1,720,976 research outputs found
Fuzzy protein-DNA interactions and beyond: A common theme in transcription?
Get PDFGene expression regulation requires both diversity and specificity. How can these two contradictory conditions be reconciled? Dynamic DNA recognition mechanisms lead to heterogeneous bound conformations, which can be shifted by the cellular cues. Here we summarise recent experimental evidence on how fuzzy interactions contribute to chromatin remodelling, regulation of DNA replication and repair and transcription factor binding. We describe how the binding mode continuum between DNA and regulatory factors lead to variable, multisite contact patterns; polyelectrolyte competitions; on-the-fly shape readouts; autoinhibition controlled by post- translational modifications or dynamic oligomerisation mechanisms. Increasing experimental evidence supports the rugged energy landscape of the bound protein-DNA assembly, modulation of which leads to distinct functional outcomes. Recent results suggest the evolutionary conservation of these combinatorial mechanisms with moderate sequence constraints in the malleable transcriptional machinery
TGF-β in cancer: Metabolic driver of the tolerogenic crosstalk in the tumor microenvironment
Get PDFOvercoming tumor immunosuppression still represents one ambitious achievement for cancer immunotherapy. Of note, the cytokine TGF-β contributes to immune evasion in multiple cancer types, by feeding the establishment of a tolerogenic environment in the host. Indeed, it fosters the expansion and accumulation of immunosuppressive regulatory cell populations within the tumor microenvironment (TME), where it also activates resident stromal cells and enhances angiogenesis programs. More recently, TGF-β has also turned out as a key metabolic adjuster in tumors orchestrating metabolic pathways in the TME. In this review, we will scrutinize TGF-β-mediated immune and stromal cell crosstalk within the TME, with a primary focus on metabolic programs
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
Biomarkers of the Antioxidant Response: A Focus on Liver Carcinogenesis
No full textMany studies have demonstrated the association of oxidative stress caused by excessive and sustained production of reactive species with chronic inflammatory conditions, neurodegenerative diseases, diabetes mellitus, atherosclerosis, and cancer. The main mechanism of redox control relies on the cellular antioxidant response. Nevertheless, oxidative stress and oxidative damage to biomolecules are events inherent to the process of carcinogenesis. Antioxidant response systems do not operate in isolation, as there is significant convergence among thermodynamically favored systems. Three main systems may be identified: glutathione, thioredoxins (TRX), and nicotinamide adenine dinucleotide phosphate (NADPH). Liver tumors frequently exhibit overexpression of one or more proteins belonging to the antioxidant system, for example, glutathione reductase (GSR), glutathione S-transferase P (GSTP), gamma-glutamyl transferase (GGT), glucose-6-phosphate dehydrogenase (G6PD), thioredoxin reductase (TXNR), NAD(P)H dehydrogenase [quinone] 1 (NQO1), and prostaglandin reductase 1 (PTGR1). The increased expression of these enzymes is suggested as biomarker that favors tumor development by stimulating proliferation, angiogenesis, and metastasis or by preventing cell death. The loss of expression of some antioxidant enzymes could be used as biomarkers too such as catalase (CAT) and superoxide dismutase (SOD). Therefore, the expression of these proteins shows predictive value for the prognosis and risk of liver cancer recurrence in patients. In this chapter, we discuss the most recent findings regarding the enzymatic antioxidant cellular response that occurs during liver carcinogenesis and how these systems could be used as biomarkers in the clinical practice
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
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