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1.
Proc Biol Sci ; 283(1823)2016 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-26817772

RESUMEN

Assembling the global eukaryotic tree of life has long been a major effort of Biology. In recent years, pushed by the new availability of genome-scale data for microbial eukaryotes, it has become possible to revisit many evolutionary enigmas. However, some of the most ancient nodes, which are essential for inferring a stable tree, have remained highly controversial. Among other reasons, the lack of adequate genomic datasets for key taxa has prevented the robust reconstruction of early diversification events. In this context, the centrohelid heliozoans are particularly relevant for reconstructing the tree of eukaryotes because they represent one of the last substantial groups that was missing large and diverse genomic data. Here, we filled this gap by sequencing high-quality transcriptomes for four centrohelid lineages, each corresponding to a different family. Combining these new data with a broad eukaryotic sampling, we produced a gene-rich taxon-rich phylogenomic dataset that enabled us to refine the structure of the tree. Specifically, we show that (i) centrohelids relate to haptophytes, confirming Haptista; (ii) Haptista relates to SAR; (iii) Cryptista share strong affinity with Archaeplastida; and (iv) Haptista + SAR is sister to Cryptista + Archaeplastida. The implications of this topology are discussed in the broader context of plastid evolution.


Asunto(s)
Evolución Biológica , Eucariontes/genética , Variación Genética , Genómica , Filogenia , Eucariontes/clasificación
2.
J Immunol ; 190(8): 3949-58, 2013 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-23487427

RESUMEN

Respiratory diseases are the most frequent chronic illnesses in babies and children. Although a vigorous innate immune system is critical for maintaining lung health, a balanced response is essential to minimize damaging inflammation. We investigated the functional and clinical impact of human genetic variants in the promoter of NFKBIA, which encodes IκBα, the major negative regulator of NF-κB. In this study, we quantified the functional impact of NFKBIA promoter polymorphisms (rs3138053, rs2233406, and rs2233409) on promoter-driven protein expression, allele-specific and total NFKBIA mRNA expression, IκBα protein expression, and TLR responsiveness; mapped innate immune regulatory networks active during respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia; and genotyped and analyzed independent cohorts of children with respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Genetic variants in the promoter of NFKBIA influenced NFKBIA gene expression, IκBα protein expression, and TLR-mediated inflammatory responses. Using a systems biology approach, we demonstrated that NFKBIA/IκBα is a central hub in transcriptional responses of prevalent childhood lung diseases, including respiratory syncytial virus infection, asthma, and bronchopulmonary dysplasia. Finally, by examining independent pediatric lung disease cohorts, we established that this immunologically relevant genetic variation in the promoter of NFKBIA is associated with differential susceptibility to severe bronchiolitis following infection with respiratory syncytial virus, airway hyperresponsiveness, and severe bronchopulmonary dysplasia. These data highlight the importance of negative innate immune regulators, such as NFKBIA, in pediatric lung disease and begin to unravel common aspects in the genetic predisposition to bronchopulmonary dysplasia, bronchiolitis, and childhood asthma.


Asunto(s)
Asma/inmunología , Bronquiolitis/inmunología , Displasia Broncopulmonar/inmunología , Predisposición Genética a la Enfermedad , Variación Genética/inmunología , Subunidad p50 de NF-kappa B/genética , Animales , Asma/genética , Bronquiolitis/genética , Bronquiolitis/virología , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/virología , Células CHO , Niño , Preescolar , Cricetinae , Femenino , Humanos , Lactante , Recién Nacido , Subunidad p50 de NF-kappa B/fisiología , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Virus Sincitiales Respiratorios/inmunología
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