Molecular biology and evolution最新文献

{"title":"Reconstruction of Ancestral Protein Sequences Using Autoregressive Generative Models.","authors":"Matteo De Leonardis, Andrea Pagnani, Pierre Barrat-Charlaix","doi":"10.1093/molbev/msaf070","DOIUrl":"10.1093/molbev/msaf070","url":null,"abstract":"<p><p>Ancestral sequence reconstruction (ASR) is an important tool to understand how protein structure and function changed over the course of evolution. It essentially relies on models of sequence evolution that can quantitatively describe changes in a sequence over time. Such models usually consider that sequence positions evolve independently from each other and neglect epistasis: the context-dependence of the effect of mutations. On the other hand, the last years have seen major developments in the field of generative protein models, which learn constraints associated with structure and function from large ensembles of evolutionarily related proteins. Here, we show that it is possible to extend a specific type of generative model to describe the evolution of sequences in time while taking epistasis into account. We apply the developed technique to the problem of ASR: given a protein family and its evolutionary tree, we try to infer the sequences of extinct ancestors. Using both simulations and data coming from experimental evolution we show that our method outperforms state-of-the-art ones. Moreover, it allows for sampling a greater diversity of potential ancestors, allowing for a less biased characterization of ancestral sequences.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localized Tissue-Specific Gene Expression and Gene Duplications are Important Sources of Social Morph Differences in a Social Bumblebee.","authors":"Hongfei Xu, Thomas J Colgan","doi":"10.1093/molbev/msaf063","DOIUrl":"10.1093/molbev/msaf063","url":null,"abstract":"<p><p>Understanding the expression of multiple behaviorally and morphologically distinct phenotypes from a single genome represents a fundamental topic in evolutionary biology. Central to the complication of expressing phenotypes, which may differ in their optima, is the sharing of largely the same genome, which is predicted to manifest in conflict at the genomic level. This is particularly true for social insects where molecular mechanisms, such as differential gene expression, contribute to observed phenotypic differences between reproductive and nonreproductive morphs. In comparison, other mechanisms, such as tissue-specific expression and gene duplications, have been posited as contributing to social morph differences yet formal investigations are limited. Here, using a combination of transcriptomics for multiple tissues and comparative genomics, we show that in a social bumblebee, the strongest differences in gene expression are found in reproductive tissues, such as the spermatheca, an organ previously believed as vestigial in workers but recently shown as functional. In comparison, we find modest expression differences in genes between queens and workers for the brain, fat body, and ovary, which are traditionally investigated in social evolution. Interestingly, morph-biased genes in these three tissues display higher tissue-specificity suggesting that while social morphs may express a shared core transcriptome, localized expression profiles may contribute to phenotypic differences. We also find evidence of differential usage of duplicated genes by queens and workers, highlighting structural variants as a contributing factor to morph differences. Collectively, our findings highlight how social insects can utilize tissue-specific gene regulation and structural variants to contribute to phenotypic differences.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Road to Extinction? Past and Present Population Structure and Genomic Diversity in the Koala.","authors":"Binia De Cahsan, Marcela Sandoval Velasco, Michael V Westbury, David A Duchêne, Mikkel H Strander Sinding, Hernán E Morales, Daniela C Kalthoff, Ian Barnes, Selina Brace, Roberto Portela Miguez, Alfred L Roca, Alex D Greenwood, Rebecca N Johnson, Matthew J Lott, M Thomas P Gilbert","doi":"10.1093/molbev/msaf057","DOIUrl":"10.1093/molbev/msaf057","url":null,"abstract":"<p><p>Koalas are arboreal herbivorous marsupials, endemic to Australia. During the late 1800s and early 1900s, the number of koalas declined dramatically due to hunting for their furs. In addition, anthropogenic activities have further decimated their available habitat, and decreased population numbers. Here, we utilize 37 historic and 25 modern genomes sampled from across their historic and present geographic range, to gain insights into how their population structure and genetic diversity have changed across time; assess the genetic consequences of the period of intense hunting, and the current genetic status of this iconic Australian species. Our analyses reveal how genome-wide heterozygosity has decreased through time and unveil previously uncharacterized mitochondrial haplotypes and nuclear genotypes in the historic dataset, which are absent from today's koala populations.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-by-environment Interactions and Adaptive Body Size Variation in Mice From the Americas.","authors":"Katya L Mack, Nico P Landino, Mariia Tertyshnaia, Tiffany C Longo, Sebastian A Vera, Lilia A Crew, Kristi McDonald, Megan Phifer-Rixey","doi":"10.1093/molbev/msaf078","DOIUrl":"10.1093/molbev/msaf078","url":null,"abstract":"<p><p>The relationship between genotype and phenotype is often mediated by the environment. Moreover, gene-by-environment (GxE) interactions can contribute to variation in phenotypes and fitness. In the last 500 yr, house mice have invaded the Americas. Despite their short residence time, there is evidence of rapid climate adaptation, including shifts in body size and aspects of metabolism with latitude. Previous selection scans have identified candidate genes for metabolic adaptation. However, environmental variation in diet as well as GxE interactions likely impact body mass variation in wild populations. Here, we investigated the role of the environment and GxE interactions in shaping adaptive phenotypic variation. Using new locally adapted inbred strains from North and South America, we evaluated response to a high-fat diet, finding that sex, strain, diet, and the interaction between strain and diet contributed significantly to variation in body size. We also found that the transcriptional response to diet is largely strain-specific, indicating that GxE interactions affecting gene expression are pervasive. Next, we used crosses between strains from contrasting climates to characterize gene expression regulatory divergence on a standard diet and on a high-fat diet. We found that gene regulatory divergence is often condition-specific, particularly for trans-acting changes. Finally, we found evidence for lineage-specific selection on cis-regulatory variation involved in diverse processes, including lipid metabolism. Overlap with scans for selection identified candidate genes for environmental adaptation with diet-specific effects. Together, our results underscore the importance of environmental variation and GxE interactions in shaping adaptive variation in complex traits.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining the Limits of Functional Continuity in the Early Evolution of P-Loop NTPases.","authors":"Andrey O Demkiv, Saacnicteh Toledo-Patiño, Encarnación Medina-Carmona, Andrej Berg, Gaspar P Pinto, Antonietta Parracino, Jose M Sanchez-Ruiz, Alvan C Hengge, Paola Laurino, Liam M Longo, Shina Caroline Lynn Kamerlin","doi":"10.1093/molbev/msaf055","DOIUrl":"10.1093/molbev/msaf055","url":null,"abstract":"<p><p>At the heart of many nucleoside triphosphatases is a conserved phosphate-binding sequence motif. A current model of early enzyme evolution proposes that this six to eight residue motif could have sparked the emergence of the very first nucleoside triphosphatases-a striking example of evolutionary continuity from simple beginnings, if true. To test this provocative model, seven disembodied Walker A-derived peptides were extensively computationally characterized. Although dynamic flickers of nest-like conformations were observed, significant structural similarity between the situated peptide and its disembodied counterpart was not detected. Simulations suggest that phosphate binding is nonspecific, with a preference for GTP over orthophosphate. Control peptides with the same amino acid composition but different sequences and situated conformations behaved similarly to the Walker A peptides, revealing no indication that the Walker A sequence is privileged as a disembodied peptide. We conclude that the evolutionary history of the P-loop NTPase family is unlikely to have started with a disembodied Walker A peptide in an aqueous environment. The limits of evolutionary continuity for this protein family must be reconsidered. Finally, we argue that motifs such as the Walker A motif may represent incomplete or fragmentary molecular fossils-the true nature of which has been eroded by time.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of a Plasmid Regulatory Circuit Ameliorates Plasmid Fitness Cost.","authors":"Clinton A Elg, Erin Mack, Michael Rolfsmeier, Thomas C McLean, David Sneddon, Olivia Kosterlitz, Elizabeth Soderling, Solana Narum, Paul A Rowley, Jack Sullivan, Christopher M Thomas, Eva M Top","doi":"10.1093/molbev/msaf062","DOIUrl":"10.1093/molbev/msaf062","url":null,"abstract":"<p><p>Plasmids promote adaptation of bacteria by facilitating horizontal transfer of diverse genes, notably those conferring antibiotic resistance. Some plasmids, like those of the incompatibility group IncP-1, are known to replicate and persist in a broad range of bacteria. We investigated a poorly understood exception, the IncP-1β plasmid pBP136 from a clinical Bordetella pertussis isolate, which quickly became extinct in laboratory Escherichia coli populations. Through experimental evolution, we found that the inactivation of a previously uncharacterized plasmid gene, upf31, drastically improved plasmid persistence in E. coli. The gene inactivation caused alterations in the plasmid regulatory system, including decreased transcription of the global plasmid regulators (korA, korB, and korC) and numerous genes in their regulons. This is consistent with our findings that Upf31 represses its own transcription. It also caused secondary transcriptional changes in many chromosomal genes. In silico analyses predicted that Upf31 interacts with the plasmid regulator KorB at its C-terminal dimerization domain (CTD). We showed experimentally that adding the CTD of upf31/pBP136 to the naturally truncated upf31 allele of the stable IncP-1β archetype R751 results in plasmid destabilization in E. coli. Moreover, mutagenesis showed that upf31 alleles encoded on nearly half of the sequenced IncP-1β plasmids also possess this destabilization phenotype. While Upf31 might be beneficial in many hosts, we show that in E. coli some alleles have harmful effects that can be rapidly alleviated with a single mutation. Thus, broad-host-range plasmid adaptation to new hosts can involve fine-tuning their transcriptional circuitry through evolutionary changes in a single gene.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phyloformer: Fast, Accurate, and Versatile Phylogenetic Reconstruction with Deep Neural Networks.","authors":"Luca Nesterenko, Luc Blassel, Philippe Veber, Bastien Boussau, Laurent Jacob","doi":"10.1093/molbev/msaf051","DOIUrl":"10.1093/molbev/msaf051","url":null,"abstract":"<p><p>Phylogenetic inference aims at reconstructing the tree describing the evolution of a set of sequences descending from a common ancestor. The high computational cost of state-of-the-art maximum likelihood and Bayesian inference methods limits their usability under realistic evolutionary models. Harnessing recent advances in likelihood-free inference and geometric deep learning, we introduce Phyloformer, a fast and accurate method for evolutionary distance estimation and phylogenetic reconstruction. Sampling many trees and sequences under an evolutionary model, we train the network to learn a function that enables predicting a tree from a multiple sequence alignment. On simulated data, we compare Phyloformer to FastME-a distance method-and two maximum likelihood methods: FastTree and IQTree. Under a commonly used model of protein sequence evolution and exploiting graphics processing unit (GPU) acceleration, Phyloformer outpaces all other approaches and exceeds their accuracy in the Kuhner-Felsenstein metric that accounts for both the topology and branch lengths. In terms of topological accuracy alone, Phyloformer outperforms FastME, but falls behind maximum likelihood approaches, especially as the number of sequences increases. When a model of sequence evolution that includes dependencies between sites is used, Phyloformer outperforms all other methods across all metrics on alignments with fewer than 80 sequences. On 3,801 empirical gene alignments from five different datasets, Phyloformer matches the topological accuracy of the two maximum likelihood implementations. Our results pave the way for the adoption of sophisticated realistic models for phylogenetic inference.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Segregating Structural Variant Defines Novel Venom Phenotypes in the Eastern Diamondback Rattlesnake.","authors":"Pedro G Nachtigall, Gunnar S Nystrom, Emilie M Broussard, Kenneth P Wray, Inácio L M Junqueira-de-Azevedo, Christopher L Parkinson, Mark J Margres, Darin R Rokyta","doi":"10.1093/molbev/msaf058","DOIUrl":"10.1093/molbev/msaf058","url":null,"abstract":"<p><p>Of all mutational mechanisms contributing to phenotypic variation, structural variants are both among the most capable of causing major effects as well as the most technically challenging to identify. Intraspecific variation in snake venoms is widely reported, and one of the most dramatic patterns described is the parallel evolution of streamlined neurotoxic rattlesnake venoms from hemorrhagic ancestors by means of deletion of snake venom metalloproteinase (SVMP) toxins and recruitment of neurotoxic dimeric phospholipase A2 (PLA2) toxins. While generating a haplotype-resolved, chromosome-level genome assembly for the eastern diamondback rattlesnake (Crotalus adamanteus), we discovered that our genome animal was heterozygous for a ∼225 Kb deletion containing six SVMP genes, paralleling one of the two steps involved in the origin of neurotoxic rattlesnake venoms. Range-wide population-genomic analysis revealed that, although this deletion is rare overall, it is the dominant homozygous genotype near the northwestern periphery of the species' range, where this species is vulnerable to extirpation. Although major SVMP deletions have been described in at least five other rattlesnake species, C. adamanteus is unique in not additionally gaining neurotoxic PLA2s. Previous work established a superficially complementary north-south gradient in myotoxin (MYO) expression based on copy number variation with high expression in the north and low in the south, yet we found that the SVMP and MYO genotypes vary independently, giving rise to an array of diverse, novel venom phenotypes across the range. Structural variation, therefore, forms the basis for the major axes of geographic venom variation for C. adamanteus.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Robustness of Ancestral Sequence Reconstruction to Among-site and Among-lineage Evolutionary Heterogeneity.","authors":"Ricardo Muñiz-Trejo, Yeonwoo Park, Joseph W Thornton","doi":"10.1093/molbev/msaf084","DOIUrl":"10.1093/molbev/msaf084","url":null,"abstract":"<p><p>Ancestral sequence reconstruction is typically performed using homogeneous evolutionary models, which assume that the same substitution propensities affect all sites and lineages. These assumptions are routinely violated: heterogeneous structural and functional constraints favor different amino acids at different sites, and these constraints often change among lineages as epistatic substitutions accrue at other sites. To evaluate how violations of the homogeneity assumption affect ancestral sequence reconstruction under realistic conditions, we developed site-specific substitution models and parameterized them using data from deep mutational scanning experiments on three protein families; we then used these models to perform ancestral sequence reconstruction on the empirical alignments and on alignments simulated under heterogeneous conditions derived from the experiments. Extensive among-site and -lineage heterogeneity is present in these datasets, but the sequences reconstructed from empirical alignments are almost identical when heterogeneous or homogeneous models are used for ancestral sequence reconstruction. Using models fit to deep mutational scanning data from distantly related proteins in which mutational effects are very different also has a minimal impact on ancestral sequence reconstruction. The rare differences occur primarily where phylogenetic signal is weak-at fast-evolving sites and nodes connected by long branches. When ancestral sequence reconstruction is performed on simulated data, errors in the reconstructed sequences become more likely as branch lengths increase, but incorporating heterogeneity into the model does not improve accuracy. These data establish that ancestral sequence reconstruction is robust to unincorporated realistic forms of evolutionary heterogeneity, because the primary determinant of ancestral sequence reconstruction is phylogenetic signal, not the substitution model. The best way to improve accuracy is therefore not to develop more elaborate models but to apply ancestral sequence reconstruction to densely sampled alignments that maximize phylogenetic signal at the nodes of interest.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 4","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary History of Bilaterian FoxP Genes: Complex Ancestral Functions and Evolutionary Changes Spanning 2R-WGD in the Vertebrate Lineage.","authors":"Fu-Yu Tsai, Che-Yi Lin, Yi-Hsien Su, Jr-Kai Yu, Dian-Han Kuo","doi":"10.1093/molbev/msaf072","DOIUrl":"10.1093/molbev/msaf072","url":null,"abstract":"<p><p>Human and fly FoxP homologs are well-known for their roles in the development of cognitive abilities. These findings have led to the hypothesis that the ancestral function of FoxP was in the development of cognitive neural circuits. However, complex brains in human and fly evolved independently, and the similar cognitive function of FoxP in human and fly may thus be interpreted as a result of convergent evolution. In addition, the 4 gnathostome FoxP paralogs also possess diverse developmental functions unrelated to neurodevelopment, which might have been overlooked in comparative studies of invertebrate FoxP homologs. To resolve these uncertainties, we set out to improve the phylogenetic reconstruction of vertebrate FoxP homologs and broaden the taxonomic sampling of gene expression profiling to include an invertebrate chordate, ambulacrarian deuterostomes, and a spiralian protostome. Using phylogenetic analysis combined with synteny mapping, we elaborated the hypothesis that the 4 FoxP paralogs arose through the 2R-WGD events shared by all gnathostome species. Based on this evolutionary scenario, we examined the FoxP expression pattern in amphioxus development and concluded that FoxP already had complex developmental functions across all germ layers in the chordate ancestor. Moreover, in sea urchin, hemichordate, and catenulid flatworm, FoxP was expressed in the gut prominently, in addition to the anterior neurogenic ectoderm. This surprising similarity shared among these distantly related species implies that FoxP may have a significant function in gut development in addition to the neural development function in the last common ancestor of bilaterians.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}