Assuntos
Cardiomiopatia Restritiva/etiologia , Fibrose Endomiocárdica/complicações , Eosinofilia/complicações , Miocárdio/patologia , Biópsia , Cardiomiopatia Restritiva/diagnóstico , Diagnóstico Diferencial , Ecocardiografia , Fibrose Endomiocárdica/diagnóstico , Eosinofilia/diagnóstico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
RNA editing by adenosine deamination, catalyzed by adenosine deaminases acting on RNA (ADAR), is a post-transcriptional modification that contributes to transcriptome and proteome diversity and is widespread in mammals. Here we administer a bioinformatics search strategy to the human and mouse genomes to explore the landscape of A-to-I RNA editing. In both organisms we find evidence for high excess of A/G-type discrepancies (inosine appears as a guanosine in cloned cDNA) at non-polymorphic, non-synonymous codon sites over other types of discrepancies, suggesting the existence of several thousand recoding editing sites in the human and mouse genomes. We experimentally validate recoding-type A-to-I RNA editing in a number of human genes with high scoring positions including the coatomer protein complex subunit alpha (COPA) as well as cyclin dependent kinase CDK13.
Assuntos
Adenina/metabolismo , Edição de RNA/genética , Animais , Sequência de Bases , Genoma Humano , Genômica , Humanos , Inosina/metabolismo , Camundongos , TranscriptomaAssuntos
Insuficiência da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Bioprótese/efeitos adversos , Próteses Valvulares Cardíacas/efeitos adversos , Falha de Prótese , Idoso de 80 Anos ou mais , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos , ReoperaçãoRESUMO
To investigate the voltage dependence of the Na+/K+ pump, current-voltage relations were determined in prophase-arrested oocytes of Xenopus laevis. All solutions contained 5 mM Ba2+ and 20 mM tetraethylammonium (TEA) to block K+ channels. If, in addition, the Na+/K+ pump is blocked by ouabain, K(+)-sensitive currents no larger than 50 nA/cm2 remain. Reductions in steady-state current (on the order of 700 nA/cm2) produced by 50 microM ouabain or dihydro-ouabain or by K+ removal, therefore, primarily represent current generated by the Na+/K+ pump. In Na(+)-free solution containing 5 mM K+, Na+/K+ pump current is relatively voltage independent over the potential range from -160 to +40 mV. If external [K+] is reduced below 0.5 mM, negative slopes are observed over this entire voltage range. Similar results are seen in Na(+)- and Ca(2+)-free solutions in the presence of 2 mM Ni2+, an experimental condition designed to prevent Na+/Ca2+ exchange. The occurrence of a negative slope can be explained by the voltage dependence of the apparent affinity for activation of the Na+/K+ pump by external K+, consistent with the existence of an external ion well for K+ binding. In 90 mM Na+, 5 mM K+ solution, Na+/K+ pump current-voltage curves at negative membrane potentials have a positive slope and can be described by a monotonically increasing sigmoidal function. At an extracellular [K+] of 1.3 mM, a negative slope was observed at positive potentials. These findings suggest that in addition to a voltage-dependent step associated with Na+ translocation, a second voltage-dependent step that is dependent on external [K+], possibly external K+ binding, participates in the overall reaction mechanism of the Na+/K+ pump.