1,720,968 research outputs found
Chromatin remodelling and epigenetic state regulation by non-coding RNAs in the diseased heart
: Epigenetics refers to all the changes in phenotype and gene expression which are not due to alterations in the DNA sequence. These mechanisms have a pivotal role not only in the development but also in the maintenance during adulthood of a physiological phenotype of the heart. Because of the crucial role of epigenetic modifications, their alteration can lead to the arise of pathological conditions. Heart failure affects an estimated 23 million people worldwide and leads to substantial numbers of hospitalizations and health care costs: ischemic heart disease, hypertension, rheumatic fever and other valve diseases, cardiomyopathy, cardiopulmonary disease, congenital heart disease and other factors may all lead to heart failure, either alone or in concert with other risk factors. Epigenetic alterations have recently been included among these risk factors as they can affect gene expression in response to external stimuli. In this review, we provide an overview of all the major classes of chromatin remodellers, providing examples of how their disregulation in the adult heart alters specific gene programs with subsequent development of major cardiomyopathies. Understanding the functional significance of the different epigenetic marks as points of genetic control may be useful for developing promising future therapeutic tools
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
Assessment of myocardial viability in patients with post-ischemic LV dysfunction: role of myocardial contrast echo
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
m6A modification regulates early human cardiomyocyte lineage specification
Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 813716. Background RNA modifications affect gene expression through the regulation of RNA metabolism. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification that occurs in RNAs. Its dynamic expression is regulated by the "writer complex" (methyltransferases) and "erasers" (demethylases) and affects numerous biological functions, including mammalian embryonic stem cell (ESC) fate specification. However, the role of m6A in human cardiomyocyte (CM) lineage specification remains unclear. Purpose In this study, we aim to investigate the impact of m6A modification on early human cardiomyocyte differentiation, following the dynamic expression of m6A modification of human induced pluripotent stem cells (hiPSC) into cardiomyocytes (hiPSC-CMs). Methods hiPSCs were differentiated into hiPSC-CMs by mesodermal induction, followed by inhibition of WNT-signaling. We collected hiPSC derivates at different stages of the differentiation protocol: hiPSCs, hiPSC-derived cardiac mesoderm cells, hiPSC-derived cardiomyocyte progenitors (hiPSC-CPCs), and mature hiPSC-CMs. Protein levels of m6A key regulators were analyzed. To systematically profile the expression of m6A modification, we subjected hiPSC derivates to m6A immunoprecipitation combined with deep sequencing (MeRIP-seq) and RNA-seq. Enrichment analyses of gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were conducted to elucidate the biological significance of differentially expressed and methylated genes. Results m6A distribution analysis on hiPSC derivates revealed a conserved pattern on a transcriptome-wide level: methylation sites are mainly located nearby the stop coding regions. However, we observed upregulated levels of writer proteins during the transition of hiPSC-derived cardiac mesoderm cells into hiPSC-CPCs. Interestingly, the dynamic changes in writer protein levels toward hiPSC-CPC transition were accompanied by a higher number of significantly upregulated and hyper-methylated mRNA transcripts. GO and KEGG analyses indicated hyper-methylated upregulated transcripts are enriched in muscle cell differentiation, cardiac physiology and calcium and MAPK signaling pathways regulating heart contraction. Conclusion For the first time, our study provides evidence that m6A modification is a mediator of early human cardiomyocyte differentiation. The role of specific writer regulators and individual m6A transcripts will be further investigated
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
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