Guerrero L.,Instituto Investigaciones Biomedicas |
Marco-Ferreres R.,Instituto Investigaciones Biomedicas |
Serrano A.L.,University Pompeu Fabra |
Arredondo J.J.,Instituto Investigaciones Biomedicas |
Cervera M.,Instituto Investigaciones Biomedicas
Developmental Biology | Year: 2010
Although tight quantitative control of gene expression is required to ensure that organs and tissues function correctly, the transcriptional mechanisms underlying this process still remain poorly understood. Here, we describe novel and evolutionary conserved secondary enhancers that are needed for the regulation of the expression of Troponin I genes. Secondary enhancers are silent when tested individually in electroporated muscles but interact with the primary enhancers and are required to precisely control the appropriate timing, the tissue and fibre specificity, and the quantitative expression of these genes during muscle differentiation. Synergism is completely dependent of the fully conserved MEF2 site present on the primary enhancers core of skeletal muscle Troponin I genes. Thus, while each of these paired enhancers has a different function, the concerted action of both is crucial to recapitulate endogenous gene expression. Through comparative genomics, we predict that this mechanism has also arisen in other mammalian muscle genes. Our results reveal the existence of a novel mechanism, conserved from flies to mammals, to fine-tune gene expression in each muscle and probably other tissues. © 2009 Elsevier Inc. All rights reserved.
Ibarra-Gonzalez I.,Instituto Investigaciones Biomedicas |
Fernandez-Lainez C.,Instituto Investigaciones Biomedicas |
Vela-Amieva M.,Instituto Investigaciones Biomedicas
Clinical Biochemistry | Year: 2010
Objectives: To report the clinical and laboratory characteristics of urea cycle disorder (UCD) patients at a tertiary care center in a developing country. Design and methods: Retrospective study of clinical and laboratory data of UCD patients. Results: Thirty-seven UCD patients were studied, 31 symptomatic (high risk) patients (15 neonatal onset, 16 late onset) and 6 with positive neonatal screening. Argininosuccinate synthetase deficiency was the most frequent disease (17/37, 46%), followed by ornithine transcarbamylase (10/37, 27%), arginase (7/37, 19%), and argininosuccinate lyase (3/37, 8%) deficiencies. Mortality of symptomatic patients was 38% (10/26), neonatal onset had the worst outcome, with 50% of survival. Conclusions: In Mexico, the mortality of the UCD patients is higher than those reported in other countries, and neurological sequels are frequent and severe. It is essential to implement practice guidelines for the professional management of these patients. © 2009 The Canadian Society of Clinical Chemists.