Reproducibility of biomedical research: Quo vadis?

This is the peer reviewed version of the following article: Medicina Clínica 146.9 (2016): 408-412, which has been published in final form at http://dx.doi.org/10.1016/j.medcli.2015.11.02

Mitochondrial tRNA Valine in Cardiomyopathies

Mitochondrial respiratory chain disorders are a heterogeneous group of diseases that clinically involve multiple tissues although they tend to mainly affect nervous system and skeletal muscle. The predominance of neurologic and neuromuscular manifestations in mitochondrial diseases has generally masked the presence of other, but not less important, clinical phenotypes, such as cardiac complications. Nowadays, mitochondrial defects are being increasingly recognized to play an important role in the pathogenesis of a subgroup of cardiomyopathies produced by defects in the energetic metabolism (mitochondrial cardiomyopathies). These diseases can result from mutations in either nuclear or mitochondrial encoded genes although mitochondrial DNA mutations are more frequent. In fact, cardiac conduction abnormalities have been associated with different mtDNA rearrangements. In a same way, sporadic or inherited mutations in mitochondrial DNA specifically in the mitochondrial transfer ribonucleic acid genes (mostly in the tRNALeu(UUR) and tRNAIle) have also been associated with hypertrophic and dilated cardiomyopathy. Mitochondrial diseases caused by mutations in the mitochondrial tRNAVal gene (MT-TV) are not very frequent. However, a relatively high percentage of mutations in this gene have been associated with mitochondrial cardiomyopathy. Besides, functional and molecular analyses suggest that the MT-TV gene should be routinely considered in the diagnosis when there is a high suspicion of mitochondrial cardiomyopathy. Finally, the increasingly importance of the role that this gene has begun to play in the pathophysiology of mitochondrial cardiomyopathies indicates that future studies about the molecular mechanisms that could explain why the cardiomyopathy phenotype appears must be carried ouThis work was supported by grants of the Center for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (grants PI 07/0167, PI 10/0703 to R.G. and PI06/0205, PS09/00941 to B.B.) and Comunidad de Madrid (grant number S2010/BMD-2402)

Aprendiendo química en casa

Es posible demostrar que la Química no es algo misterioso, ni limitado a los laboratorios de investigación, realizando experimentos fuera del colegio o en nuestra casa, y observando cómo y por qué tienen lugar ciertas reacciones químicas que se producen diariamente a nuestro alrededor. Para ello, se pueden utilizar los materiales y las sustancias de la cocina como si de un pequeño laboratorio de química se tratara. Se aprenden así diferentes contenidos, mediante una enseñanza activa que pretende atender a la diversidad del alumnado según sus intereses y capacidades.Palabras clave: experiencias de química, materiales caseros, atención a la diversidad

Aprendiendo química en casa

Es posible demostrar que la Química no es algo misterioso, ni limitado a los laboratorios de investigación, realizando experimentos fuera del colegio o en nuestra casa, y observando cómo y por qué tienen lugar ciertas reacciones químicas que se producen diariamente a nuestro alrededor. Para ello, se pueden utilizar los materiales y las sustancias de la cocina como si de un pequeño laboratorio de química se tratara. Se aprenden así diferentes contenidos, mediante una enseñanza activa que pretende atender a la diversidad del alumnado según sus intereses y capacidades

The Drosophila nuclear factor DREF positively regulates the expression of the mitochondrial transcription termination factor DmTTF

et al.The DREF [DRE (DNA replication-related element)-binding factor], which regulates the transcription of a group of cell proliferation-related genes in Drosophila, also controls the expression of three genes involved in mtDNA (mitochondrial DNA) replication and maintenance. In the present study, by in silico analysis, we have identified DREs in the promoter region of a gene participating in mtDNA transcription, the DmTTF (Drosophila mitochondrial transcription termination factor). Transient transfection assays in Drosophila S2 cells, with mutated versions of DmTTF promoter region, showed that DREs control DmTTF transcription; moreover, gel-shift and Chip (chromatin immunoprecipitation) assays demonstrated that the analysed DRE sites interact with DREF in vitro and in vivo. Accordingly, DREF knock-down in S2 cells by RNAi (RNA interference) induced it considerable decrease in DmTTF mRNA level. These results clearly demonstrate that DREF positively controls DmTTF expression. On the other hand, mtRNApol (mitochondrial RNA polymerase) lacks DREs in its promoter and is not regulated in vivo by DREF. In situ RNA hybridization Studies showed that DmTTF was transcribed almost ubiquitously throughout all stages of Drosophila embryogenesis, whereas mRNApol was efficiently transcribed from stages 11-12. Territories where transcription occurred mostly were the gut and Malpighi tubes for DmTTF, and the gut, mesoderm, pharyngeal muscle and Malpighi tubes for mtRNApol. The partial overlapping in the temporal and spatial mRNA expression patterns confirms that transcription of the two genes is differentially regulated during embryogenesis and suggests that DmTTF might play multiple roles in the mtDNA transcription process, for which different levels of the protein with respect to mtRNApol are required.Peer reviewe