{"title":"Pathogen vacuole membrane contact sites - close encounters of the fifth kind.","authors":"Simone Vormittag, Rachel J Ende, Isabelle Derré, Hubert Hilbi","doi":"10.1093/femsml/uqad018","DOIUrl":"https://doi.org/10.1093/femsml/uqad018","url":null,"abstract":"<p><p>Vesicular trafficking and membrane fusion are well-characterized, versatile, and sophisticated means of 'long range' intracellular protein and lipid delivery. Membrane contact sites (MCS) have been studied in far less detail, but are crucial for 'short range' (10-30 nm) communication between organelles, as well as between pathogen vacuoles and organelles. MCS are specialized in the non-vesicular trafficking of small molecules such as calcium and lipids. Pivotal MCS components important for lipid transfer are the VAP receptor/tether protein, oxysterol binding proteins (OSBPs), the ceramide transport protein CERT, the phosphoinositide phosphatase Sac1, and the lipid phosphatidylinositol 4-phosphate (PtdIns(4)<i>P</i>). In this review, we discuss how these MCS components are subverted by bacterial pathogens and their secreted effector proteins to promote intracellular survival and replication.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad018"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522023","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}
microLifePub Date : 2023-01-01DOI: 10.1093/femsml/uqad014
Vanessa Kreiling, Kai M Thormann
{"title":"Polarity of c-di-GMP synthesis and degradation.","authors":"Vanessa Kreiling, Kai M Thormann","doi":"10.1093/femsml/uqad014","DOIUrl":"https://doi.org/10.1093/femsml/uqad014","url":null,"abstract":"<p><p>The bacterial cell pole has long been recognized as a defined compartment for enzymatic activities that are important or even vital for the cell. Polarity of diguanylate cyclases and phosphodiesterases, enzymes that synthesize and degrade the second messenger c-di-GMP, has now been demonstrated for several bacterial systems. Here we review these polar regulatory systems and show how the asymmetry of c-di-GMP production and turnover in concert with different modes of activation and deactivation creates heterogeneity in cellular c-di-GMP levels. We highlight how this heterogeneity generates a diverse set of phenotypic identities or states and how this may benefit the cell population, and we discuss reasons why the polarity of c-di-GMP signaling is probably widespread among bacteria.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad014"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545271","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}
microLifePub Date : 2023-01-01DOI: 10.1093/femsml/uqad023
Sarah Wettstadt
{"title":"Unravelling evolution one nucleotide at a time.","authors":"Sarah Wettstadt","doi":"10.1093/femsml/uqad023","DOIUrl":"https://doi.org/10.1093/femsml/uqad023","url":null,"abstract":"Throughout her journey of becoming a microbiology researcher, Siv Andersson would change course every four or five years. ‘I usually just turn around, see what’s available and run off into the direction that looks most exciting, interesting, and challenging’. Every few years, important life decisions impacted her career and somehow paved her journey into academic research. After postdocs at the Laboratory of Molecular Biology in Cambridge and Columbia Medical School in New York, she became an Associate Professor at Uppsala University in 1997, where she had finished her Ph.D. Dissertation. In 2000, she became full Professor for Molecular Evolution and was Head of the Department of Evolution, Genomics, and Systematics at the Evolutionary Biology Centre from 2003 to 2009. Now being more open for long-term goals, Siv investigates how bacteria evolved throughout time; she even looked at time ranges of several million years. Siv and her group explored how two lineages of the bacterium Buchnera aphidicola adapted to their specific hosts, the pea aphid and the wheat aphid (Tamas et al. 2002). This endosymbiosis was established ∼150 million years ago, and the two lineages diverged ∼50–70 million years ago. Interestingly— and completely unexpectedly—they found that even though both lineages were living as endosymbionts with their respective hosts for such a long time, their gene contents barely differ. ‘When we looked at the gene maps and saw they were identical; we were just silent. And then the Ph.D. student started panicking because he thought the samples had been mixed up and the same bacterium had been sequenced twice.’ Later, they found that indeed a high degree of divergence was apparent at the nucleotide sequence level. Yet, no inversions, translocations, duplications, or gene acquisitions seemed to have happened throughout this extensive time period. With both endosymbionts having lost the genetic elements for a recombination machinery, their genome size and flexibility were reduced, which instead increased genome stability and left them with the same genomic architecture. As the next step, Siv aimed to understand the mechanisms of how B. aphidicola adapted to its aphid host (Tamas et al. 2008). This endosymbiont has one of the smallest and most A-T-rich bacterial genomes and some of its transcripts with poly(A) sequences contain frameshift mutations resulting in nonfunctional gene products. Yet, as Siv and her group found, transcriptional slippage of the polymerase can rescue these mutations and—against the odds—lead to functional gene products. Even though a seemingly inefficient mode of information processing, regulation mechanisms like these could be helpful in designing synthetic genomes.","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad023"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/bf/uqad023.PMC10132846.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522020","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}
microLifePub Date : 2023-01-01DOI: 10.1093/femsml/uqad017
Kristina Driller, Fabián A Cornejo, Kürşad Turgay
{"title":"(p)ppGpp - an important player during heat shock response.","authors":"Kristina Driller, Fabián A Cornejo, Kürşad Turgay","doi":"10.1093/femsml/uqad017","DOIUrl":"https://doi.org/10.1093/femsml/uqad017","url":null,"abstract":"<p><p>The alarmones and second messengers (p)ppGpp are important for the cellular response to amino acid starvation. Although the stringent response is present in many bacteria, the targets and functions of (p)ppGpp can differ between species, and our knowledge of (p)ppGpp targets is constantly expanding. Recently, it was demonstrated that these alarmones are also part of the heat shock response in <i>Bacillus subtilis</i> and that there is a functional overlap with the oxidative and heat stress transcriptional regulator Spx. Here, the (p)ppGpp second messenger alarmones allow the fast stress-induced downregulation of translation while Spx inhibits the further expression of translation-related genes to lower the load on the protein quality control system, while the chaperone and protease expression is induced. In this review, we discuss the role of (p)ppGpp and its intricate connections in the complex network of stress sensing, heat shock response, and adaptation in <i>B. subtilis</i> cells.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad017"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10212131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545269","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}
microLifePub Date : 2023-01-01DOI: 10.1093/femsml/uqad024
Elizaveta Krol, Laura Werel, Lars Oliver Essen, Anke Becker
{"title":"Structural and functional diversity of bacterial cyclic nucleotide perception by CRP proteins.","authors":"Elizaveta Krol, Laura Werel, Lars Oliver Essen, Anke Becker","doi":"10.1093/femsml/uqad024","DOIUrl":"https://doi.org/10.1093/femsml/uqad024","url":null,"abstract":"<p><p>Cyclic AMP (cAMP) is a ubiquitous second messenger synthesized by most living organisms. In bacteria, it plays highly diverse roles in metabolism, host colonization, motility, and many other processes important for optimal fitness. The main route of cAMP perception is through transcription factors from the diverse and versatile CRP-FNR protein superfamily. Since the discovery of the very first CRP protein CAP in <i>Escherichia coli</i> more than four decades ago, its homologs have been characterized in both closely related and distant bacterial species. The cAMP-mediated gene activation for carbon catabolism by a CRP protein in the absence of glucose seems to be restricted to <i>E. coli</i> and its close relatives. In other phyla, the regulatory targets are more diverse. In addition to cAMP, cGMP has recently been identified as a ligand of certain CRP proteins. In a CRP dimer, each of the two cyclic nucleotide molecules makes contacts with both protein subunits and effectuates a conformational change that favors DNA binding. Here, we summarize the current knowledge on structural and physiological aspects of <i>E. coli</i> CAP compared with other cAMP- and cGMP-activated transcription factors, and point to emerging trends in metabolic regulation related to lysine modification and membrane association of CRP proteins.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqad024"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/d8/uqad024.PMC10187061.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9570011","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}
microLifePub Date : 2022-12-27eCollection Date: 2023-01-01DOI: 10.1093/femsml/uqac027
Charlotte Michaux, Milan Gerovac, Elisabeth E Hansen, Lars Barquist, Jörg Vogel
{"title":"Grad-seq analysis of <i>Enterococcus faecalis</i> and <i>Enterococcus faecium</i> provides a global view of RNA and protein complexes in these two opportunistic pathogens.","authors":"Charlotte Michaux, Milan Gerovac, Elisabeth E Hansen, Lars Barquist, Jörg Vogel","doi":"10.1093/femsml/uqac027","DOIUrl":"10.1093/femsml/uqac027","url":null,"abstract":"<p><p><i>Enterococcus faecalis</i> and <i>Enterococcus faecium</i> are major nosocomial pathogens. Despite their relevance to public health and their role in the development of bacterial antibiotic resistance, relatively little is known about gene regulation in these species. RNA-protein complexes serve crucial functions in all cellular processes associated with gene expression, including post-transcriptional control mediated by small regulatory RNAs (sRNAs). Here, we present a new resource for the study of enterococcal RNA biology, employing the Grad-seq technique to comprehensively predict complexes formed by RNA and proteins in <i>E. faecalis</i> V583 and <i>E. faecium</i> AUS0004. Analysis of the generated global RNA and protein sedimentation profiles led to the identification of RNA-protein complexes and putative novel sRNAs. Validating our data sets, we observe well-established cellular RNA-protein complexes such as the 6S RNA-RNA polymerase complex, suggesting that 6S RNA-mediated global control of transcription is conserved in enterococci. Focusing on the largely uncharacterized RNA-binding protein KhpB, we use the RIP-seq technique to predict that KhpB interacts with sRNAs, tRNAs, and untranslated regions of mRNAs, and might be involved in the processing of specific tRNAs. Collectively, these datasets provide departure points for in-depth studies of the cellular interactome of enterococci that should facilitate functional discovery in these and related Gram-positive species. Our data are available to the community through a user-friendly Grad-seq browser that allows interactive searches of the sedimentation profiles (https://resources.helmholtz-hiri.de/gradseqef/).</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqac027"},"PeriodicalIF":0.0,"publicationDate":"2022-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516279","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}
microLifePub Date : 2022-12-20eCollection Date: 2023-01-01DOI: 10.1093/femsml/uqac025
Eduard Fadeev, Cécile Carpaneto Bastos, Jennifer H Hennenfeind, Steven J Biller, Daniel Sher, Matthias Wietz, Gerhard J Herndl
{"title":"Characterization of membrane vesicles in <i>Alteromonas macleodii</i> indicates potential roles in their copiotrophic lifestyle.","authors":"Eduard Fadeev, Cécile Carpaneto Bastos, Jennifer H Hennenfeind, Steven J Biller, Daniel Sher, Matthias Wietz, Gerhard J Herndl","doi":"10.1093/femsml/uqac025","DOIUrl":"10.1093/femsml/uqac025","url":null,"abstract":"<p><p>Bacterial membrane vesicles (MVs) are abundant in the oceans, but their potential functional roles remain unclear. In this study we characterized MV production and protein content of six strains of <i>Alteromonas macleodii</i>, a cosmopolitan marine bacterium. <i>Alteromonas macleodii</i> strains varied in their MV production rates, with some releasing up to 30 MVs per cell per generation. Microscopy imaging revealed heterogenous MV morphologies, including some MVs aggregated within larger membrane structures. Proteomic characterization revealed that <i>A. macleodii</i> MVs are rich in membrane proteins related to iron and phosphate uptake, as well as proteins with potential functions in biofilm formation. Furthermore, MVs harbored ectoenzymes, such as aminopeptidases and alkaline phosphatases, which comprised up to 20% of the total extracellular enzymatic activity. Our results suggest that <i>A. macleodii</i> MVs may support its growth through generation of extracellular 'hotspots' that facilitate access to essential substrates. This study provides an important basis to decipher the ecological relevance of MVs in heterotrophic marine bacteria.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"4 ","pages":"uqac025"},"PeriodicalIF":0.0,"publicationDate":"2022-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/5a/uqac025.PMC10117737.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516277","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}
microLifePub Date : 2022-11-02eCollection Date: 2022-01-01DOI: 10.1093/femsml/uqac022
Maxime Ardré, Guilhem Doulcier, Naama Brenner, Paul B Rainey
{"title":"A leader cell triggers end of lag phase in populations of <i>Pseudomonas fluorescens</i>.","authors":"Maxime Ardré, Guilhem Doulcier, Naama Brenner, Paul B Rainey","doi":"10.1093/femsml/uqac022","DOIUrl":"10.1093/femsml/uqac022","url":null,"abstract":"Abstract The relationship between the number of cells colonizing a new environment and time for resumption of growth is a subject of long-standing interest. In microbiology this is known as the “inoculum effect.” Its mechanistic basis is unclear with possible explanations ranging from the independent actions of individual cells, to collective actions of populations of cells. Here, we use a millifluidic droplet device in which the growth dynamics of hundreds of populations founded by controlled numbers of Pseudomonas fluorescens cells, ranging from a single cell, to one thousand cells, were followed in real time. Our data show that lag phase decreases with inoculum size. The decrease of average lag time and its variance across droplets, as well as lag time distribution shapes, follow predictions of extreme value theory, where the inoculum lag time is determined by the minimum value sampled from the single-cell distribution. Our experimental results show that exit from lag phase depends on strong interactions among cells, consistent with a “leader cell” triggering end of lag phase for the entire population.","PeriodicalId":74189,"journal":{"name":"microLife","volume":"3 ","pages":"uqac022"},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516244","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}
microLifePub Date : 2022-08-10eCollection Date: 2022-01-01DOI: 10.1093/femsml/uqac014
Monica Rolando, Cristina Di Silvestre, Laura Gomez-Valero, Carmen Buchrieser
{"title":"Bacterial methyltransferases: from targeting bacterial genomes to host epigenetics.","authors":"Monica Rolando, Cristina Di Silvestre, Laura Gomez-Valero, Carmen Buchrieser","doi":"10.1093/femsml/uqac014","DOIUrl":"10.1093/femsml/uqac014","url":null,"abstract":"<p><p>Methyltransferase (MTases) enzymes transfer methyl groups particularly on proteins and nucleotides, thereby participating in controlling the epigenetic information in both prokaryotes and eukaryotes. The concept of epigenetic regulation by DNA methylation has been extensively described for eukaryotes. However, recent studies have extended this concept to bacteria showing that DNA methylation can also exert epigenetic control on bacterial phenotypes. Indeed, the addition of epigenetic information to nucleotide sequences confers adaptive traits including virulence-related characteristics to bacterial cells. In eukaryotes, an additional layer of epigenetic regulation is obtained by post-translational modifications of histone proteins. Interestingly, in the last decades it was shown that bacterial MTases, besides playing an important role in epigenetic regulations at the microbe level by exerting an epigenetic control on their own gene expression, are also important players in host-microbe interactions. Indeed, secreted nucleomodulins, bacterial effectors that target the nucleus of infected cells, have been shown to directly modify the epigenetic landscape of the host. A subclass of nucleomodulins encodes MTase activities, targeting both host DNA and histone proteins, leading to important transcriptional changes in the host cell. In this review, we will focus on lysine and arginine MTases of bacteria and their hosts. The identification and characterization of these enzymes will help to fight bacterial pathogens as they may emerge as promising targets for the development of novel epigenetic inhibitors in both bacteria and the host cells they infect.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"3 ","pages":"uqac014"},"PeriodicalIF":0.0,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9888094","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}
microLifePub Date : 2022-05-18eCollection Date: 2022-01-01DOI: 10.1093/femsml/uqac006
Andrea Qvortrup Holst, Harshitha Jois, Martin Frederik Laursen, Morten O A Sommer, Tine Rask Licht, Martin Iain Bahl
{"title":"Human milk oligosaccharides induce acute yet reversible compositional changes in the gut microbiota of conventional mice linked to a reduction of butyrate levels.","authors":"Andrea Qvortrup Holst, Harshitha Jois, Martin Frederik Laursen, Morten O A Sommer, Tine Rask Licht, Martin Iain Bahl","doi":"10.1093/femsml/uqac006","DOIUrl":"10.1093/femsml/uqac006","url":null,"abstract":"<p><p>Human Milk Oligosaccharides (HMOs) are glycans with prebiotic properties known to drive microbial selection in the infant gut, which in turn influences immune development and future health. Bifidobacteria are specialized in HMO degradation and frequently dominate the gut microbiota of breastfed infants. However, some species of <i>Bacteroidaceae</i> also degrade HMOs, which may prompt selection also of these species in the gut microbiota. To investigate to what extent specific HMOs affect the abundance of naturally occurring <i>Bacteroidaceae</i> species in a complex mammalian gut environment, we conducted a study in 40 female NMRI mice administered three structurally different HMOs, namely 6'sialyllactose (6'SL, <i>n</i> = 8), 3-fucosyllactose (3FL, <i>n</i> = 16), and Lacto-N-Tetraose (LNT, <i>n</i> = 8), through drinking water (5%). Compared to a control group receiving unsupplemented drinking water (<i>n</i> = 8), supplementation with each of the HMOs significantly increased both the absolute and relative abundance of <i>Bacteroidaceae</i> species in faecal samples and affected the overall microbial composition analyzed by 16s rRNA amplicon sequencing. The compositional differences were mainly attributed to an increase in the relative abundance of the genus <i>Phocaeicola</i> (formerly <i>Bacteroides</i>) and a concomitant decrease of the genus <i>Lacrimispora</i> (formerly <i>Clostridium</i> XIVa cluster). During a 1-week washout period performed specifically for the 3FL group, this effect was reversed. Short-chain fatty acid analysis of faecal water revealed a decrease in acetate, butyrate and isobutyrate levels in animals supplemented with 3FL, which may reflect the observed decrease in the <i>Lacrimispora</i> genus. This study highlights HMO-driven <i>Bacteroidaceae</i> selection in the gut environment, which may cause a reduction of butyrate-producing clostridia.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"3 ","pages":"uqac006"},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516240","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}