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[PMID]:28985510
[Au] Autor:Montalbano A; Canver MC; Sanjana NE
[Ad] Endereço:New York Genome Center, New York, NY, USA; Department of Biology, New York University, New York, NY, USA.
[Ti] Título:High-Throughput Approaches to Pinpoint Function within the Noncoding Genome.
[So] Source:Mol Cell;68(1):44-59, 2017 Oct 05.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas nuclease system is a powerful tool for genome editing, and its simple programmability has enabled high-throughput genetic and epigenetic studies. These high-throughput approaches offer investigators a toolkit for functional interrogation of not only protein-coding genes but also noncoding DNA. Historically, noncoding DNA has lacked the detailed characterization that has been applied to protein-coding genes in large part because there has not been a robust set of methodologies for perturbing these regions. Although the majority of high-throughput CRISPR screens have focused on the coding genome to date, an increasing number of CRISPR screens targeting noncoding genomic regions continue to emerge. Here, we review high-throughput CRISPR-based approaches to uncover and understand functional elements within the noncoding genome and discuss practical aspects of noncoding library design and screen analysis.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
DNA Intergênico/genética
Endonucleases/genética
Edição de Genes/métodos
Genoma
[Mh] Termos MeSH secundário: Animais
DNA Intergênico/metabolismo
Endonucleases/metabolismo
Células Eucarióticas/citologia
Células Eucarióticas/metabolismo
Engenharia Genética
Biblioteca Genômica
Ensaios de Triagem em Larga Escala
Humanos
RNA Guia/genética
RNA Guia/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (DNA, Intergenic); 0 (RNA, Guide); EC 3.1.- (Endonucleases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171103
[Lr] Data última revisão:
171103
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171006
[St] Status:MEDLINE


  2 / 25087 MEDLINE  
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[PMID]:29053968
[Au] Autor:Bonev B; Mendelson Cohen N; Szabo Q; Fritsch L; Papadopoulos GL; Lubling Y; Xu X; Lv X; Hugnot JP; Tanay A; Cavalli G
[Ad] Endereço:Institute of Human Genetics, UMR 9002 of the CNRS and the Université de Montpellier, 34396 Montpellier, France. Electronic address: boyan.bonev@igh.cnrs.fr.
[Ti] Título:Multiscale 3D Genome Rewiring during Mouse Neural Development.
[So] Source:Cell;171(3):557-572.e24, 2017 Oct 19.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact more strongly. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between neural transcription factors appear in vivo. Finally, cell type-specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development.
[Mh] Termos MeSH primário: Cromatina/metabolismo
Genoma
Neurogênese
[Mh] Termos MeSH secundário: Animais
Células-Tronco Embrionárias/metabolismo
Elementos Facilitadores Genéticos
Éxons
Expressão Gênica
Redes Reguladoras de Genes
Camundongos
Regiões Promotoras Genéticas
Proteínas Repressoras/metabolismo
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CCCTC-binding factor); 0 (Chromatin); 0 (Repressor Proteins); 0 (Transcription Factors)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE


  3 / 25087 MEDLINE  
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[PMID]:29033129
[Au] Autor:Poleshko A; Shah PP; Gupta M; Babu A; Morley MP; Manderfield LJ; Ifkovits JL; Calderon D; Aghajanian H; Sierra-Pagán JE; Sun Z; Wang Q; Li L; Dubois NC; Morrisey EE; Lazar MA; Smith CL; Epstein JA; Jain R
[Ad] Endereço:Departments of Medicine and Cell and Developmental Biology, Institute for Regenerative Medicine, and the Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
[Ti] Título:Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.
[So] Source:Cell;171(3):573-587.e14, 2017 Oct 19.
[Is] ISSN:1097-4172
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery.
[Mh] Termos MeSH primário: Cromatina/metabolismo
Regulação da Expressão Gênica no Desenvolvimento
Histona Desacetilases/metabolismo
Lâmina Nuclear/metabolismo
Células-Tronco/citologia
[Mh] Termos MeSH secundário: Animais
Genoma
Camundongos
Miócitos Cardíacos/citologia
Miócitos Cardíacos/metabolismo
Células-Tronco/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Chromatin); EC 3.5.1.98 (Histone Deacetylases); EC 3.5.1.98 (histone deacetylase 3)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171016
[St] Status:MEDLINE


  4 / 25087 MEDLINE  
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[PMID]:28650343
[Au] Autor:Miles LA; Burga LN; Gardner EE; Bostina M; Poirier JT; Rudin CM
[Ad] Endereço:Molecular Pharmacology Program and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
[Ti] Título:Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus.
[So] Source:J Clin Invest;127(8):2957-2967, 2017 Aug 01.
[Is] ISSN:1558-8238
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. It has shown promise as a cancer therapeutic in preclinical studies and early-phase clinical trials. Here, we have identified anthrax toxin receptor 1 (ANTXR1) as the receptor for SVV using genome-wide loss-of-function screens. ANTXR1 is necessary for permissivity in vitro and in vivo. However, robust SVV replication requires an additional innate immune defect. We found that SVV interacts directly and specifically with ANTXR1, that this interaction is required for SVV binding to permissive cells, and that ANTXR1 expression is necessary and sufficient for infection in cell lines with decreased expression of antiviral IFN genes at baseline. Finally, we identified the region of the SVV capsid that is responsible for receptor recognition using cryoelectron microscopy of the SVV-ANTXR1-Fc complex. These studies identify ANTXR1, a class of receptor that is shared by a mammalian virus and a bacterial toxin, as the cellular receptor for SVV.
[Mh] Termos MeSH primário: Proteínas do Capsídeo/química
Proteínas de Neoplasias/química
Picornaviridae
Receptores de Superfície Celular/química
Receptores Virais/química
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Sobrevivência Celular
Microscopia Crioeletrônica
Feminino
Perfilação da Expressão Gênica
Genoma
Proteínas de Fluorescência Verde/química
Humanos
Camundongos
Camundongos Nus
Terapia Viral Oncolítica
Vírus Oncolíticos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ANTXR1 protein, human); 0 (Capsid Proteins); 0 (Neoplasm Proteins); 0 (Receptors, Cell Surface); 0 (Receptors, Virus); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170626
[St] Status:MEDLINE


  5 / 25087 MEDLINE  
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[PMID]:28505302
[Au] Autor:Mun S; Kim YJ; Markkandan K; Shin W; Oh S; Woo J; Yoo J; An H; Han K
[Ad] Endereço:Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
[Ti] Título:The Whole-Genome and Transcriptome of the Manila Clam (Ruditapes philippinarum).
[So] Source:Genome Biol Evol;9(6):1487-1498, 2017 Jun 01.
[Is] ISSN:1759-6653
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The manila clam, Ruditapes philippinarum, is an important bivalve species in worldwide aquaculture including Korea. The aquaculture production of R. philippinarum is under threat from diverse environmental factors including viruses, microorganisms, parasites, and water conditions with subsequently declining production. In spite of its importance as a marine resource, the reference genome of R. philippinarum for comprehensive genetic studies is largely unexplored. Here, we report the de novo whole-genome and transcriptome assembly of R. philippinarum across three different tissues (foot, gill, and adductor muscle), and provide the basic data for advanced studies in selective breeding and disease control in order to obtain successful aquaculture systems. An approximately 2.56 Gb high quality whole-genome was assembled with various library construction methods. A total of 108,034 protein coding gene models were predicted and repetitive elements including simple sequence repeats and noncoding RNAs were identified to further understanding of the genetic background of R. philippinarum for genomics-assisted breeding. Comparative analysis with the bivalve marine invertebrates uncover that the gene family related to complement C1q was enriched. Furthermore, we performed transcriptome analysis with three different tissues in order to support genome annotation and then identified 41,275 transcripts which were annotated. The R. philippinarum genome resource will markedly advance a wide range of potential genetic studies, a reference genome for comparative analysis of bivalve species and unraveling mechanisms of biological processes in molluscs. We believe that the R. philippinarum genome will serve as an initial platform for breeding better-quality clams using a genomic approach.
[Mh] Termos MeSH primário: Bivalves/genética
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Perfilação da Expressão Gênica/métodos
Marcadores Genéticos
Genoma
Genômica
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Filogenia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Genetic Markers)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170515
[St] Status:MEDLINE
[do] DOI:10.1093/gbe/evx096


  6 / 25087 MEDLINE  
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[PMID]:28236503
[Au] Autor:Tomaszkiewicz M; Medvedev P; Makova KD
[Ad] Endereço:Department of Biology, Pennsylvania State University, University Park, PA 16802, USA.
[Ti] Título:Y and W Chromosome Assemblies: Approaches and Discoveries.
[So] Source:Trends Genet;33(4):266-282, 2017 Apr.
[Is] ISSN:0168-9525
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hundreds of vertebrate genomes have been sequenced and assembled to date. However, most sequencing projects have ignored the sex chromosomes unique to the heterogametic sex - Y and W - that are known as sex-limited chromosomes (SLCs). Indeed, haploid and repetitive Y chromosomes in species with male heterogamety (XY), and W chromosomes in species with female heterogamety (ZW), are difficult to sequence and assemble. Nevertheless, obtaining their sequences is important for understanding the intricacies of vertebrate genome function and evolution. Recent progress has been made towards the adaptation of next-generation sequencing (NGS) techniques to deciphering SLC sequences. We review here currently available methodology and results with regard to SLC sequencing and assembly. We focus on vertebrates, but bring in some examples from other taxa.
[Mh] Termos MeSH primário: Evolução Molecular
Cromossomos Sexuais/genética
Processos de Determinação Sexual
Cromossomo Y/genética
[Mh] Termos MeSH secundário: Animais
Feminino
Genoma
Sequenciamento de Nucleotídeos em Larga Escala
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170225
[St] Status:MEDLINE


  7 / 25087 MEDLINE  
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[PMID]:28861108
[Au] Autor:Razin SV; Ulianov SV
[Ad] Endereço:Institute of Gene Biology, Russian Academy of Sciences, Vavilov Street 34/5, 119334 Moscow, Russia.
[Ti] Título:Gene functioning and storage within a folded genome.
[So] Source:Cell Mol Biol Lett;22:18, 2017.
[Is] ISSN:1689-1392
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In mammals, genomic DNA that is roughly 2 m long is folded to fit the size of the cell nucleus that has a diameter of about 10 µm. The folding of genomic DNA is mediated via assembly of DNA-protein complex, chromatin. In addition to the reduction of genomic DNA linear dimensions, the assembly of chromatin allows to discriminate and to mark active (transcribed) and repressed (non-transcribed) genes. Consequently, epigenetic regulation of gene expression occurs at the level of DNA packaging in chromatin. Taking into account the increasing attention of scientific community toward epigenetic systems of gene regulation, it is very important to understand how DNA folding in chromatin is related to gene activity. For many years the hierarchical model of DNA folding was the most popular. It was assumed that nucleosome fiber (10-nm fiber) is folded into 30-nm fiber and further on into chromatin loops attached to a nuclear/chromosome scaffold. Recent studies have demonstrated that there is much less regularity in chromatin folding within the cell nucleus. The very existence of 30-nm chromatin fibers in living cells was questioned. On the other hand, it was found that chromosomes are partitioned into self-interacting spatial domains that restrict the area of enhancers action. Thus, TADs can be considered as structural-functional domains of the chromosomes. Here we discuss the modern view of DNA packaging within the cell nucleus in relation to the regulation of gene expression. Special attention is paid to the possible mechanisms of the chromatin fiber self-assembly into TADs. We discuss the model postulating that partitioning of the chromosome into TADs is determined by the distribution of active and inactive chromatin segments along the chromosome. This article was specially invited by the editors and represents work by leading researchers.
[Mh] Termos MeSH primário: Cromatina
Empacotamento do DNA
Regulação da Expressão Gênica
Genoma
[Mh] Termos MeSH secundário: Animais
Núcleo Celular
Humanos
Mamíferos/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Chromatin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1186/s11658-017-0050-4


  8 / 25087 MEDLINE  
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[PMID]:28430982
[Au] Autor:Herai RH; Negraes PD; Muotri AR
[Ad] Endereço:Department of Pediatrics/Rady Children's Hospital San Diego, Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093, MC 0695, USA.
[Ti] Título:Evidence of nuclei-encoded spliceosome mediating splicing of mitochondrial RNA.
[So] Source:Hum Mol Genet;26(13):2472-2479, 2017 Jul 01.
[Is] ISSN:1460-2083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Mitochondria are thought to have originated as free-living prokaryotes. Mitochondria organelles have small circular genomes with substantial structural and genetic similarity to bacteria. Contrary to the prevailing concept of intronless mitochondria, here we present evidence that mitochondrial RNA transcripts (mtRNA) are not limited to policystronic molecules, but also processed as nuclei-like transcripts that are differentially spliced and expressed in a cell-type specific manner. The presence of canonical splice sites in the mtRNA introns and of core components of the nuclei-encoded spliceosome machinery within the mitochondrial organelle suggest that nuclei-encoded spliceosome can mediate splicing of mtRNA.
[Mh] Termos MeSH primário: Mitocôndrias/genética
RNA/genética
RNA/fisiologia
[Mh] Termos MeSH secundário: Núcleo Celular
Genoma
Humanos
Íntrons
Mitocôndrias/metabolismo
Processamento de RNA/fisiologia
Spliceossomos/genética
Spliceossomos/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, mitochondrial); 63231-63-0 (RNA)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1093/hmg/ddx142


  9 / 25087 MEDLINE  
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[PMID]:28383661
[Au] Autor:Zhang J; Khan A; Kennard A; Grigg ME; Parkinson J
[Ad] Endereço:Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
[Ti] Título:PopNet: A Markov Clustering Approach to Study Population Genetic Structure.
[So] Source:Mol Biol Evol;34(7):1799-1811, 2017 Jul 01.
[Is] ISSN:1537-1719
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:With the advent of low cost, high-throughput genome sequencing technology, population genomic data sets are being generated for hundreds of species of pathogenic, industrial, and agricultural importance. The challenge is how best to analyze and visually display these complex data sets to yield intuitive representations capable of capturing complex evolutionary relationships. Here we present PopNet, a novel computational method that identifies regions of shared ancestry in the chromosomes of related strains through clustering patterns of genetic variation. These relationships are subsequently visualized within a network by a novel implementation of chromosome painting. We apply PopNet to three diverse populations that feature differential rates of recombination and demonstrate its ability to capture evolutionary relationships as well as associate traits to specific loci. Compared with existing tools, PopNet provides substantial advances by both removing the need to predefine a single reference genome that can bias interpretation of population structure, as well as its ability to visualize multiple evolutionary relationships, such as recombination events and shared ancestry, across hundreds of strains.
[Mh] Termos MeSH primário: Genética Populacional/métodos
Genômica/métodos
Análise de Sequência de DNA/métodos
[Mh] Termos MeSH secundário: Algoritmos
Sequência de Bases
Mapeamento Cromossômico/métodos
Análise por Conglomerados
Variação Genética/genética
Genoma/genética
Desequilíbrio de Ligação/genética
Cadeias de Markov
Metagenômica/métodos
Polimorfismo de Nucleotídeo Único/genética
Recombinação Genética/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE
[do] DOI:10.1093/molbev/msx110


  10 / 25087 MEDLINE  
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[PMID]:28379581
[Au] Autor:Krasovec M; Eyre-Walker A; Sanchez-Ferandin S; Piganeau G
[Ad] Endereço:Sorbonne Universités, UPMC Univ Paris 06, CNRS, Biologie Intégrative des Organismes Marins (BIOM), Observatoire Océanologique, Banyuls/Mer, France.
[Ti] Título:Spontaneous Mutation Rate in the Smallest Photosynthetic Eukaryotes.
[So] Source:Mol Biol Evol;34(7):1770-1779, 2017 Jul 01.
[Is] ISSN:1537-1719
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mutation is the ultimate source of genetic variation, and knowledge of mutation rates is fundamental for our understanding of all evolutionary processes. High throughput sequencing of mutation accumulation lines has provided genome wide spontaneous mutation rates in a dozen model species, but estimates from nonmodel organisms from much of the diversity of life are very limited. Here, we report mutation rates in four haploid marine bacterial-sized photosynthetic eukaryotic algae; Bathycoccus prasinos, Ostreococcus tauri, Ostreococcus mediterraneus, and Micromonas pusilla. The spontaneous mutation rate between species varies from µ = 4.4 × 10-10 to 9.8 × 10-10 mutations per nucleotide per generation. Within genomes, there is a two-fold increase of the mutation rate in intergenic regions, consistent with an optimization of mismatch and transcription-coupled DNA repair in coding sequences. Additionally, we show that deviation from the equilibrium GC content increases the mutation rate by ∼2% to ∼12% because of a GC bias in coding sequences. More generally, the difference between the observed and equilibrium GC content of genomes explains some of the inter-specific variation in mutation rates.
[Mh] Termos MeSH primário: Clorófitas/genética
Fotossíntese/genética
[Mh] Termos MeSH secundário: Composição de Bases/genética
DNA Intergênico/genética
Eucariotos/genética
Evolução Molecular
Variação Genética
Genoma/genética
Mutação
Taxa de Mutação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Intergenic)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.1093/molbev/msx119



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