Trypanosoma cruzi infection is a major cause of cardiomyopathy. Previous gene profiling studies of infected mouse hearts have revealed prominent changes in gene expression within many functional pathways. This variety of transcriptomic changes in infected mice raises the question of whether gene expression alterations in whole hearts are due to changes in infected cardiac myocytes or other cells or even to systemic effects of the infection on the heart. We employed microarrays to examine infected cardiac myocyte cultures 48 h post-infection. Statistical comparison of gene expression levels of 7624 well annotated unigenes in four independent cultures of infected and uninfected myocytes detected substantial (≥1.5 absolute fold changes) in 420 (5.5%) of the sampled genes. Major categories of affected genes included those involved in immune response, extracellular matrix and cell adhesion. These findings on infected cardiac myocytes in culture reveal that alterations in cardiac gene expression described in Chagas disease are the consequence of both direct infection of the myocytes themselves as well as resulting from the presence of other cell types in the myocardium and systemic effects of infection.
Although bone marrow-derived mononuclear cells (BMNC) have been extensively used in cell therapy for cardiac diseases, little mechanistic information is available to support reports of their efficacy. To address this shortcoming, we compared structural and functional recovery and associated global gene expression profiles in post-ischaemic myocardium treated with BMNC transplantation. BMNC suspensions were injected into cardiac scar tissue 10 days after experimental myocardial infarction. Six weeks later, mice undergoing BMNC therapy were found to have normalized antibody repertoire and improved cardiac performance measured by ECG, treadmill exercise time and echocardiography. After functional testing, gene expression profiles in cardiac tissue were evaluated using high-density oligonucleotide arrays. Expression of more than 18% of the 11981 quantified unigenes was significantly altered in the infarcted hearts. BMNC therapy restored expression of 2099 (96.2%) of the genes that were altered by infarction but led to altered expression of 286 other genes, considered to be a side effect of the treatment. Transcriptional therapeutic efficacy, a metric calculated using a formula that incorporates both recovery and side effect of treatment, was 73%. In conclusion, our results confirm a beneficial role for bone marrow-derived cell therapy and provide new information on molecular mechanisms operating after BMNC transplantation on post ischemic heart failure in mice.
Resumo: Embora sejam temas de relevância para o pensamento linguístico moderno, o uso, a variação e a norma da linguagem foram também abordados por autores latinos no âmbito dos discursos retórico e gramatical. Considerando, sobretudo, a obra de Quintiliano (séc. I d.C.) e os tratados gramaticais de Donato e Diomedes (séc. IV d.C.), este artigo tem por meta oferecer uma apresentação de como estes conceitos se afiguravam no discurso metalinguístico antigo, atrelados à noção de Latinitas, que codificava a norma social e linguística para o uso linguístico, separando a linguagem do romano culto -adequada à produção de textos oratórios -da linguagem eivada de elementos bárbaros -inadequada em determinados contextos. A noção de Latinitas emergia, assim, de uma reflexão antiga que considerou as variações da língua segundo diferentes usos e estipulou certa norma que era contextualmente dependente. Palavras-chave: Variação. Norma. Latinitas. Tradição gramatical latina.Abstract: Despite being relevant themes for the modern linguistic thought, the language use, variation and norm have been also addressed by Latin authors under the scope of the rhetoric and grammatical discourses. By considering the work of Quintilian (c. I a.D.) and the grammatical treatises by Donat and Diomedes (c. IV a.D.), this article aims at offering a presentation of how such concepts figured in the ancient metalinguistic discourse, associated to the notion of Latinitas, which codified the social and linguistic norm for the language use, setting apart the schooled Roman languageadequate to the production of oratory texts -from the language full of
A aposição de elementos gregos e latinos engendra, no De constructione, frequentes comparações e contrastes entre os dois sistemas linguísticos, procedimento que representa um artifício de explicação gramatical amplamente utilizado pelo gramático latino. Neste artigo, examinamos dois tipos de comparações que podemos observar nessa obra: aquelas do tipo “inventário”, que se verificam pela mera justaposição de vocábulos, expressões ou sentenças de ambas as línguas, com o objetivo de ilustrar semelhanças entre aspectos gramaticais do grego e do latim, e aquelas que compreendem “análises translinguísticas”, que pretendem explicar diferenças gramaticais entre o latim e o grego. Pretendemos mostrar que, através dessas comparações e contrastes, Prisciano elabora um discurso teórico que resulta da síntese entre as duas línguas, cujo propósito – a ser melhor investigado –, parece ser o de produzir uma aproximação simbólica do oriente (grego) ao ocidente (latino).
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