Epstein-Barr virus detection in invasive and pre-invasive lesions of the uterine cervix

In the present study, our aim was to investigate whether EBV DNA could be found in association with invasive and pre-invasive cervical cancer lesions. We hypothesize that EBV is not merely a commensal agent when present in malignant cervical lesions. DNA was extracted from cervical scrapings followed by nested PCR-based amplification. The patients were 66 women with high grade cervical intraepithelial neoplasia and 14 women with invasive cervical cancer. The control group consisted of 89 women with a normal Pap smear and colposcopy as well as a negative HPV DNA test. Analysis of our results, in conjunction with the work of other authors, leads us to propose that EBV is not merely a commensal agent when present in malignant cervical lesions. The presence of DNA from EBV is significantly associated with cervical cancer.

Association of EGFR c.2073A > T polymorphism with decreased risk of diffusely infiltrating astrocytoma in a Brazilian case-control study

Epidermal growth factor receptor (EGFR) gene overexpression has been implicated in the development of many types of tumors, including glioblastomas, the most frequent diffusely infiltrating astrocytomas. However, little is known about the influence of the polymorphisms of EGFR on EGFR production and/or activity, possibly modulating the susceptibility to astrocytomas. This study aimed to examine the association of two EGFR promoter polymorphisms (c.-191C > A and c.-216G > T) and the c.2073A > T polymorphism located in exon 16 with susceptibility to astrocytomas, EGFR gene expression and survival in a case-control study of 193 astrocytoma patients and 200 cancer-free controls. We found that the variant TT genotype of the EGFR c.2073A > T polymorphism was associated with a significantly decreased risk of astrocytoma when compared with the AA genotype [sex- and age-adjusted odds ratio 0.51, 95% confidence interval 0.26-0.98]. No association of the two promoter EGFR polymorphisms (or combinations of these polymorphisms) and risk of astrocytomas, EGFR expression or survival was found. Our findings suggest that modulation of the EGFR c.2073A > T polymorphism could play a role in future therapeutic approaches to astrocytoma. (Int J Biol Markers 2008; 23: 140-6)

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein-protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation.

Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin

Proteomic approaches have been useful for the identification of aberrantly expressed proteins in complex diseases such as cancer. These proteins are not only potential disease biomarkers, but also targets for therapy. The aim of this study was to identify differentially expressed proteins in diffuse astrocytoma grade II, anaplastic astrocytoma grade III and glioblastoma multiforme grade IV in human tumor samples and in non-neoplastic brain tissue as control using 2-DE and MS. Tumor and control brain tissue dissection was guided by histological hematoxylin/eosin tissue sections to provide more than 90% of tumor cells and astrocytes. Six proteins were detected as up-regulated in higher grade astrocytomas and the most important finding was nucleophosmin (NPM) (p < 0.05), whereas four proteins were down-regulated, among them raf kinase inhibitor protein (RKIP) (p < 0.05). We report here for the first time the alteration of NPM and RKIP expression in brain cancer. Our focus on these proteins was due to the fact that they are involved in the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways, known for their contribution to the development and progression of gliomas. The proteomic data for NPM and RKIP were confirmed by Western blot, quantitative real-time PCR and immunohistochemistry. Due to the participation of NPM and RKIP in uncontrolled proliferation and evasion of apoptosis, these proteins are likely targets for drug development.

Dinoflagellate symbiosis: strategies and adaptations for the aquisition and fixation of inorganic carbon

Dinoflagellates exist in symbiosis with a number of marine invertebrates including giant clams, which are the largest of these symbiotic organisms. The dinoflagellates (Symbiodinium sp.) live intercellularly within tubules in the mantle of the host clam. The transport of inorganic carbon (Ci) from seawater to Symbiodinium (=zooxanthellae) is an essential function of hosts that derive the majority of their respiratory energy from the photosynthate exported by the zooxanthellae. Immunolocalisation studies show that the host has adapted its physiology to acquire, rather than remove CO2, from the haemolymph and clam tissues. Two carbonic anhydrase (CA) isoforms (32 and 70 kDa) play an essential part in this process. These have been localised to the mantle and gill tissues where they catalyse the interconversion of HCO3- to CO2, which then diffuses into the host tissues. The zooxanthellae exhibit a number of strategies to maximise Ci acquisition and utilisation. This is necessary as they express a form II Rubisco that has poor discrimination between CO2 and O-2. Evidence is presented for a carbon concentrating mechanism (CCM) to overcome. this disadvantage. The CCM incorporates the presence of a light-activated CA activity, a capacity to take up both HCO3- and CO2, an ability to accumulate an elevated concentration of Ci within the algal cell, and localisation of Rubisco to the pyrenoid. These algae also express both external and intracellular CAs, with the intracellular isoforms being localised to the thylakoid lumen and pyrenoid. These results have been incorporated into a model that explains the transport of Ci from seawater through the clam to the zooxanthellae.

Populações de plantas na cultura da soja em cultivares convencionais e Roundup ReadyTM

Este trabalho teve como objetivo estudar o comportamento de cultivares de soja convencionais e Roundup ReadyTM (RR) quando cultivados com diferentes populações de plantas por hectare. Foram realizados três ensaios no município de Jari, RS: em novembro de 2004 e de 2005 e em janeiro de 2006 (semeadura após a época indicada). Os cultivares convencionais utilizados foram: CEP/CD 41, CD 201, FUNDACEP 39 e CD 205 e os Roundup ReadyTM AL72, NK Mágica 7.3 RR e A 6001 RG nas populações de 250, 400 e 550 mil plantas ha-1. Em cada ensaio, o delineamento experimental utilizado foi blocos ao acaso, com 21 tratamentos e quatro repetições. Os tratamentos foram dispostos em esquema de parcelas subdivididas, representados pelos cultivares nas parcelas e pelas populações de plantas nas subparcelas. Foram avaliados a produtividade de grãos e os componentes da produção: legumes por planta e por m², peso de 100 grãos e número de grãos por legume. O comportamento dos cultivares convencionais e Roundup ReadyTM diferiu com a população de plantas. Em condição de estresse hídrico severo o aumento da população de plantas não afetou a produtividade. Somente o cultivar A 6001 RG apresentou rendimento estável nas diferentes populações de plantas, indicando que ele possui maior plasticidade. O número de legumes por planta foi reduzido com o aumento do número de plantas por área. As maiores produtividades foram alcançadas onde foi constatado maior número de legumes por m². O maior valor do peso de 100 grãos foi encontrado na maior população de plantas. O número de grãos por legume reduziu-se com o aumento da população de plantas. Condições de cultivo mais favoráveis tendem a aumentar o número de legumes/m², peso de 100 sementes e número de grãos por legume.

Da certeza e doublethink : Orwell e Wittgenstein

É meu objectivo, neste artigo, voltar a considerar a noção de Doublethink de Orwell, com referência ao pensamento posterior de Ludwig Wittgenstein. No mundo perturbado de Doublethink que Orwell descreve em Mil Novecentos e Oitenta e Quatro, muitas vezes parece que certeza sobre qualquer coisa se tornou impossível, estando tudo aberto à dúvida. Na verdade, defendo que a certeza é mais fundamental ao Doublethink do que a dúvida, e que Doublethink em Mil Novecentos e Oitenta e Quatro surge frequentemente porque as certezas das personagens chocam com coisas das quais seria muito mais lógico duvidar. Embora alguns aspectos do pensamento de Wittgenstein sobre crença pareceriam deixar muito pouco espaço para o fenómeno de Doublethink, noutros aspectos uma compreensão Wittgensteiniana de crença, conhecimento e certeza constitui uma boa posição para o analisar. Tanto Wittgenstein como Orwell exploram a relação entre verdade e conhecimento, certeza e crença como ligada à relação entre verdade e linguagem, comportamento e prática social.

O piano (bem) informado : processos de interiorização e crescimento

Este livro debruça-se sobre questões ligadas à metodologia do piano, incluindo aspectos técnicos, musicais e artísticos, num enquadramento que engloba algumas das principais reflexões éticas, estéticas e filosóficas de referência. O objetivo deste trabalho é a partilha de uma visão baseada na experiência pessoal e profissional na área do piano. Este texto assume uma certa continuidade com as grandes contribuições de autores tais como Ludwig Deppe, Matthay Tobias, Grigory Kogan, Heinrich Neuhaus e George Kochevitsky publicado. Ao mesmo tempo que se integra e complementa alguma dessa literatura especializada, aponta ideias, sugestões e pontos de vista caracterizados pela inovação e aplicabilidade racional e científica.

The (well) informed piano : internalization and growth process

The subject matter of this book is about piano methodology, including technical, musical, artistic, ethical and philosophical issues and reflections. The purpose of this work is to share a personal professional experience insight in the field of piano performance. This text assumes a certain continuity to the major contributions of artists like Ludwig Deppe, Tobias Matthay, Grigory Kogan, Heinrich Neuhaus and George Kochevitsky. At the same time, it tries to integrate and complement this selected literature, bringing new ideas and hints to specific professional issues.

Mining protein structure data

The principal topic of this work is the application of data mining techniques, in particular of machine learning, to the discovery of knowledge in a protein database. In the first chapter a general background is presented. Namely, in section 1.1 we overview the methodology of a Data Mining project and its main algorithms. In section 1.2 an introduction to the proteins and its supporting file formats is outlined. This chapter is concluded with section 1.3 which defines that main problem we pretend to address with this work: determine if an amino acid is exposed or buried in a protein, in a discrete way (i.e.: not continuous), for five exposition levels: 2%, 10%, 20%, 25% and 30%. In the second chapter, following closely the CRISP-DM methodology, whole the process of construction the database that supported this work is presented. Namely, it is described the process of loading data from the Protein Data Bank, DSSP and SCOP. Then an initial data exploration is performed and a simple prediction model (baseline) of the relative solvent accessibility of an amino acid is introduced. It is also introduced the Data Mining Table Creator, a program developed to produce the data mining tables required for this problem. In the third chapter the results obtained are analyzed with statistical significance tests. Initially the several used classifiers (Neural Networks, C5.0, CART and Chaid) are compared and it is concluded that C5.0 is the most suitable for the problem at stake. It is also compared the influence of parameters like the amino acid information level, the amino acid window size and the SCOP class type in the accuracy of the predictive models. The fourth chapter starts with a brief revision of the literature about amino acid relative solvent accessibility. Then, we overview the main results achieved and finally discuss about possible future work. The fifth and last chapter consists of appendices. Appendix A has the schema of the database that supported this thesis. Appendix B has a set of tables with additional information. Appendix C describes the software provided in the DVD accompanying this thesis that allows the reconstruction of the present work.

Synechocystis ferredoxin/ferredoxin-NADP+-reductase/NADP+ complex: Structural model obtained by NMR-restrained docking

FEBS Letters 579 (2005) 4585–4590

A further investigation of the cytochrome b5–cytochrome c complex

J Biol Inorg Chem (2003) 8: 777–786

Integrating protein structural information

Dissertação apresentada para obtenção de Grau de Doutor em Bioquímica,Bioquímica Estrutural, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Multiple sequence alignment correction using constraints

Trabalho apresentado no âmbito do European Master in Computational Logics, como requisito parcial para obtenção do grau de Mestre em Computational Logics