1,720,992 research outputs found
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
Metformin dysregulates the unfolded protein response and the WNT/β-catenin pathway in endometrial cancer cells through an AMPK-independent mechanism
No full textMultiple lines of evidence suggest that metformin, an antidiabetic drug, exerts an-ti-tumorigenic effects in different types of cancer. Metformin has been reported to affect cancer cells’ metabolism and proliferation mainly through the activation of AMP-activated protein kinase (AMPK). Here, we show that metformin inhibits, indeed, endometrial cancer cells’ growth and induces apoptosis. More importantly, we report that metformin affects two important pro-survival pathways, such as the Unfolded Protein Response (UPR), following endoplasmic reticulum stress, and the WNT/β-catenin pathway. GRP78, a key protein in the pro-survival arm of the UPR, was indeed downregulated, while GADD153/CHOP, a transcription factor that mediates the pro-apoptotic response of the UPR, was upregulated at both the mRNA and protein level. Fur-thermore, metformin dramatically inhibited β-catenin mRNA and protein expression. This was paralleled by a reduction in β-catenin transcriptional activity, since metformin inhibited the activity of a TCF/LEF-luciferase promoter. Intriguingly, compound C, a well-known inhibitor of AMPK, was unable to prevent all these effects, suggesting that metformin might inhibit endometrial cancer cells’ growth and survival through the modulation of specific branches of the UPR and the inhibition of the Wnt/β-catenin pathway in an AMPK-independent manner. Our findings may provide new insights on the mechanisms of action of metformin and refine the use of this drug in the treatment of endometrial cancer
Targetting PED/PEA-15 for diabetes treatment
No full textPED/PEA-15 is an ubiquitously expressed protein, involved in the regulation of proliferation and apoptosis. It is commonly overexpressed in Type 2 Diabetes (T2D) and in different T2D-associated comorbidities, including cancer and certain neurodegenerative disorders. Areas covered: In mice, Ped/Pea-15 overexpression impairs glucose tolerance and, in combination with high fat diets, further promotes insulin resistance and T2D. It also controls β-cell mass, altering caspase-3 activation and the expression of pro- and antiapoptotic genes. These changes are mediated by PED/PEA-15-PLD1 binding. Overexpression of PLD1 D4 domain specifically blocks Ped/Pea-15-PLD1 interaction, reverting the effect of Ped/Pea-15 in vivo. D4α, a D4 N-terminal peptide, is able to displace Ped/Pea-15-PLD1 binding, but features greater stability in vivo compared to the entire D4 peptide. Here, we review early mechanistic studies on PED/PEA-15 relevance in apoptosis before focusing on its role in cancer and T2D. Finally, we describe potential therapeutic opportunities for T2D based on PED/PEA-15 targeting. Expert opinion: T2D is a major problem for public health and economy. Thus, the identification of new molecules with pharmacological activity for T2D represents an urgent need. Further studies with D4α will help to identify smaller pharmacologically active peptides and innovative molecules of potential pharmacological interest for T2D treatment
Potential Mechanisms of Bisphenol A (BPA) Contributing to Human Disease
No full textBisphenol A (BPA) is an organic synthetic compound serving as a monomer to produce polycarbonate plastic, widely used in the packaging for food and drinks, medical devices, thermal paper, and dental materials. BPA can contaminate food, beverage, air, and soil. It accumulates in several human tissues and organs and is potentially harmful to human health through different molecular mechanisms. Due to its hormone-like properties, BPA may bind to estrogen receptors, thereby affecting both body weight and tumorigenesis. BPA may also affect metabolism and cancer progression, by interacting with GPR30, and may impair male reproductive function, by binding to androgen receptors. Several transcription factors, including PPARγ, C/EBP, Nrf2, HOX, and HAND2, are involved in BPA action on fat and liver homeostasis, the cardiovascular system, and cancer. Finally, epigenetic changes, such as DNA methylation, histones modification, and changes in microRNAs expression contribute to BPA pathological effects. This review aims to provide an extensive and comprehensive analysis of the most recent evidence about the potential mechanisms by which BPA affects human health
Circulating miRNAs as intercellular messengers, potential biomarkers and therapeutic targets for Type 2 diabetes
No full textmiRNAs have emerged as key epigenetic regulators of metabolism. Their deregulation contributes to metabolic abnormalities, proposing their potential role as therapeutic targets for Type 2 diabetes. The exciting finding that miRNAs exist in the bloodstream suggests that circulating miRNAs may act in a hormone-like fashion. Despite the fact that significant progress has been made in understanding circulating miRNAs, this topic is full of complexities and many questions remain unanswered. The goal of this review is to bring together up-to-date knowledge about circulating miRNAs and their role as intercellular communicators as well as potential biomarkers and therapeutic targets in metabolic diseases, providing examples of possible clinical applications for circulating miRNAs in diabetes and cardiovascular complications
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
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