microLife最新文献

{"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}

{"title":"(p)ppGpp - an important player during heat shock response.","authors":"Kristina Driller,&nbsp;Fabián A Cornejo,&nbsp;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}

{"title":"Structural and functional diversity of bacterial cyclic nucleotide perception by CRP proteins.","authors":"Elizaveta Krol,&nbsp;Laura Werel,&nbsp;Lars Oliver Essen,&nbsp;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}

{"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}

{"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}

{"title":"A leader cell triggers end of lag phase in populations of <i>Pseudomonas fluorescens</i>.","authors":"Maxime Ardré,&nbsp;Guilhem Doulcier,&nbsp;Naama Brenner,&nbsp;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}

{"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}

{"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}

{"title":"Hidden in plain sight: challenges in proteomics detection of small ORF-encoded polypeptides.","authors":"Igor Fijalkowski, Patrick Willems, Veronique Jonckheere, Laure Simoens, Petra Van Damme","doi":"10.1093/femsml/uqac005","DOIUrl":"10.1093/femsml/uqac005","url":null,"abstract":"<p><p>Genomic studies of bacteria have long pointed toward widespread prevalence of small open reading frames (sORFs) encoding for short proteins, <100 amino acids in length. Despite the mounting genomic evidence of their robust expression, relatively little progress has been made in their mass spectrometry-based detection and various blanket statements have been used to explain this observed discrepancy. In this study, we provide a large-scale riboproteogenomics investigation of the challenging nature of proteomic detection of such small proteins as informed by conditional translation data. A panel of physiochemical properties alongside recently developed mass spectrometry detectability metrics was interrogated to provide a comprehensive evidence-based assessment of sORF-encoded polypeptide (SEP) detectability. Moreover, a large-scale proteomics and translatomics compendium of proteins produced by <i>Salmonella</i> Typhimurium (<i>S</i>. Typhimurium), a model human pathogen, across a panel of growth conditions is presented and used in support of our <i>in silico</i> SEP detectability analysis. This integrative approach is used to provide a data-driven census of small proteins expressed by <i>S</i>. Typhimurium across growth phases and infection-relevant conditions. Taken together, our study pinpoints current limitations in proteomics-based detection of novel small proteins currently missing from bacterial genome annotations.</p>","PeriodicalId":74189,"journal":{"name":"microLife","volume":"3 ","pages":"uqac005"},"PeriodicalIF":0.0,"publicationDate":"2022-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9521981","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}

{"title":"It is a matter of whether we allow microbes to enter the food chain.","authors":"","doi":"10.1093/femsml/uqac021","DOIUrl":"https://doi.org/10.1093/femsml/uqac021","url":null,"abstract":"When Martin Loessner decided as a little boy to become a scientist, he was already showing a lot of resistance. Even during Carnival—the so-called ‘Fifth Season’ in the western parts of Germany celebrated with street parades and costume balls—he gave his mum ‘a hard time finding costumes to dress him (me) up as a researcher or explorer’. Since then, Martin followed his curiosity and studied biology in Freiburg i. Br., Germany, and Michigan, USA, and eventually embarked on a PhD at the Bacteriological Institute at the Technical University in Munich, Germany. Here, he further stayed as a postdoctoral researcher, habilitated and became an Assistant Professor. During his early research years, he discovered his passion for bacteriophages and how they interact with their bacterial hosts. Especially, the function of the bacterial cell envelope in the uptake and release of bacteriophages fascinated him and he was at the forefront of research into endolysins (Loessner et al. 1995). These enzymes are encoded by the bacteriophage and activated at the end of the phage multiplication cycle. At that stage, new phage particles are assembled inside the bacterial cells and the bacteria start producing endolysins. With that, they decide their own fate: the endolysin recognizes the peptidoglycan of the bacterial envelope while its catalytic domain hydrolyses the cell wall from within. Together with a membrane pore-forming holin, endolysin activity destroys the host bacterium to release the newly produced phage particles (Loessner et al. 1997). Having found ‘a new agent that works as an antimicrobial, the next question you ask is: What about resistance?’. The answer to that question was unexpected. Since endolysins target highly conserved bonds within the cell wall (Korndörfer et al. 2006), bacteria are essentially unable to modify them, which prevents them from developing resistance. As any microbiologist can imagine, the discovery of a lack of resistance to an effective antibacterial agent can be mind-blowing. So, Martin had to withstand opposing opinions from many researchers and colleagues from the field. However, up to this day, it seems to be worth the effort; researchers have not been able to find any stable bacterial resistance mechanism to endolysins. Applying phages to improve lives","PeriodicalId":74189,"journal":{"name":"microLife","volume":"3 ","pages":"uqac021"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/71/uqac021.PMC10117865.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517169","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}