1,720,969 research outputs found
ROLE OF HMGA1 IN BREAST CANCER AGGRESSIVENESS
No full textBreast cancer is the most common cancer in women and a leading cause of cancer mortality worldwide, mainly due to metastatic progression. Although in the last years cancer has become more curable, the path to eradicate it, is still long and convolute. Understanding molecular mechanisms that induce and support cancer progression and aggressiveness is crucial to find new targets and drugs to treat it. High Mobility Group A1 (HMGA1) protein is an oncofetal architectural chromatin factor that promotes neoplastic transformation and progression but its role in breast cancer aggressiveness is still unclear. The aim of this thesis was to unravel the involvement of HMGA1 in this disease highlighting which pathways are intersected. Thus, working on basal-like breast cancer subtype, we demonstrated that HMGA1 plays a crucial role in conferring metastatic traits. Indeed, HMGA1 silencing reduces migration and invasion properties in vitro and metastasis formation in vivo with a concomitant mesenchymal to epithelial transition and decreases stem cell properties and self-renewal activity. We performed microarray analysis in cells expressing or depleted for HMGA1 and we identified a specific 130-HMGA1 gene signature associated with poor prognosis. This analysis allowed us to identify pathways, controlled by HMGA1 and known to be involved in aggressiveness traits, such as Wnt/beta-catenin and Notch. Moreover, among the genes present in the 130-HMGA1 gene signature we deepen the relationship between HMGA1 and CCNE2, one of the gene most correlated with clinical outcome. We showed that CCNE2 acts downstream HMGA1 to regulate the migration and invasion proprieties of basal-like breast cancer cells. Moreover, we demonstrated that CCNE2 action is mediated by the oncogene YAP, the downstream effector of the Hippo pathway. Indeed, knock down of both HMGA1 and CCNE2 impaired nuclear localization and activity of YAP, acting upstream of the Hippo pathway core kinases MST1/2 and LATS1/2. Moreover, in breast cancer patients, HMGA1 and CCNE2 expression was associated with YAP/TAZ signature further supporting this connection. Because CDKs are the main partners of CCNE2, we blocked their activity using CDK inhibitors in order to impair HMGA1-CCNE2-YAP axis and we demonstrated a decrease in cell migration and an induction of translocation of YAP from nucleus to cytoplasm. Therefore, this thesis highlights the involvement of HMGA1 in breast cancer metastasis through the interplay with different pathways. In particular, we identified for the first time a role of HMGA1 in regulating YAP through the modulation of the Hippo pathway
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“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
Full text linkWe 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
Full text linkWe 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
A novel HMGA1-CCNE2-YAP axis regulates breast cancer aggressiveness
Full text linkHigh Mobility Group A1 (HMGA1) is an architectural chromatin factor that promotes neoplastic transformation and progression. However, the mechanism by which HMGA1 exerts its oncogenic function is not fully understood. Here, we show that cyclin E2 (CCNE2) acts downstream of HMGA1 to regulate the motility and invasiveness of basal-like breast cancer cells by promoting the nuclear localization and activity of YAP, the downstream mediator of the Hippo pathway. Mechanistically, the activity of MST1/2 and LATS1/2, the core kinases of the Hippo pathway, are required for the HMGA1- and CCNE2-mediated regulation of YAP localization. In breast cancer patients, high levels of HMGA1 and CCNE2 expression are associated with the YAP/TAZ signature, supporting this connection. Moreover, we provide evidence that CDK inhibitors induce the translocation of YAP from the nucleus to the cytoplasm, resulting in a decrease in its activity. These findings reveal an association between HMGA1 and the Hippo pathway that is relevant to stem cell biology, tissue homeostasis, and cancer
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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