{"title":"Correction to \"Galactomannan Utilization by Cellvibrio japonicus Relies on a Single Essential α-Galactosidase Encoded by the aga27A Gene\".","authors":"","doi":"10.1111/mmi.15372","DOIUrl":"10.1111/mmi.15372","url":null,"abstract":"","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"102"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xingru Chen, Emily Perez, Eleanor C. Scheeres, Rosemary Northcote, Aretha Fiebig, Andrew J. Olive, Sean Crosson
{"title":"An HWE‐Family Histidine Kinase Modulates Brucella Cell Envelope Properties and Host Innate Immune Response","authors":"Xingru Chen, Emily Perez, Eleanor C. Scheeres, Rosemary Northcote, Aretha Fiebig, Andrew J. Olive, Sean Crosson","doi":"10.1111/mmi.70006","DOIUrl":"https://doi.org/10.1111/mmi.70006","url":null,"abstract":"The bacterial cell envelope is essential for viability and host interaction. In the intracellular pathogen <jats:styled-content style=\"fixed-case\"><jats:italic>Brucella ovis</jats:italic></jats:styled-content>, the orphan HWE‐family histidine kinase PhyK has been implicated in processes that influence cell envelope homeostasis, yet its function remains largely uncharacterized. We show that deletion of <jats:italic>phyK</jats:italic> (∆<jats:italic>phyK</jats:italic>) disrupts cell size control, increases resistance to anionic detergents, enhances sensitivity to cationic envelope disruptors, and triggers broad transcriptional changes, including reduced expression of aerobic respiration genes and increased expression of genes involved in transport and lipid metabolism. This transcriptional profile mirrors that of wild‐type <jats:styled-content style=\"fixed-case\"><jats:italic>B. ovis</jats:italic></jats:styled-content> exposed to an anionic detergent, indicating that loss of PhyK function primes cells to resist this stress. Despite its altered cell envelope properties, the ∆<jats:italic>phyK</jats:italic> mutant exhibits no fitness defect in ex vivo macrophage infection models. However, it elicits a significantly reduced pro‐inflammatory cytokine response in activated murine macrophages compared to the wild‐type strain. We further show that purified PhyK can form multiple stable oligomeric species in solution, reflecting the structural plasticity observed in other HWE‐family kinases and likely contributing to its signaling function in vivo. Our results establish PhyK as a key regulator of <jats:styled-content style=\"fixed-case\"><jats:italic>B. ovis</jats:italic></jats:styled-content> cell envelope properties that can modulate host immune interactions.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"643 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tiffany M. Zarrella, Jianle Gao, Nathan Forrest, Elijah Crosbourne, Kaibo Cui, Guangchun Bai
{"title":"Cyclic Di‐AMP Affects Cell Membrane Integrity of Streptococcus pneumoniae","authors":"Tiffany M. Zarrella, Jianle Gao, Nathan Forrest, Elijah Crosbourne, Kaibo Cui, Guangchun Bai","doi":"10.1111/mmi.70003","DOIUrl":"https://doi.org/10.1111/mmi.70003","url":null,"abstract":"Competence is an important bioprocess for <jats:styled-content style=\"fixed-case\"><jats:italic>Streptococcus pneumoniae</jats:italic></jats:styled-content>. Previously, we demonstrated that the bacterial second messenger cyclic di‐adenosine monophosphate (c‐di‐AMP) modulates pneumococcal competence. Surprisingly, <jats:italic>cdaA*</jats:italic>, a strain producing less c‐di‐AMP due to a point mutation in the diadenylate cyclase CdaA, is susceptible to competence‐stimulating peptide (CSP). In this study, we screened <jats:italic>cdaA</jats:italic>* suppressor mutants resistant to CSP to explore the underlying mechanism. Of 14 clones sequenced, nine clones possessed mutations in the c‐di‐AMP phosphodiesterase Pde1, indicating that the susceptibility to CSP of the <jats:italic>cdaA</jats:italic>* strain is correlated to c‐di‐AMP levels. Another two clones exhibited a mutation in FabT, a transcription factor controlling cell membrane fatty acid biosynthesis. We further showed that deletion of <jats:italic>fabT</jats:italic>, disruption of the FabT‐binding site within the P<jats:sub><jats:italic>fabK</jats:italic></jats:sub> promoter, deletion of a <jats:italic>fabT</jats:italic> activator BriC, or disruption of K<jats:sup>+</jats:sup> uptake in the <jats:italic>cdaA</jats:italic>* mutant all rescued the growth defect of the <jats:italic>cdaA</jats:italic>* strain in media supplemented with CSP. Finally, we found that a c‐di‐AMP phosphodiesterase‐null mutant with high levels of c‐di‐AMP is highly sensitive to treatment with either ethanol or Triton X‐100, which could be corrected by reducing c‐di‐AMP levels through introducing point mutations in CdaA. Together, these findings indicate that c‐di‐AMP affects cell membrane integrity.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"10 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingjing Li, Nora E. Schmitte, Kaya Törkel, Christiane Dahl
{"title":"In Hyphomicrobium denitrificans Two Related Sulfane‐Sulfur Responsive Transcriptional Repressors Regulate Thiosulfate Oxidation and Have a Deep Impact on Nitrate Respiration and Anaerobic Biosyntheses","authors":"Jingjing Li, Nora E. Schmitte, Kaya Törkel, Christiane Dahl","doi":"10.1111/mmi.70002","DOIUrl":"https://doi.org/10.1111/mmi.70002","url":null,"abstract":"Bacteria have evolved multiple strategies to sense and respond to the availability of inorganic reduced sulfur compounds such as thiosulfate. In <jats:styled-content style=\"fixed-case\"><jats:italic>Hyphomicrobium denitrificans</jats:italic></jats:styled-content>, an obligately chemoorganoheterotrophic Alphaproteobacterium, the use of thiosulfate as a supplemental electron donor is regulated by two homologous sulfane‐sulfur‐responsive ArsR‐type transcriptional repressors, sHdrR and SoxR. Here, we provide information on the distribution and phylogeny of sHdrR, the relevance of its two conserved cysteines in vivo, and identify the genes controlled by SoxR and sHdrR not only by targeted qRT‐PCR but also by global RNA‐Seq‐based analyses of regulator‐deficient mutant strains. The absence of sHdrR and SoxR affected 165 and 170 genes, respectively, with 138 genes overlapping. SoxR regulates the <jats:italic>sox</jats:italic> genes for periplasmic thiosulfate oxidation and sulfane sulfur import into the cytoplasm, as well as the <jats:italic>lip‐shdr‐lbpA</jats:italic> genes encoding the cytoplasmic enzymes essential for sulfite formation. sHdrR affects only a subset of these genes. The transcription of <jats:italic>sox</jats:italic> genes remains unaltered in its absence. sHdrR and SoxR act cooperatively and their activity probably also involves interaction with other transcriptional regulators. Most importantly, sHdrR/SoxR regulation extends far beyond sulfur oxidation and deeply affects anaerobic metabolism, particularly denitrification in <jats:styled-content style=\"fixed-case\"><jats:italic>H. denitrificans</jats:italic></jats:styled-content>.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"630 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to ‘TasA Fibre Interactions Are Necessary for Bacillus subtilis Biofilm Structure’","authors":"","doi":"10.1111/mmi.70004","DOIUrl":"https://doi.org/10.1111/mmi.70004","url":null,"abstract":"","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"9 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xingru Chen, Emily Perez, Eleanor C Scheeres, Rosemary Northcote, Aretha Fiebig, Andrew J Olive, Sean Crosson
{"title":"An HWE-Family Histidine Kinase Modulates Brucella Cell Envelope Properties and Host Innate Immune Response.","authors":"Xingru Chen, Emily Perez, Eleanor C Scheeres, Rosemary Northcote, Aretha Fiebig, Andrew J Olive, Sean Crosson","doi":"10.1111/mmi.70006","DOIUrl":"10.1111/mmi.70006","url":null,"abstract":"<p><p>The bacterial cell envelope is essential for viability and host interaction. In the intracellular pathogen Brucella ovis, the orphan HWE-family histidine kinase PhyK has been implicated in processes that influence cell envelope homeostasis, yet its function remains largely uncharacterized. We show that deletion of phyK (∆phyK) disrupts cell size control, increases resistance to anionic detergents, enhances sensitivity to cationic envelope disruptors, and triggers broad transcriptional changes, including reduced expression of aerobic respiration genes and increased expression of genes involved in transport and lipid metabolism. This transcriptional profile mirrors that of wild-type B. ovis exposed to an anionic detergent, indicating that loss of PhyK function primes cells to resist this stress. Despite its altered cell envelope properties, the ∆phyK mutant exhibits no fitness defect in ex vivo macrophage infection models. However, it elicits a significantly reduced pro-inflammatory cytokine response in activated murine macrophages compared to the wild-type strain. We further show that purified PhyK can form multiple stable oligomeric species in solution, reflecting the structural plasticity observed in other HWE-family kinases and likely contributing to its signaling function in vivo. Our results establish PhyK as a key regulator of B. ovis cell envelope properties that can modulate host immune interactions.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natalia de Miguel, María Carolina Touz, Manuela Blasco Pedreros, Gabriel Luna Pizarro
{"title":"Understanding Cell Communication Among Protozoan Parasites","authors":"Natalia de Miguel, María Carolina Touz, Manuela Blasco Pedreros, Gabriel Luna Pizarro","doi":"10.1111/mmi.70005","DOIUrl":"https://doi.org/10.1111/mmi.70005","url":null,"abstract":"Infections caused by single‐celled protozoan parasites affect countless individuals around the world, particularly in low‐ and middle‐income countries. Despite the significant impact on global health, available therapeutic intervention strategies are still limited. Gaining insight into the mechanisms of infection is essential for developing new vaccines and drug therapies. While host–parasite interactions are well‐recognized as critical factors in disease, recent evidence highlights the growing importance of communication among parasites. Various studies indicate that protozoans can interact and communicate with one another, facilitating coordinated behaviors and the emergence of specialized roles within their populations. These interactions help optimize survival strategies and strengthen their response to infections. This review explores how communication among parasites influences social activities, physiological processes, and disease progression.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"22 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adrian Jinich, Anisha Zaveri, Michael A. DeJesus, Amanda Spencer, Ricardo Almada‐Monter, Emanuel Flores‐Bautista, Clare M. Smith, Christopher M. Sassetti, Jeremy M. Rock, Sabine Ehrt, Dirk Schnappinger, Thomas R. Ioerger, Kyu Y. Rhee
{"title":"The Mycobacterium tuberculosis Transposon Sequencing Database (MtbTnDB): A Large‐Scale Guide to Genetic Conditional Essentiality","authors":"Adrian Jinich, Anisha Zaveri, Michael A. DeJesus, Amanda Spencer, Ricardo Almada‐Monter, Emanuel Flores‐Bautista, Clare M. Smith, Christopher M. Sassetti, Jeremy M. Rock, Sabine Ehrt, Dirk Schnappinger, Thomas R. Ioerger, Kyu Y. Rhee","doi":"10.1111/mmi.15370","DOIUrl":"https://doi.org/10.1111/mmi.15370","url":null,"abstract":"Characterizing genetic essentiality across various conditions is fundamental for understanding gene function. Transposon sequencing (TnSeq) is a powerful technique to generate genome‐wide essentiality profiles in bacteria and has been extensively applied to <jats:styled-content style=\"fixed-case\"><jats:italic>Mycobacterium tuberculosis</jats:italic></jats:styled-content> (<jats:italic>Mtb</jats:italic>). Dozens of TnSeq screens have yielded valuable insights into the biology of <jats:italic>Mtb</jats:italic> in vitro, inside macrophages, and in model host organisms. Despite their value, these <jats:italic>Mtb</jats:italic> TnSeq profiles have not been standardized or collated into a single, easily searchable database. This results in significant challenges when attempting to query and compare these resources, limiting our ability to obtain a comprehensive and consistent understanding of genetic conditional essentiality in <jats:italic>Mtb</jats:italic>. We address this problem by building a central repository of publicly available <jats:italic>Mtb</jats:italic> TnSeq screens, the <jats:italic>Mtb</jats:italic> transposon sequencing database (MtbTnDB). The MtbTnDB is a living resource that encompasses to date ≈150 standardized TnSeq screens, enabling open access to data, visualizations, and functional predictions through an interactive web app (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"http://www.mtbtndb.app\">www.mtbtndb.app</jats:ext-link>). We conduct several statistical analyses on the complete database, such as demonstrating that (i) genes in the same genomic neighborhood have similar TnSeq profiles, and (ii) clusters of genes with similar TnSeq profiles are enriched for genes from similar functional categories. We further analyze the performance of machine learning models trained on TnSeq profiles to predict the functional annotation of orphan genes in <jats:italic>Mtb</jats:italic>. By facilitating the comparison of TnSeq screens across conditions, the MtbTnDB will accelerate the exploration of conditional genetic essentiality, provide insights into the functional organization of <jats:italic>Mtb</jats:italic> genes, and help predict gene function in this important human pathogen.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"14 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anshu Chauhan, Hans Carolus, Dimitrios Sofras, Mohit Kumar, Praveen Kumar, Remya Nair, Aswathy Narayanan, Kusum Yadav, Basharat Ali, Vladislav Biriukov, Amandeep Saini, Ian Leaves, Rudy Vergauwen, Celia Lobo Romero, Dhara Malavia-Jones, Ashutosh Singh, Atanu Banerjee, Shivaprakash M. Rudramurthy, Arunaloke Chakrabarti, Alok K. Mondal, Naseem A. Gaur, Kaustuv Sanyal, Jeffrey M. Rybak, Toni Gabaldón, Patrick Van Dijck, Neil A. R. Gow, Rajendra Prasad
{"title":"Multi-Omics Analysis of Experimentally Evolved Candida auris Isolates Reveals Modulation of Sterols, Sphingolipids, and Oxidative Stress in Acquired Amphotericin B Resistance","authors":"Anshu Chauhan, Hans Carolus, Dimitrios Sofras, Mohit Kumar, Praveen Kumar, Remya Nair, Aswathy Narayanan, Kusum Yadav, Basharat Ali, Vladislav Biriukov, Amandeep Saini, Ian Leaves, Rudy Vergauwen, Celia Lobo Romero, Dhara Malavia-Jones, Ashutosh Singh, Atanu Banerjee, Shivaprakash M. Rudramurthy, Arunaloke Chakrabarti, Alok K. Mondal, Naseem A. Gaur, Kaustuv Sanyal, Jeffrey M. Rybak, Toni Gabaldón, Patrick Van Dijck, Neil A. R. Gow, Rajendra Prasad","doi":"10.1111/mmi.15379","DOIUrl":"https://doi.org/10.1111/mmi.15379","url":null,"abstract":"Clinical isolates of <i>Candida auris</i> show a high prevalence of resistance to Amphotericin B (AmB)—an uncommon trait in most <i>Candida</i> species. Alterations in ergosterol biosynthesis can contribute to acquired AmB resistance in <i>C. auris</i> laboratory strains but are rarely seen in clinical isolates. In this study, we experimentally evolved two drug-susceptible Clade II isolates of <i>C. auris</i> to develop AmB resistance. The evolved strains displayed a four to eight fold increase in MIC<sub>50</sub> compared to the parental cells. We analyzed changes in their karyotype, genome, lipidome, and transcriptome associated with this acquired resistance. In one lineage, <i>AOX2</i> was upregulated, and its deletion reversed the AmB resistance phenotype. The <i>aox2Δ</i> mutant also failed to evolve AmB resistance under experimental conditions. In the same lineage, restoring the <i>UPC2</i><sup><i>S332R</i></sup> <i>and RTG3</i><sup><i>S101T</i></sup> mutations to the wild-type allele restored AmB susceptibility. In another lineage, the ergosterol and sphingolipid pathways were observed to play a critical role, and upregulation of the ERG genes elevated the total sterol content, while significant downregulation of <i>HSX11</i> (glucosylceramide synthase) resulted in lower levels of glucosylceramides. To our knowledge, this study is the first to show that AmB resistance in <i>C. auris</i> can be acquired through mechanisms both dependent on or independent of sterol content modulation, highlighting Aox2 and Upc2 as key regulators of amphotericin resistance.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"102 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"FlhG Cooperates With the Cell Cycle Regulator GpsB to Confine Peritrichous Flagella in B. subtilis.","authors":"Anita Dornes,Patrica Bedrunka,Benjamin Pillet,Dieter Kressler,Thomas Heimerl,Jan Pané-Farré,Gert Bange","doi":"10.1111/mmi.15375","DOIUrl":"https://doi.org/10.1111/mmi.15375","url":null,"abstract":"Number and arrangement of flagella, the bacterial locomotion organelles, are species-specific and serve as key taxonomic markers. The FlhG ATPase (also: YlxH, FleN), along with FlhF, plays pivotal roles in determining flagellation patterns. In Bacillus subtilis, FlhG and FlhF govern the spatial arrangement of peritrichous flagella. FlhG aids in flagellar assembly by interacting with the flagellar C-ring protein FliY, yet the molecular implications of this interaction have been unclear. Our study reveals that the ATP-dependent FlhG homodimer interacts with the C-terminal domain of GpsB, a cell cycle regulator, which recruits the peptidoglycan synthase PBP1 (also: ponA) to sites of cell wall elongation. A deletion of gpsB leads to dysregulation of the flagellation pattern mimicking the effects of a flhG deletion strain. The finding that GpsB can interact simultaneously with FlhG and PBP1, combined with the observation that GpsB and FliY can simultaneously interact with FlhG, strongly argues for a model in which FlhG confines flagella biosynthesis to regions of active cell wall biosynthesis. Thus, the FlhG-GpsB interaction appears to enable the locally restrained stimulation of the GTPase FlhF, known for its role to localize flagella in various bacterial species.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"83 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}