Biomedical subjects

Miguel R Branco

Publications and source records attributed to Miguel R Branco.

5 recordsLinked to original sources

PubMed2007

Chromosome organization: new facts, new models.

The study of nuclear organization has radically changed the way we envision gene regulation, imposing a paradigm shift from a seemingly featureless nucleus to a highly compartmentalized and complex organelle. The positioning of genes, regulatory sequences and transcription factors in relation to each other and to landmarks in the nucleus, such as nuclear bodies and the lamina, is important in determining which genes are transcribed at any one time. Investigating chromatin organization during interphase is therefore essential to the understanding of gene expression. The recent discovery of interactions between distal chromatin segments that occur within the same chromosome or across different chromosomes, and that have a role in transcription regulation, suggests a re-evaluation of current models of chromosome organization and the development of new ones.

Animals↗

PubMed2006

Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations.

After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability.

Cells, Cultured↗

PubMed2005

[Hypercalcemic crisis associated with primary hyperparathyroidism during pregnancy].

Primary hyperparathyroidism is a rare occurrence in pregnancy with significant risks to the mother and the foetus, witch is related to the level of serum calcium. A 41-year-old women, gravida 2, para 1, presented at 22 weeks gestation with nausea, vomiting and mild cognitive dysfunction associated with hypercalcemic crisis. The hypercalcemia was observed to be related to parathyroid hyperplasia that was surgically removed. Complete resolution of her symptomatology and hypercalcemia occurred postoperatively. The pregnancy was complicated with transient hypertension. A small for gestational age healthy male infant was delivered at term with no neonatal complications related with this pathology.

Adenoma↗

PubMed2005

[Multiple gestation epidemiology--15 years survey].

Between January of 1987 and December of 2001 were born 1243 twins related to 609 multiple pregnancies, in Maternidade Bissaya-Barreto. Data were grouped in periods of three years and several parameters were studied. The rate of multiple gestation has increased probably due to the contribution of the assisted conception techniques, and to the increase of the number of multiple fetal pregnancies (two or more) and to the increase of the mother age. These more frequent obstetric problems were preterm birth, gestational hypertension and abnormal sonographic data of fetal growth. The average age of delivery was 34 weeks and the birth weight has decreased. The most important factors for neonatal morbidity were hyaline membranous disease, intraventricular haemorrhage and the twin-twin transfusion syndrome. The neonatal mortality decreased in the last studied period.

Adult↗

PubMed2003

Decrease of H2O2 plasma membrane permeability during adaptation to H2O2 in Saccharomyces cerevisiae.

Contrary to what is widely believed, recent published results show that H2O2 does not freely diffuse across biomembranes. The fast removal of H2O2 by antioxidant enzymes is able to generate a gradient if H2O2 is produced in a different compartment from that containing the enzymes (Antunes, F., and Cadenas, E. (2000) FEBS Lett. 475, 121-126). In this work, we extended these studies and tested whether an active regulation of biomembranes permeability characteristics is part of the cell response to oxidative stress. Using Saccharomyces cerevisiae as a model, we showed that: (a) H2O2 gradients across the plasma membrane are formed upon exposure to external H2O2; (b) there is a correlation between the magnitude of the gradients and the resistance to H2O2; (c) there is not a correlation between the intracellular capacity to remove H2O2 and the resistance to H2O2; (d) the plasma membrane permeability to H2O2 decreases by a factor of two upon acquisition of resistance to this agent by pre-exposing cells either to nonlethal doses of H2O2 or to cycloheximide, an inhibitor of protein synthesis; and (e) erg3Delta and erg6Delta mutants, which have impaired ergosterol biosynthesis pathways, show higher plasma membrane permeability to H2O2 and are more sensitive to H2O2. Altogether, the regulation of the plasma membrane permeability to H2O2 emerged as a new mechanism by which cells respond and adapt to H2O2. The consequences of the results to cellular redox compartmentalization and to the origin and evolution of the eukaryotic cell are discussed.

Antioxidants↗