1,721,003 research outputs found
Tumor suppressor p16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells.
Alterations in DNA methylation are important in cancer, but the acquisition of these alterations is poorly understood. Using an unbiased global screen for CpG island methylation events, we have identified a non-random pattern of DNA hypermethylation acquired in p16-repressed cells. Interestingly, this pattern included loci located upstream of a number of homeobox genes. Upon removal of p16(INK4A) activity in primary human mammary epithelial cells, polycomb repressors, EZH2 and SUZ12, are up-regulated and recruited to HOXA9, a locus expressed during normal breast development and epigenetically silenced in breast cancer. We demonstrate that at this targeted locus, the up-regulation of polycomb repressors is accompanied by the recruitment of DNA methyltransferases and the hypermethylation of DNA, an endpoint, which we show to be dependent on SUZ12 expression. These results demonstrate a causal role of p16(INK4A) disruption in modulating DNA hypermethylation, and identify a dynamic and active process whereby epigenetic modulation of gene expression is activated as an early event in breast tumor progression
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
Identification of human papillomavirus DNA in cutaneous lesions of Cowden syndrome
Background: Cowden syndrome (CS) or multiple hamartoma syndrome is a cancer-associated genodermatosis inherited in an autosomal dominant pattern. One of the diagnostic criteria is facial papules which are felt to be trichilemmomas, benign hair follicle tumors, which some consider to be induced by human papillomavirus (HPV). Objective: To search for HPV in skin tumors, especially trichilemmomas, from patients with CS. Methods: Skin lesions from patients with CS were classified histologically. Each tumor was then analyzed for HPV DNA by polymerase chain reaction with different primer sets; positive amplicons were typed by direct sequencing. Results: Twenty-nine biopsies from 7 patients with CS were investigated. Only 2 of 29 tumors clinically suspected of being trichilemmomas were confirmed histologically. In addition, 3 sclerotic fibromas, also typical of CS, were found, as well as 1 sebaceous hyperplasia. The other 23 lesions showed histological features of HPV-induced tumors in various stages of development. HPV DNA was found in 19 of 29 cutaneous lesions. Tumors without any histological signs of HPV induction were negative for HPV DNA. Two tumors which were histologically classified as common warts contained HPV types 27 and 28. All the 17 other HPV types belong to the group of epidermodysplasia-verruciformis-associated types. Conclusions: The majority of cutaneous lesions in CS contain HPV DNA. They may have a variety of histological patterns. Trichilemmomas are not clinically distinctive and can be difficult to identify in CS patients. Copyright (C) 2003 S. Karger AG, Basel
Variations on the Author
“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
We 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
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