Differential expression of GSPT1 GGCn alleles in cancer

The human eukaryotic release factor 3a (eRF3a), encoded by the G1 to S phase transition 1 gene (GSPT1; alias eRF3a), is upregulated in various human cancers. GSPT1 contains a GGCn polymorphism in exon 1, encoding a polyglycine expansion in the N-terminal of the protein. The longer allele, GGC12, was previously shown to be associated to cancer. The GGC12 allele was present in 2.2% of colorectal cancer patients but was absent in Crohn disease patients and in the control group. Real-time quantitative RT-PCR analysis showed that the GGC12 allele was present at up to 10-fold higher transcription levels than the GGC10 allele (P < 0.001). No GSPT1 amplifications were detected, and there was no correlation between the length of the alleles and methylation levels of the CpG sites inside the GGC expansion. Using flow cytometry, we compared the levels of apoptosis and proliferation rates between cell lines with different genotypes, but detected no significant differences. Finally, we used a cytokinesis-block micronucleus assay to evaluate the frequency of micronuclei in the same cell lines. Cell lines with the longer alleles had higher frequencies of micronuclei in binucleated cells, which is probably a result of defects in mitotic spindle formation. Altogether, these findings indicate that GSPT1 should be considered a potential proto-oncogene.

eRF3a/GSPT1 12-GGC allele increases the susceptibility for breast cancer development

It is now widely recognized that translation factors are involved in cancer development and that components of the translation machinery that are deregulated in cancer cells may become targets for cancer therapy. The eukaryotic Release Factor 3 (eRF3) is a GTPase that associates with eRF1 in a complex that mediates translation termination. eRF3a/GSPT1 first exon contains a (GGC)n expansion coding for proteins with different N-terminal extremities. Herein we show that the longer allele (12-GGC) is present in 5.1% (7/137) of the breast cancer patients analysed and is absent in the control population (0/135), corresponding to an increased risk for cancer development, as revealed by Odds Ratio analysis. mRNA quantification suggests that patients with the 12-GGC allele overexpress eRF3a/GSPT1 in tumor tissues relative to the normal adjacent tissues. However, using an in vivo assay for translation termination in HEK293 cells, we do not detect any difference in the activity of the eRF3a proteins encoded by the various eRF3a/GSPT1 alleles. Although the connection between the presence of eRF3a/GSPT1 12-GGC allele and tumorigenesis is still unknown, our data suggest that the presence of the 12-GGC allele provides a potential novel risk marker for various types of cancer.

5' and 3' UTR thymidylate synthase polymorphisms modulate the risk of colorectal cancer independently of the intake of methyl group donors

Thymidylate synthase, as a rate-limiting step in DNA synthesis, catalyses the conversion of dUMP into dTMP using 5,10-methylenotetrahydrofolate as the methyl donor. Two polymorphisms have been described in this gene: a repeat polymorphism in the 5' promoter enhancer region (3R versus 2R) and a 6 bp deletion in the 3' unstranslated region. Both of these may affect protein levels. The present case control study was aimed at investigating the influence of these two polymorphisms on the development of colorectal cancer (CRC), as well as their potential interaction with folate, vitamin B6 and vitamin B12 intake. A total of 196 cases and 200 controls, matched for age and sex distribution, were included in the study. No association was found between CRC and the 28 bp repeat polymorphism, but it was observed that individuals with the 6 bp/del and del/del genotypes had a significantly lower risk of developing the disease (OR=0.47; 95% CI 0.30-0.72). A combined genotype (2R/2R; 6 bp/del+del/del) was also found, which was associated with an even lower risk of developing of the disease (OR=0.42; 95% CI 0.26-0.69). No significant interaction between these polymorphisms and vitamin intake was observed. These results indicate for the first time that the 6 bp/del allele might be a protective factor in the development of CRC, independent of the intake of methyl group donors.

The D1822V APC polymorphism interacts with fat, calcium, and fiber intakes in modulating the risk of colorectal cancer in Portuguese persons

Background - Both genetic and environmental factors affect the risk of colorectal cancer (CRC). Objective - We aimed to examine the interaction between the D1822V polymorphism of the APC gene and dietary intake in persons with CRC. Design - Persons with CRC (n = 196) and 200 healthy volunteers, matched for age and sex in a case-control study, were evaluated with respect to nutritional status and lifestyle factors and for the D1822V polymorphism. Results - No significant differences were observed in energy and macronutrient intakes. Cases had significantly (P < 0.05) lower intakes of carotenes, vitamins C and E, folate, and calcium than did controls. Fiber intake was significantly (P = 0.004) lower in cases than in controls, whereas alcohol consumption was associated with a 2-fold risk of CRC. In addition, cases were significantly (P = 0.001) more likely than were controls to be sedentary. The homozygous variant for the APC gene (VV) was found in 4.6% of cases and in 3.5% of controls. Examination of the potential interactions between diet and genotype found that a high cholesterol intake was associated with a greater risk of colorectal cancer only in noncarriers (DD) of the D1822V APC allele (odds ratio: 1.66; 95% CI: 1.00, 2.76). In contrast, high fiber and calcium intakes were more markedly associated with a lower risk of CRC in patients carrying the polymorphic allele (DV/VV) (odds ratio: 0.50; 95% CI: 0.27, 0.94 for fiber; odds ratio: 0.51; 95% CI: 0.28, 0.93 for calcium) than in those without that allele. Conclusion - These results suggest a significant interaction between the D1822V polymorphism and the dietary intakes of cholesterol, calcium, and fiber for CRC risk.

Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells

The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition caused by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells.

Aspectos da mortalidade atribuível ao tabaco: revisão sistemática

O artigo teve por objetivo analisar as metodologias publicadas e empregadas no cálculo da mortalidade atribuível ao fumo. Foram pesquisadas as bases de dados eletrônicas MEDLINE, LILACS entre 1990 e 2006. Foram encontrados 186 estudos que apresentaram a mensuração de mortalidade a partir do cálculo da fração atribuível ao fumo. Desses, foram selecionados 41 artigos. Os estudos realizados nos Estados Unidos e Canadá apresentaram metodologia uniformizada e taxas de mortalidade entre 18%-23%; 25%-29% no sexo masculino e 14%-17% no feminino. As variações metodológicas podem justificar as diferenças da mortalidade entre os estudos e nas estimativas para as principais doenças tabaco-relacionadas.

Oral health, hygiene practices and oral cancer

OBJECTIVE: To assess the association between oral health and hygiene practices and oral cancer. METHODS: Hospital-based case-control study in the metropolitan area of São Paulo, southeastern Brazil, from 1998 to 2002. A total 309 patients with squamous cell carcinoma of the mouth and the pharynx and 468 controls matched by sex and age were included in the study. Cases were recruited in seven reference hospitals and controls were selected in five out of the seven participating hospitals. Detailed information on smoking, alcohol consumption, schooling, oral health status and hygiene practices were obtained through interviews. Odds ratios (OR) and 95% confidence intervals (95% CI), adjusted by sex, age, schooling, smoking, alcohol consumption as well as the variables oral health status and hygiene practices were estimated using unconditional logistic regression analyses. RESULTS: The use of complete dental prosthesis was not associated with oral cancer but regular gum bleeding showed a strong association (OR 3.1; 95% CI 1.2-7.9). Those who never attended a dental visit were more likely to have oral cancer (OR 2.5; 95% CI 1.3-4.8). Daily mouthwash use showed a stronger association to pharynx (OR 4.7; 95% CI 1.8-12.5) than mouth cancer (OR 3.2; 95% CI 1.6-6.3). CONCLUSIONS: Gum bleeding, no dental care, and daily mouthwash use were factors associated with oral cancer regardless of tobacco and alcohol consumption.

Aspectos da validação de escalas de avaliação do funcionamento do aluno

Neste trabalho são apresentados resultados decorrentes do processo de validação de duas Escalas de avaliação do funcionamento do aluno do ensino básico. Trata-se de Escalas de auto-relato, para uso do professor. Ambas as Escalas são definidas por diferentes dimensões que, no seu conjunto, procuram dar informação sobre o modo como o aluno explora os conteúdos programáticos, organiza o trabalho escolar e se relaciona com os outros, em especial com os pares. Os resultados que se apresentam procuram traduzir a consistência interna de cada uma das dimensões, assim como o comportamento de variáveis sociodemográficas e escolares por dimensão.

Factors related to inadequate cervical cancer screening in two Brazilian state capitals

OBJECTIVE:To analyze factors associated with cervical cancer screening failure. METHODS:Population-based cross-sectional study with self-weighted two-stage cluster sampling conducted in the cities of Fortaleza (Northeastern Brazil) and Rio de Janeiro (Southeastern Brazil) in 2002. Subjects were women aged 25-59 years in the last three years prior to the study. Data were analyzed through Poisson regression using a hierarchical model. RESULTS: The proportion of women who did not undergo the Pap smear test in Fortaleza and Rio de Janeiro was 19.1% (95% CI: 16.1;22.1) and 16.5% (95% CI: 14.1;18.9), respectively. Higher prevalence ratios of cervical cancer screening failure in both cities were seen among women with low education and low per capita income, old age, unmarried, who never underwent mammography, clinical breast examination, and blood glucose and cholesterol level testing. Smokers also had lower screening rates compared to non-smoker women and this difference was only statistically significant in Rio de Janeiro. CONCLUSIONS:The study findings point to the need of intervention focusing particularly women in worse socioeconomic conditions and access to healthcare, old-aged and unmarried. Education activities must prioritize screening of asymptomatic women and early diagnosis for symptomatic women and access to adequate diagnostic methods and treatment should be provided.

Aspectos de aprendizagem em optimização

A optimização e a aprendizagem em Sistemas Multi-Agente são consideradas duas áreas promissoras mas relativamente pouco exploradas. A optimização nestes ambientes deve ser capaz de lidar com o dinamismo. Os agentes podem alterar o seu comportamento baseando-se em aprendizagem recente ou em objectivos de optimização. As estratégias de aprendizagem podem melhorar o desempenho do sistema, dotando os agentes da capacidade de aprender, por exemplo, qual a técnica de optimização é mais adequada para a resolução de uma classe particular de problemas, ou qual a parametrização é mais adequada em determinado cenário. Nesta dissertação são estudadas algumas técnicas de resolução de problemas de Optimização Combinatória, sobretudo as Meta-heurísticas, e é efectuada uma revisão do estado da arte de Aprendizagem em Sistemas Multi-Agente. É também proposto um módulo de aprendizagem para a resolução de novos problemas de escalonamento, com base em experiência anterior. O módulo de Auto-Optimização desenvolvido, inspirado na Computação Autónoma, permite ao sistema a selecção automática da Meta-heurística a usar no processo de optimização, assim como a respectiva parametrização. Para tal, recorreu-se à utilização de Raciocínio baseado em Casos de modo que o sistema resultante seja capaz de aprender com a experiência adquirida na resolução de problemas similares. Dos resultados obtidos é possível concluir da vantagem da sua utilização e respectiva capacidade de adaptação a novos e eventuais cenários.

Sistema de apoio à geração de ideias em grupo considerando as emoções e os aspectos sociais

As emoções dos indivíduos e o contexto social do grupo onde estes estão inseridos têm influência no seu desempenho no que se refere ao desenvolvimento de várias tarefas, incluindo as que são realizadas via electrónica. O processo de geração de ideias em grupo mediado por computador tem vantagens consideráveis em relação ao processo de geração de ideias em grupo tradicional, nomeadamente no que se refere ao aumento da sinergia entre os elementos do grupo, à existência da memória de grupo e à possibilidade dos elementos estarem dispersos no espaço e no tempo. Com isto em mente, o presente trabalho pretende analisar a importância do estado de espírito do participante e a influência que os vários aspectos sociais têm no participante, para assim ser possível tomar determinadas acções com o objectivo de potenciar o desempenho dos utilizadores ao longo da reunião de geração de ideias. Neste trabalho é analisada a influência que o estado de espírito dos participantes e o contexto social das reuniões podem ter no sucesso de uma reunião de geração de ideias electrónica. Considerando a influência de estes factores, é proposto um modelo que inclui essas variáveis no processo de geração de ideias em grupo mediado por computador. Com isto pretende-se demonstrar que a inclusão do modelo proposto numa ferramenta de apoio à geração de ideias em grupo permite melhorar o desempenho individual e consequentemente o desempenho do grupo, bem como a interacção entre todos os elementos. Assim, este trabalho pretende gerar sugestões com o objectivo de manter os participantes atentos e motivados para as tarefas que têm de realizar, nomeadamente a tarefa de geração de ideias. Com o objectivo de aplicar o modelo proposto é também apresentado neste trabalho uma nova ferramenta de geração de ideias em computador que considera o contexto emocional e social da reunião, o S-IGTAI (Social Idea Generation Tool for Ambient Intelligence). Através das interacções entre os participantes e a ferramenta S-IGTAI, é recolhida informação que será o input do modelo proposto, sendo que o output serão as sugestões enviadas para o facilitador. Estas sugestões têm o propósito que o facilitador realize recomendações aos participantes no sentido de manter os seus estados de espírito num nível positivo e eliminar a influência negativa dos vários aspectos sociais, potenciando dessa forma o desempenho de todos os participantes. Com a finalidade de validar o modelo proposto e a nova ferramenta (S-IGTAI) é apresentado um caso de estudo neste documento que permite realizar a avaliação do trabalho desenvolvido.

Mudança linguística em português: aspectos sociolinguísticos da neologia

Neste estudo, proponho-me reflectir sobre o conceito de neologismo, com vista a analisar o contributo deste fenómeno para a mudança linguística do português. Discutirei a relevância de alguns dos critérios propostos por Cabré (1993) e pela Rede Panlatina de Terminologia para a identificação do fenómeno neológico, sustentandome na observação de dados linguísticos relacionados com o domínio da aprendizagem electrónica. É meu propósito ponderar as motivações sociolinguísticas da neologia e analisar possíveis implicações deste processo de criação lexical no tecido linguístico português contemporâneo e no contexto educativo do ensino superior.

Como convive a interpretação com os aspectos não verbais da comunicação

Neste artigo procuramos abordar a importância da comunicação não verbal na interpretação e as dificuldades provenientes da sua articulação com a linguagem verbal, neste âmbito. Apresenta-se um elenco seleccionado de recursos não verbais considerados essenciais e frequentes com os quais o profissional desta área se pode confrontar e sugerem-se algumas formas de como/quando os integrar na interpretação.