesis was transferred from the archaeal to the bacterial lineage (or vice versa) during evolution, we investigated phylogenies and structural data for 26 enzymes of corrin ring and lower ligand biosynthesis. The data trace cobamide synthesis to the common ancestor of bacteria and archaea, placing it in the last universal common ancestor of all lifeforms (LUCA), while pterin-dependent methyl synthesis pathways likely arose independently post-LUCA in the lineages leading to bacteria and archaea. Enzymes of corrin biosynthesis were recruited from preexisting ancient pathways. Evolutionary forerunners of CoFeS function were likely Fe-, Ni- and Co-containing solid-state surfaces, which, in the laboratory, catalyze the reactions of the acetyl-CoA pathway from CO₂ to pyruvate under serpentinizing hydrothermal conditions. The data suggest that enzymatic corrin biosynthesis replaced insoluble solid-state catalysts that tethered primordial CO₂ assimilation to the Earth's crust, suggesting a role for corrin synthesis in the origin of free-living cells.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873660","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":"Bacterial purine metabolism modulates C. elegans development and stress tolerance via DAF-16.","authors":"Min Feng, Baizhen Gao, L Rene Garcia, Qing Sun","doi":"10.1111/febs.17363","DOIUrl":"https://doi.org/10.1111/febs.17363","url":null,"abstract":"<p><p>The purine metabolism is crucial for cellular function and is a conserved metabolic network from prokaryotes to humans. While extensively studied in microorganisms like yeast and bacteria, the impact of perturbing dietary intermediates from the purine biosynthesis on animal development and growth remains poorly understood. We utilized Caenorhabditis elegans as the metazoan model to investigate the mechanisms underlying this deficiency. Through a high-throughput screening of an Escherichia coli mutant library Keio collection, we identified 34 E. coli mutants that delay C. elegans development. Among these mutants, we found that E. coli purE gene is an essential genetic component that promotes host development in a dose-dependent manner. Further metabolites supplementation suggests that bacterial purE downstream metabolite 5-aminoimidazole-4-carboxamide ribotide (AICAR) can inhibit worm growth. Additionally, we found the FoxO transcription factor DAF-16 is indispensable in worm development delay induced by purE mutation, and observed increased nuclear accumulation of DAF-16 when fed E. coli purE- mutants, suggesting the role of DAF-16 in response to purE mutation. RNA-seq analysis and phenotypic assays revealed that worms fed the E. coli purE mutant exhibited elevated lifespan, thermotolerance, and pathogen resistance. These findings collectively suggest that certain intermediates in the bacterial purine biosynthesis can serve as a cue to modulate development and activate the defense response in the nematode C. elegans through DAF-16.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873684","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":"Transcriptional factor ISL1 regulates palate development by tuning the SHH cascade.","authors":"Chujing Zhang, Yuting Zheng, Yaping Qu, Ruiqi Huang, Huarong Huang, Jianying Li, Mengsheng Qiu, Feixue Li","doi":"10.1111/febs.17369","DOIUrl":"https://doi.org/10.1111/febs.17369","url":null,"abstract":"<p><p>Cleft palate is one of the most common birth defects in humans, and palate morphogenesis depends on epithelial-mesenchymal interaction. In this study, we report that ablation of Isl1 in the epithelium leads to complete cleft palate. A significant reduction in mesenchymal cell proliferation was detected in the Isl1^Pitx2Cre mutant palates, but there was no significant difference in apoptosis between wild-type and mutant embryos. Fewer rugae structures were observed in Isl1^Pitx2Cre mutant embryos. Shh, Sox2, Foxe1, Foxd2, and Msx1 expression was downregulated in the developing palate in Isl1 mutant embryos. We found that ISL1 can directly regulate Shh expression in palatal epithelial cells, suggesting a critical role for ISL1 in epithelial-mesenchymal interactions during palate development. Remarkably, cleft palate defects due to Isl1 deletion were rescued by a conditional transgenic allele (Tg-pmes-Ihh), confirming the genetic integration of Hedgehog signaling. Our findings indicate that ISL1 controls palatal shelf morphogenesis by modulating epithelial-mesenchymal communication via SHH signaling.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866923","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":"Conversion of pyridoxal to pyridoxamine with NH₃ and H₂ on nickel generates a protometabolic nitrogen shuttle under serpentinizing conditions.","authors":"Manon Laura Schlikker, Max Brabender, Loraine Schwander, Carolina Garcia Garcia, Maximillian Burmeister, Sabine Metzger, Joseph Moran, William F Martin","doi":"10.1111/febs.17357","DOIUrl":"https://doi.org/10.1111/febs.17357","url":null,"abstract":"<p><p>Serpentinizing hydrothermal vents are likely sites for the origin of metabolism because they produce H₂ as a source of electrons for CO₂ reduction while depositing zero-valent iron, cobalt, and nickel as catalysts for organic reactions. Recent work has shown that solid-state nickel can catalyze the H₂-dependent reduction of CO₂ to various organic acids and their reductive amination with H₂ and NH₃ to biological amino acids under the conditions of H₂-producing hydrothermal vents and that amino acid synthesis from NH₃, H₂, and 2-oxoacids is facile in the presence of Ni⁰. Such reactions suggest a metallic origin of metabolism during early biochemical evolution because single metals replace the function of over 130 enzymatic reactions at the core of metabolism in microbes that use the acetyl-CoA pathway of CO₂ fixation. Yet solid-state catalysts tether primordial amino synthesis to a mineral surface. Many studies have shown that pyridoxal catalyzes transamination reactions without enzymes. Here we show that pyridoxamine, the NH₂-transferring intermediate in pyridoxal-dependent transamination reactions, is generated from pyridoxal by reaction with NH₃ (as little as 5 mm) and H₂ (5 bar) on Ni⁰ as catalyst at pH 11 and 80 °C within hours. These conditions correspond to those in hydrothermal vents undergoing active serpentinization. The results indicate that at the origin of metabolism, pyridoxamine provided a soluble, organic amino donor for aqueous amino acid synthesis, mediating an evolutionary transition from NH₃-dependent amino acid synthesis on inorganic surfaces to pyridoxamine-dependent organic reactions in the aqueous phase.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866907","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}