1,720,970 research outputs found
FUNCTIONAL CHARACTERIZATION OF THE ENDOCYTIC PROTEIN EPSIN3 IN BREAST CANCER
Endocytosis plays a critical role in the maintenance of cellular homeostasis. Due to its ability to resolve extracellular signals, the endocytic pathway controls many cellular processes, including transcription, proliferation, cell migration and cell fate determination. One relevant, unanswered, question regarding the role of endocytosis in the cell is whether subversion of the endocytic route is involved in the development of pathological conditions, such as cancer. This possibility is supported by studies showing altered expression of several endocytic proteins in human tumors. In a previous study in our lab, the endocytic protein Epsin 3 (Epn3) was found in a gene signature prognostic for metastatic breast cancer. Epn3 belongs to the Epsin family of endocytic proteins. Unlike the other Epsin members, Epn1 and Epn2, which are ubiquitously expressed, Epn3 is exclusively expressed in gastric cells and in wounded or pathological tissues exhibiting altered cell-extracellular matrix interactions. While Epn1 and Epn2 have been well characterized as endocytic adaptors, the exact function of Epn3 protein in endocytosis or signaling is largely unknown.
In the present study, we show that Epn3 is overexpressed in approximately 30% of breast tumors and that upregulation of this protein correlates with clinico-pathological parameters of aggressive disease. We also show that EPN3 gene is amplified in human breast tumors and that this genetic alteration can occur independently from HER2 amplification in these tumors. Through functional studies using in vitro and in vivo breast cancer models, we demonstrate that breast tumor cells harboring Epn3 amplification/overexpression are dependent on Epn3 deregulation for the maintenance of their tumorigenic potential. In agreement with a possible oncogenic role, overexpression of Epn3 in a breast tumor cell line increases the tumorigenic potential in vivo. Of note, Epn3 overexpression is also able to induce, both in normal and tumor breast cells, transcriptional and morphological changes typical of an epithelial-to-mesenchymal transition (EMT), in a TGFβ−dependent manner; indeed, Epn3 overexpression induces upregulation of TGFβ ligands and receptors and inhibition of TGFβ signaling is able to revert Epn3-induced EMT. In addition, we show that Epn3 increases the capacity of normal mammary epithelial cells to form mammospheres in vitro, suggesting that Epn3 may contribute to the expansion of the breast cancer stem cell compartment. Finally, we demonstrate that Epn3 is involved in E-cadherin internalization, by inducing its downregulation from the cell surface upon TGFβ-stimulation.
In conclusion, our data suggest a novel oncogenic role for Epn3 in human breast cancer, through its action as an endocytic protein on E-cadherin trafficking. Overexpression of Epn3 might enhance E-cadherin internalization, and consequently induce EMT activating the expression of mesenchymal proteins that promote cell invasion and lead to tumor aggressiveness
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
Analysis of 1H and 13C NMR spectra of cis and trans 10-Cl decal-2-ones by 2D NMR techniques.
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
Dispelling the Myths Behind First-author Citation Counts
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
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