1,720,958 research outputs found
Analysis of the association between genetic polymorphisms in TP53 and XRCC1 and characteristics of cases of breast cancer
No full textO câncer de mama é o tipo de câncer mais comum em mulheres brasileiras e o principal responsável pelos óbitos neste grupo. Segundo dados do Instituto Nacional do Câncer, em 2008, na região Sudeste do Brasil, o câncer de mama foi o
mais incidente, com um risco estimado de 68,12 casos novos por 100 mil. No Estado do Rio de Janeiro a estimativa foi de 7.680 casos, sendo 4.160 na capital. O presente estudo teve como objetivo determinar, através da metodologia de PCRRFLP,
as freqüências alélicas e genotípicas dos polimorfismos PIN3 Ins 16pb e Arg72Pro, do gene TP53, e Arg194Trp e Arg399Gln, do gene XRCC1, em 105 casos de câncer de mama e analisar a relação entre esses polimorfismos e os dados sócio-demográficos das pacientes, a história familiar de câncer de mama e as características clínico-patológicas do tumor. Por esta razão, neste estudo realizamos um estudo do tipo caso-caso, utilizando-se pacientes diagnosticadas com carcinoma
ductal infiltrante. Em relação ao papel desses polimorfismos genéticos no prognóstico da doença, foi observada uma associação da variante Arg194Trp de XRCC1 com a agressividade do tumor através de uma correlação positiva com o grau de Elston III (OR = 3,99; IC 95% 1,08 14,66; p = 0,044). Análises subseqüentes contando com um número maior de indivíduos podem auxiliar na confirmação deste achado e na elucidação do papel da variante Trp194 no prognóstico do câncer de mama.Breast cancer is the most common cancer in Brazilian women and the main responsible for their cancer death. According to data of the National Institute of Cancer, in 2008, in the Southeast region of Brazil, breast cancer had the highest incidence with an estimated risk of 68.12 new cases in one hundred thousand. In the State of Rio de Janeiro, the estimative was of 7.680 cases, 4.160 of them in the capital. The present study aimed to determine, through PCR-RFLP methodology, the alleles and genotypes frequencies of the polymorphisms PIN3 Ins 16pb and Arg72Pro, in the TP53 gene; Arg194Trp and Arg399Gln, in the XRCC1 gene, in 105 cases of breast cancer, and analyze the relationship between these polymorphisms and patients socio-demographic data, family history of breast cancer and tumor clinicopathological characteristics. Hence, in this study we performed a case-case study, using patients diagnosed with infiltrating ductal carcinoma. In respect with the role of these genetic polymorphisms in breast cancer prognosis, it was observed an association with the variant Arg194Trp of XRCC1 and tumor aggressiveness by a positive correlation with Elston grade III (OR = 3.99; CI 95% 1.08 14.66; p = 0.044). Further analyses including a larger group of study can help to confirm this finding and elucidate the role of Trp194 variant in breast cancer prognosis
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
MARs chromatin study on <i>TP53</i> gene domain and epigenetic modifications in a breast cancer progression model
No full textDentre os diversos tipos de câncer agressivos, o câncer de mama é o mais comum em mulheres. Mutações hereditárias e adquiridas, assim como alterações epigenéticas atuam em sinergia na carcinogênese mamária e na progressão tumoral. A proteína P53 é uma supressora de tumor e possui uma atuação fundamental na integridade genômica. Apesar do vasto conhecimento sobre o controle da P53 a nível de proteína, ainda pouco se sabe sobre o controle transcricional do gene <i>TP53</i>. A série 21T, uma série de 4 linhagens celulares originadas da mama da mesma paciente, representando diferentes estágios de progressão tumoral mamária, é um eficiente modelo para investigação das alterações epigenéticas e suas influências na expressão gênica ao longo da progressão do câncer de mama. Nós analisamos a organização do domínio do gene <i>TP53</i> através da técnica de arranjo de DNA, em diversas linhagens celulares de câncer de mama e linhagens controle, e realizamos uma tentativa de caracterizar estes elementos de DNA nas linhagens controle não-tumorais HB2 e MCF10A e nas tumorais MCF-7, MDA-MB-231, T47D, através dos marcadores epigenéticos de eucromatina, H4Ac, e heterocromatina, H3K9me3. Ainda analisamos a ligação de proteínas à região associada à matriz nuclear (MAR), denominada MAR 2, e a possível ligação da proteína ligante à matriz nuclear (MARBP), PARP-1, através de ensaios de gel shift (EMSA). Detectamos que na linhagem controle epitelial mamária, HB2, o gene <i>TP53</i> está posicionado num domínio de DNA relativamente pequeno, aproximadamente 50 kb, delimitado por dois sítios de fixação à matriz nuclear. Interessantemente, esta estrutura de domínio se apresentou radicalmente diferente nas linhagens de câncer de mama estudadas, MCF7, T47D, MDA-MB-231 e BT474, nos quais o tamanho do domínio estudado estava aumentado e a transcrição do <i>TP53</i> diminuída. Os enriquecimentos com os marcadores epigenéticos de cromatina H4Ac e H3K9me3 estão diferentemente distribuídos nas MARs nas linhagens celulares. Surpreendentemente, a MAR 2 apresentou uma ligação altamente específica, o que poderia representar a atuação de fatores transcricionais envolvidos na organização da cromatina. Através de programas de bioinformática, detectamos putativos sítios para interessantes fatores de transcrição, tais como o c/EBP-beta e c-myb, que poderiam atuar em cis regulando a expressão do gene <i>TP53</i> e outros flanqueadores. Nós propusemos um modelo para a organização da cromatina na região de domínio do gene <i>TP53</i> com os genes flanqueadores. Através da série 21T, detectamos uma hipometilação global genômica, nas células cancerosas 21NT e 21MT1. Uma importante diminuição da expressão global do marcador H4Ac nas células metastáticas 21MT1, foi detectada em relação às outras linhagens. Os níveis de RNAm das principais enzimas relacionadas as modificações epigenéticas são consistentes com as observadas hipometilação genômica e hipoacetilação. Através de microscopia confocal, verificamos que o marcador H4Ac está localizado, na maior parte na periferia e o marcador H3K9me3, pericêntrico nos núcleos tumorais. Por fim, verificamos que o promotor P1 do gene <i>TP53</i> apresenta um estado de cromatina aberta, e a expressão do gene <i>TP53</i> é similar em todas as células da série 21T.Breast cancer is the most common aggressive cancer type in women. Inherited and acquired mutations as well as epigenetic alterations act together in breast carcinogenesis and tumor progression. P53 is a tumor suppressor protein critical for genome integrity. Although its control at the protein level is well known, the transcriptional regulation of the <i>TP53</i> gene is still unclear. The 21T series, a series of 4 breast cell lines originating from the same patient and representative of the breast tumor progression stages, is a suitable model to investigate epigenetic alterations and their influences upon gene expression during breast tumor progression. We have analyzed the organization of the <i>TP53</i> gene domain using DNA arrays in several breast cancer and control cell lines and we made an attempt to characterize these DNA elements in breast non-cancerous cell lines HB2 and MCF-10, and cancerous MCF-7, MDA-MB-231 and T47D, through the determination of epigenetic markers of euchromatin, H4Ac, and heterochromatin, H3K9me3. We further analyzed the matrix attachment region (MAR), named MAR 2, protein binding, and possible MAR 2 binding of the important MAR binding protein (MARBP), PARP-1, by Electrophoretic mobility Shift Assay (EMSA). We have found that in the control breast epithelial cell line, HB2, the <i>TP53</i> gene is positioned within a relatively small DNA domain, encompassing 50 kb, delimited by two nuclear matrix attachment sites. Interestingly, this domain structure was found to be radically different in the studied breast cancer cell lines, MCF7, T47D, MDA-MB-231 and BT474, in which the domain size was increased and <i>TP53</i> transcription was decreased. H4Ac and H3K9me3, chromatin epigenetic markers enrichment are differentially distributed through MARs in cell lines. Surprinsingly, MAR 2 presented a defined band-shift, which could represent trans-acting factor(s), involved in chromatin organization. By bioinformatics software, we found interesting transcription factors putative binding sites, such as for c/EBP-beta and c-myb, which could be cis-acting elements regulating <i>TP53</i> and neighboring genes expression. We propose a model for the chromatin organization of the <i>TP53</i> gene domain with neighboring genes. Through 21T cell line series, we detected a global genomic hypomethylation profile in the cancerous 21NT and 21MT1. An important global decrease of the active chromatin mark H4Ac in the metastatic 21MT1 relative to other cell lines was detected. mRNA levels of key enzymes linked to epigenetic modifications are consistent with the observed genomic hypomethylation and hypoacetylation. By confocal immunofluorescent assay we observed that H4Ac is mostly located at periphery, and the repressive mark H3K9Me3 located pericentric, in tumorigenic cells nuclei. <i>TP53</i> P1 promoter in 21T series was found to be in an open state and <i>TP53</i> transcription level was found to be similar in all 21T cell lines
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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