Nicolas G. Shealy, Madi Baltagulov, Mariana X. Byndloss
{"title":"A long journey to the colon: The role of the small intestine microbiota in intestinal disease","authors":"Nicolas G. Shealy, Madi Baltagulov, Mariana X. Byndloss","doi":"10.1111/mmi.15270","DOIUrl":"https://doi.org/10.1111/mmi.15270","url":null,"abstract":"The small intestine represents a complex and understudied gut niche with significant implications for human health. Indeed, many infectious and non-infectious diseases center within the small intestine and present similar clinical manifestations to large intestinal disease, complicating non-invasive diagnosis and treatment. One major neglected aspect of small intestinal diseases is the feedback relationship with the resident collection of commensal organisms, the gut microbiota. Studies focused on microbiota–host interactions in the small intestine in the context of infectious and non-infectious diseases are required to identify potential therapeutic targets dissimilar from those used for large bowel diseases. While sparsely populated, the small intestine represents a stringent commensal bacterial microenvironment the host relies upon for nutrient acquisition and protection against invading pathogens (colonization resistance). Indeed, recent evidence suggests that disruptions to host–microbiota interactions in the small intestine impact enteric bacterial pathogenesis and susceptibility to non-infectious enteric diseases. In this review, we focus on the microbiota's impact on small intestine function and the pathogenesis of infectious and non-infectious diseases of the gastrointestinal (GI) tract. We also discuss gaps in knowledge on the role of commensal microorganisms in proximal GI tract function during health and disease.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"154 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817356","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}
Geraldy Lie Stefanus Liman, Andy A Garcia, Kristin A Fluke, Hayden R Anderson, Sarah C Davidson, Paula V Welander, Thomas J Santangelo
{"title":"Tetraether archaeal lipids promote long-term survival in extreme conditions.","authors":"Geraldy Lie Stefanus Liman, Andy A Garcia, Kristin A Fluke, Hayden R Anderson, Sarah C Davidson, Paula V Welander, Thomas J Santangelo","doi":"10.1111/mmi.15240","DOIUrl":"10.1111/mmi.15240","url":null,"abstract":"<p><p>The sole unifying feature of the incredibly diverse Archaea is their isoprenoid-based ether-linked lipid membranes. Unique lipid membrane composition, including an abundance of membrane-spanning tetraether lipids, impart resistance to extreme conditions. Many questions remain, however, regarding the synthesis and modification of tetraether lipids and how dynamic changes to archaeal lipid membrane composition support hyperthermophily. Tetraether membranes, termed glycerol dibiphytanyl glycerol tetraethers (GDGTs), are generated by tetraether synthase (Tes) by joining the tails of two bilayer lipids known as archaeol. GDGTs are often further specialized through the addition of cyclopentane rings by GDGT ring synthase (Grs). A positive correlation between relative GDGT abundance and entry into stationary phase growth has been observed, but the physiological impact of inhibiting GDGT synthesis has not previously been reported. Here, we demonstrate that the model hyperthermophile Thermococcus kodakarensis remains viable when Tes (TK2145) or Grs (TK0167) are deleted, permitting phenotypic and lipid analyses at different temperatures. The absence of cyclopentane rings in GDGTs does not impact growth in T. kodakarensis, but an overabundance of rings due to ectopic Grs expression is highly fitness negative at supra-optimal temperatures. In contrast, deletion of Tes resulted in the loss of all GDGTs, cyclization of archaeol, and loss of viability upon transition to the stationary phase in this model archaea. These results demonstrate the critical roles of highly specialized, dynamic, isoprenoid-based lipid membranes for archaeal survival at high temperatures.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"882-894"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139900188","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}
Maximilian Groß, Beate Dika, Elisabeth Loos, Lala Aliyeva-Schnorr, Holger B Deising
{"title":"The galactose metabolism genes UGE1 and UGM1 are novel virulence factors of the maize anthracnose fungus Colletotrichum graminicola.","authors":"Maximilian Groß, Beate Dika, Elisabeth Loos, Lala Aliyeva-Schnorr, Holger B Deising","doi":"10.1111/mmi.15242","DOIUrl":"10.1111/mmi.15242","url":null,"abstract":"<p><p>Fungal cell walls represent the frontline contact with the host and play a prime role in pathogenesis. While the roles of the cell wall polymers like chitin and branched β-glucan are well understood in vegetative and pathogenic development, that of the most prominent galactose-containing polymers galactosaminogalactan and fungal-type galactomannan is unknown in plant pathogenic fungi. Mining the genome of the maize pathogen Colletotrichum graminicola identified the single-copy key galactose metabolism genes UGE1 and UGM1, encoding a UDP-glucose-4-epimerase and UDP-galactopyranose mutase, respectively. UGE1 is thought to be required for biosynthesis of both polymers, whereas UGM1 is specifically required for fungal-type galactomannan formation. Promoter:eGFP fusion strains revealed that both genes are expressed in vegetative and in pathogenic hyphae at all stages of pathogenesis. Targeted deletion of UGE1 and UGM1, and fluorescence-labeling of galactosaminogalactan and fungal-type galactomannan confirmed that Δuge1 mutants were unable to synthesize either of these polymers, and Δugm1 mutants did not exhibit fungal-type galactomannan. Appressoria of Δuge1, but not of Δugm1 mutants, were defective in adhesion, highlighting a function of galactosaminogalactan in the establishment of these infection cells on hydrophobic surfaces. Both Δuge1 and Δugm1 mutants showed cell wall defects in older vegetative hyphae and severely reduced appressorial penetration competence. On intact leaves of Zea mays, both mutants showed strongly reduced disease symptom severity, indicating that UGE1 and UGM1 represent novel virulence factors of C. graminicola.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"912-926"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940317","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":"The swimming defect caused by the absence of the transcriptional regulator LdtR in Sinorhizobium meliloti is restored by mutations in the motility genes motA and motS.","authors":"Richard C Sobe, Birgit E Scharf","doi":"10.1111/mmi.15247","DOIUrl":"10.1111/mmi.15247","url":null,"abstract":"<p><p>The flagellar motor is a powerful macromolecular machine used to propel bacteria through various environments. We determined that flagellar motility of the alpha-proteobacterium Sinorhizobium meliloti is nearly abolished in the absence of the transcriptional regulator LdtR, known to influence peptidoglycan remodeling and stress response. LdtR does not regulate motility gene transcription. Remarkably, the motility defects of the ΔldtR mutant can be restored by secondary mutations in the motility gene motA or a previously uncharacterized gene in the flagellar regulon, which we named motS. MotS is not essential for S. meliloti motility and may serve an accessory role in flagellar motor function. Structural modeling predicts that MotS comprised an N-terminal transmembrane segment, a long-disordered region, and a conserved β-sandwich domain. The C terminus of MotS is localized in the periplasm. Genetics based substitution of MotA with MotA<sub>G12S</sub> also restored the ΔldtR motility defect. The MotA<sub>G12S</sub> variant protein features a local polarity shift at the periphery of the MotAB stator units. We propose that MotS may be required for optimal alignment of stators in wild-type flagellar motors but becomes detrimental in cells with altered peptidoglycan. Similarly, the polarity shift in stator units composed of MotB/MotA<sub>G12S</sub> might stabilize its interaction with altered peptidoglycan.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"954-970"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065578","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}
Kamal Kumar, Rituparna Basak, Aakansha Rai, Amitabha Mukhopadhyay
{"title":"GRASP negatively regulates the secretion of the virulence factor gp63 in Leishmania.","authors":"Kamal Kumar, Rituparna Basak, Aakansha Rai, Amitabha Mukhopadhyay","doi":"10.1111/mmi.15255","DOIUrl":"10.1111/mmi.15255","url":null,"abstract":"<p><p>Metalloprotease-gp63 is a virulence factor secreted by Leishmania. However, secretory pathway in Leishmania is not well defined. Here, we cloned and expressed the GRASP homolog from Leishmania. We found that Leishmania expresses one GRASP homolog of 58 kDa protein (LdGRASP) which localizes in LdRab1- and LPG2-positive Golgi compartment in Leishmania. LdGRASP was found to bind with COPII complex, LdARF1, LdRab1 and LdRab11 indicating its role in ER and Golgi transport in Leishmania. To determine the function of LdGRASP, we generated LdGRASP knockout parasites using CRISPR-Cas9. We found fragmentation of Golgi in Ld:GRASPKO parasites. Our results showed enhanced transport of non-GPI-anchored gp63 to the cell surface leading to higher secretion of this form of gp63 in Ld:GRASPKO parasites in comparison to Ld:WT cells. In contrast, we found that transport of GPI-anchored gp63 to the cell surface is blocked in Ld:GRASPKO parasites and thereby inhibits its secretion. The overexpression of dominant-negative mutant of LdRab1 or LdSar1 in Ld:GRASPKO parasites significantly blocked the secretion of non-GPI-anchored gp63. Interestingly, we found that survival of transgenic parasites overexpressing Ld:GRASP-GFP is significantly compromised in macrophages in comparison to Ld:WT and Ld:GRASPKO parasites. These results demonstrated that LdGRASP differentially regulates Ldgp63 secretory pathway in Leishmania.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1063-1078"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336278","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}
Geromy G Moore, Brian M Mack, Karen L Wendt, Lina Castano-Duque, Victoria M Anderson, Robert H Cichewicz
{"title":"Genomic and metabolomic diversity within a familial population of Aspergillus flavus.","authors":"Geromy G Moore, Brian M Mack, Karen L Wendt, Lina Castano-Duque, Victoria M Anderson, Robert H Cichewicz","doi":"10.1111/mmi.15244","DOIUrl":"10.1111/mmi.15244","url":null,"abstract":"<p><p>Aspergillus flavus is an agriculturally significant micro-fungus having potential to contaminate food and feed crops with toxic secondary metabolites such as aflatoxin (AF) and cyclopiazonic acid (CPA). Research has shown A. flavus strains can overcome heterokaryon incompatibility and undergo meiotic recombination as teleomorphs. Although evidence of recombination in the AF gene cluster has been reported, the impacts of recombination on genotype and metabolomic phenotype in a single generation are lacking. In previous studies, we paired an aflatoxigenic MAT1-1 A. flavus strain with a non-aflatoxigenic MAT1-2 A. flavus strain that had been tagged with green fluorescent protein and then 10 F1 progenies (a mix of fluorescent and non-fluorescent) were randomly selected from single-ascospore colonies and broadly examined for evidence of recombination. In this study, we determined four of those 10 F1 progenies were recombinants because they were not vegetatively compatible with either parent or their siblings, and they exhibited other distinctive traits that could only result from meiotic recombination. The other six progenies examined shared genomic identity with the non-aflatoxigenic, fluorescent, and MAT1-2 parent, but were metabolically distinct. This study highlights phenotypic and genomic changes that may occur in a single generation from the outcrossing of sexually compatible strains of A. flavus.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"927-939"},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139940315","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}
Zeus Jaren Nair, Iris Hanxing Gao, Aslam Firras, Kelvin Kian Long Chong, Eric D Hill, Pei Yi Choo, Cristina Colomer-Winter, Qingyan Chen, Caroline Manzano, Kevin Pethe, Kimberly A Kline
{"title":"An essential protease, FtsH, influences daptomycin resistance acquisition in Enterococcus faecalis.","authors":"Zeus Jaren Nair, Iris Hanxing Gao, Aslam Firras, Kelvin Kian Long Chong, Eric D Hill, Pei Yi Choo, Cristina Colomer-Winter, Qingyan Chen, Caroline Manzano, Kevin Pethe, Kimberly A Kline","doi":"10.1111/mmi.15253","DOIUrl":"10.1111/mmi.15253","url":null,"abstract":"<p><p>Daptomycin is a last-line antibiotic commonly used to treat vancomycin-resistant Enterococci, but resistance evolves rapidly and further restricts already limited treatment options. While genetic determinants associated with clinical daptomycin resistance (DAP<sup>R</sup>) have been described, information on factors affecting the speed of DAP<sup>R</sup> acquisition is limited. The multiple peptide resistance factor (MprF), a phosphatidylglycerol-modifying enzyme involved in cationic antimicrobial resistance, is linked to DAP<sup>R</sup> in pathogens such as methicillin-resistant Staphylococcus aureus. Since Enterococcus faecalis encodes two paralogs of mprF and clinical DAP<sup>R</sup> mutations do not map to mprF, we hypothesized that functional redundancy between the paralogs prevents mprF-mediated resistance and masks other evolutionary pathways to DAP<sup>R</sup>. Here, we performed in vitro evolution to DAP<sup>R</sup> in mprF mutant background. We discovered that the absence of mprF results in slowed DAP<sup>R</sup> evolution and is associated with inactivating mutations in ftsH, resulting in the depletion of the chaperone repressor HrcA. We also report that ftsH is essential in the parental, but not in the ΔmprF, strain where FtsH depletion results in growth impairment in the parental strain, a phenotype associated with reduced extracellular acidification and reduced ability for metabolic reduction. This presents FtsH and HrcA as enticing targets for developing anti-resistance strategies.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1021-1038"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288521","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}
Nerina Jusufovic, Andrew C Krusenstjerna, Christina R Savage, Timothy C Saylor, Catherine A Brissette, Wolfram R Zückert, Paula J Schlax, Md A Motaleb, Brian Stevenson
{"title":"Borrelia burgdorferi PlzA is a cyclic-di-GMP dependent DNA and RNA binding protein.","authors":"Nerina Jusufovic, Andrew C Krusenstjerna, Christina R Savage, Timothy C Saylor, Catherine A Brissette, Wolfram R Zückert, Paula J Schlax, Md A Motaleb, Brian Stevenson","doi":"10.1111/mmi.15254","DOIUrl":"10.1111/mmi.15254","url":null,"abstract":"<p><p>The PilZ domain-containing protein, PlzA, is the only known cyclic di-GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here, we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of binding c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the major groove of DNA and that sequence length and G-C content play a role in DNA binding affinity. PlzA is a dual-domain protein with a PilZ-like N-terminal domain linked to a canonical C-terminal PilZ domain. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids independently of c-di-GMP. The C-terminal domain, which includes the c-di-GMP binding motifs, did not bind nucleic acids under any tested conditions. Our data are supported by computational docking, which predicts that c-di-GMP binding at the C-terminal domain stabilizes the overall protein structure and facilitates PlzA-DNA interactions via residues in the N-terminal domain. Based on our data, we propose that levels of c-di-GMP during the various stages of the enzootic life cycle direct PlzA binding to regulatory targets.</p>","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":" ","pages":"1039-1062"},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288522","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":"Identification of a 1-acyl-glycerol-3-phosphate acyltransferase from Mycobacterium tuberculosis, a key enzyme involved in triacylglycerol biosynthesis","authors":"Meghna Santoshi, Harsh Bansia, Muzammil Hussain, Abodh Kumar Jha, Valakunja Nagaraja","doi":"10.1111/mmi.15265","DOIUrl":"https://doi.org/10.1111/mmi.15265","url":null,"abstract":"Latent tuberculosis, caused by dormant <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), poses a threat to global health through the incubation of undiagnosed infections within the community. Dormant <i>Mtb</i>, which is phenotypically tolerant to antibiotics, accumulates triacylglycerol (TAG) utilizing fatty acids obtained from macrophage lipid droplets. TAG is vital to mycobacteria, serving as a cell envelope component and energy reservoir during latency. TAG synthesis occurs by sequential acylation of glycerol-3-phosphate, wherein the second acylation step is catalyzed by acylglycerol-3-phosphate acyltransferase (AGPAT), resulting in the production of phosphatidic acid (PA), a precursor for the synthesis of TAG and various phospholipids. Here, we have characterized a putative acyltransferase of <i>Mtb</i> encoded by Rv3816c. We found that Rv3816c has all four characteristic motifs of AGPAT, exists as a membrane-bound enzyme, and functions as 1-acylglycerol-3-phosphate acyltransferase. The enzyme could transfer the acyl group to acylglycerol-3-phosphate (LPA) from monounsaturated fatty acyl-coenzyme A of chain length 16 or 18 to produce PA. Complementation of <i>Escherichia coli</i> PlsC mutant in vivo by Rv3816c confirmed that it functions as AGPAT. Its active site mutants, H43A and D48A, were incapable of transferring the acyl group to LPA in vitro and were not able to rescue the growth defect of <i>E. coli</i> PlsC mutant in vivo. Identifying Rv3816c as AGPAT and comparing its properties with other AGPAT homologs is not only a step toward understanding the TAG biosynthesis in mycobacteria but has the potential to explore it as a drug target.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"9 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651800","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":"House of CarDs: Functional insights into the transcriptional regulator CdnL","authors":"Erika L. Smith, Erin D. Goley","doi":"10.1111/mmi.15268","DOIUrl":"https://doi.org/10.1111/mmi.15268","url":null,"abstract":"Regulation of bacterial transcription is a complex and multi-faceted phenomenon that is critical for growth and adaptation. Proteins in the CarD_CdnL_TRCF family are widespread, often essential, regulators of transcription of genes required for growth and metabolic homeostasis. Research in the last decade has described the mechanistic and structural bases of CarD-CdnL-mediated regulation of transcription initiation. More recently, studies in a range of bacteria have begun to elucidate the physiological roles of CarD-CdnL proteins as well as mechanisms by which these proteins, themselves, are regulated. A theme has emerged wherein regulation of CarD-CdnL proteins is central to bacterial adaptation to stress and/or changing environmental conditions.","PeriodicalId":19006,"journal":{"name":"Molecular Microbiology","volume":"51 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651406","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}