Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

Apolipoprotein D synthesis progressively increases in frontal cortex during human lifespan

Apolipoprotein D (apo D) is a lipocalin present in the nervous system that may be related to processes of reinnervation, regeneration and neuronal cell protection. In the other way, apo D expression has been correlated, in some brain regions, with normal aging and neurodegenerative diseases. To elucidate the regional and cellular expression of apo D in normal human brain during aging, we performed a detailed and extensive study in samples of post-mortem human cerebral cortices. To achieve this study, slot blot techniques, for protein and mRNA, as well as immunohistochemistry and hybridohistochemistry methods were used. A positive correlation for apo D expression with aging was found; furthermore, mRNA levels, as well as the protein ones, were higher in the white than in the grey matter. Immunohistochemistry and non-isotopic HIS showed that apo D is synthesized in both neurons and glial cells. Apo D expression is notorious in oligodendrocytes but with aging the number of neurons that synthesize apo D is increased. Our results indicate that apo D could play a fundamental role in central nervous system aging and in the reduction of products derivated from lipid peroxidation. The increment in the expression of apo D with aging can be included in a global mechanism of cellular protection to prevent the deleterious effects caused by aging

Ten-year trends in overweight and obesity in the adult Portuguese population, 1995 to 2005

There is little information regarding the trends in body mass index (BMI) and obesity in the overall Portuguese population, namely if these trends are similar according to educational level. In this study, we assessed the trends in the prevalence of overweight and obesity in the Portuguese population, overall and by educational level. Cross-sectional national health interview surveys conducted in 1995-6 (n = 38,504), 1998-9 (n = 38,688) and 2005-6 (n = 25,348). Data were derived from the population and housing census of 1991 and two geographically-based strata were defined. The sampling unit was the house, and all subjects living in the sampling unit were surveyed. Height and weight were self-reported; the effects of gender, age group and educational level were also assessed by self-reported structured questionnaires. Bivariate comparisons were performed using Chi-square or analysis of variance (ANOVA). Trends in BMI levels were assessed by linear regression analysis, while trends in the prevalence of obesity were assessed by logistic regression. Mean (±standard deviation) BMI increased from 25.2 ± 4.0 in 1995-6 to 25.7 ± 4.5 kg/m² in 2005-6. Prevalence of overweight remained stable (36.1% in 1995-6 and 36.4% in 2005) while prevalence of obesity increased (11.5% in 1995-6 and 15.1% in 2005-6). Similar findings were observed according to age group. Mean age-adjusted BMI increase (expressed in kg/m²/year and 95% confidence interval) was 0.073 (0.062, 0.084), 0.016 (0.000, 0.031) and 0.073 (0.049, 0.098) in men with primary, secondary and university levels, respectively; the corresponding values in women were 0.085 (0.073, 0.097), 0.052 (0.035, 0.069) and 0.062 (0.038, 0.084). Relative to 1995-6, obesity rates increased by 48%, 41% and 59% in men and by 40%, 75% and 177% in women with primary, secondary and university levels, respectively. The corresponding values for overweight were 6%, 1% and 23% in men and 5%, 7% and 65% in women. Between 1995 and 2005, obesity increased while overweight remained stable in the adult Portuguese population. Although higher rates were found among lesser educated subjects, the strong increase in BMI and obesity levels in highly educated subjects is of concern

The role of centrosomal Nlp in the control of mitotic progression and tumourigenesis

The human centrosomal ninein-like protein (Nlp) is a new member of the γ-tubulin complexes binding proteins (GTBPs) that is essential for proper execution of various mitotic events. The primary function of Nlp is to promote microtubule nucleation that contributes to centrosome maturation, spindle formation and chromosome segregation. Its subcellular localisation and protein stability are regulated by several crucial mitotic kinases, such as Plk1, Nek2, Cdc2 and Aurora B. Several lines of evidence have linked Nlp to human cancer. Deregulation of Nlp in cell models results in aberrant spindle, chromosomal missegregation and multinulei, and induces chromosomal instability and renders cells tumourigenic. Overexpression of Nlp induces anchorage-independent growth and immortalised primary cell transformation. In addition, we first demonstrate that the expression of Nlp is elevated primarily due to NLP gene amplification in human breast cancer and lung carcinoma. Consistently, transgenic mice overexpressing Nlp display spontaneous tumours in breast, ovary and testicle, and show rapid onset of radiation-induced lymphoma, indicating that Nlp is involved in tumourigenesis. This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis