PubMed Health⌕ Search

Biomedical subjects

M T Teixeira

Publications and source records attributed to M T Teixeira.

4 recordsLinked to original sources

Telomere maintenance, function and evolution: the yeast paradigm.

Telomeres are multifunctional genetic elements that cap chromosome ends, playing essential roles in genome stability, chromosome higher-order organization and proliferation control. The telomere field has largely benefited from the study of unicellular eukaryotic organisms such as yeasts. Easy cultivation in laboratory conditions and powerful genetics have placed mainly Saccharomyces cerevisiae, Kluveromyces lactis and Schizosaccharomyces pombe as crucial model organisms for telomere biology research. Studies in these species have made it possible to elucidate the basic mechanisms of telomere maintenance, function and evolution. Moreover, comparative genomic analyses show that telomeres have evolved rapidly among yeast species and functional plasticity emerges as one of the driving forces of this evolution. This provides a precious opportunity to further our understanding of telomere biology.

Ascomycota↗

Self-catalyzed cleavage of the yeast nucleoporin Nup145p precursor.

Nup145p is a component of the nuclear pore complex of Saccharomyces cerevisiae and is essential for mRNA export. Nup145p and its apparent vertebrate homologue are the only known nucleoporins to be composed of two functionally independent peptide moieties resulting from the post-translational cleavage of a large precursor molecule. In this study, the proteolytic cleavage site of Nup145p has been mapped upstream of an evolutionary conserved serine residue. Cleavage occurs at the same site when a precursor is artificially expressed in Escherichia coli. A hydroxyl-containing residue is critical for the reaction, although a thiol-containing residue offers an acceptable replacement. In vitro kinetics experiments using a purified precursor molecule demonstrate that the cleavage is self-catalyzed and that the catalytic domain lies within the N-terminal moiety. Taken altogether, our data are consistent with a proteolytic mechanism involving an N>O acyl rearrangement and a subsequent ester intermediate uncovered in other self-processing proteins.

Catalysis↗

Two functionally distinct domains generated by in vivo cleavage of Nup145p: a novel biogenesis pathway for nucleoporins.

Nup145p is an essential yeast nucleoporin involved in nuclear export of polyadenylated RNAs. We demonstrate here that Nup145p is cleaved in vivo to yield two functionally distinct domains: a carboxy-terminal domain (C-Nup145p) which is located at the nuclear pore complex (NPC) and assembles into the Nup84p complex, and a GLFG-containing amino-terminal domain (N-Nup145p) which is not part of this complex. Whereas the essential C-Nup145p accomplishes the functions required for efficient mRNA export and normal NPC distribution, N-Nup145p, which is homologous to the GLFG-containing nucleoporins Nup100p and Nup116p, is not necessary for cell growth. However, the N-Nup145p becomes essential in a nup188 mutant background. Strikingly, generation of a free N-domain is a prerequisite for complementation of this peculiar synthetic lethal mutant. These data suggest that N- and C-domains of Nup145p perform independent functions, and that the in vivo cleavage observed is of functional importance.

Amino Acid Sequence↗

[Non-communicable chronic diseases in Brazil: from risk factors to social impact].

The current epidemiologic profile of Brazil includes both the diseases of underdevelopment and those associated with modern life. Consequently, the country faces the difficult task of carrying out health promotion and protection activities aimed at controlling communicable diseases as well as noncommunicable chronic diseases (NCDs). This study sought to describe the epidemiologic situation of Brazilian adults with regard to NCDs and to present available data on the quality of care provided for these diseases and their social impact. To these ends, a literature review was conducted for the period 1964-1995--that is, since the beginning of the production and dissemination of data on cardiovascular diseases, cancer, and diabetes. Of the 153 bibliographic references that were discovered, 97 were used. The social, political, economic, and health inequities that exist among Brazil's geographic regions are reflected in the national scientific production, which is concentrated in the Southeast and South. Most of the studies based on primary data come from those regions. Information is scarce from the North-east, except the city of Salvador. Therefore, the health profile of adults--including risk factors and morbidity and mortality--can be better delineated for residents of the South and Southeast of the country, whereas for the other regions the necessary information is practically nonexistent. Risk factors linked to life-style are as widespread and important in Brazil as they are in industrialized countries. Prevalence and mortality rates among persons with or without certain socio-environmental risks (such as low level of schooling or unskilled occupations) indicate that NCDs predominate in the lowest social strata. Inter-regional differences in the prevalence of arterial hypertension and diabetes mellitus, the most common fatal cardiovascular causes, and the predominant cancers, as well as morbidity and mortality in both sexes, illustrate the political, social, and economic inequities of development in each region. Comparisons with other countries of the incidence of cardiovascular diseases in a capital in the Northeast or mortality from cardiovascular diseases in the capitals in the South and Southeast show, in the first case, that Salvador has the highest incidence among the Western countries analyzed and, in the second case, that the mortality data rank among the top seven. Cardiovascular diseases and diabetes show increasing trends, with the exception of a small decline for ischemic heart disease and cerebrovascular disease in the municipality of São Paulo. Deaths rates in hospitals from specific cardiovascular diseases and avoidable complications of diabetes are high, especially among indigent patients as opposed to private patients. Premature mortality, as measured by productive years of life lost, reflects the poor quality of medical care and the absence of targeted control programs. These data, combined with other sources of information, such as consents for treatment and pensions paid for illness, give some idea of the impact of NCDs on the society. The authors point to the basic research that could be done in all the country's regions to serve as a basis for planning and implementing populational strategies to reduce risk factors and to treat and control chronic noncommunicable diseases in Brazil.

Adolescent↗