1,721,117 research outputs found
ROLE OF SMYD3 IN SKELETAL MUSCLE ATROPHY AND MOUSE EMBRYONIC STEM CELL
No full textEpigenetic regulation of gene expression plays a pivotal role in the establishment of developmental programs and the maintenance of the differentiated state. Among the different actors involved in this scenery, the modifications of histones tail are implicated with the propagation of gene expression patterns.
Our group is focused on SMYD3, a histone-methyltransferase which is reported to be is highly expressed in normal conditions only in the embryo, in adult skeletal muscle and in few other tissues. In light of SMYD3 restricted expression, we asked whether it might play a role during myogenesis and/or muscle maintenance but also when it plays its role during development.
We firstly have clarified the role of the histone-methyltransferase SMYD3 as a modulator of two factors involved in muscle-growth regulation and muscle atrophy, myostatin and c-Met transcription. Our results uncover a novel role for SMYD3 in recruiting the bromodomain protein BRD4. SMYD3 engages BRD4 and the positive transcription elongation factor complex (p-TEFb), triggering the phosphorylation on Serine 2 of the RNA Polymerase II, which favors the transcription elongation. Our data show that treatment with the BRD4 inhibitor JQ1 protects myotubes size reduction induced by dexamethasone administration and hinders pro-atrophic factors upregulation. These results suggest that JQ1 may represent a novel pharmacological avenue to alleviate muscle loss associated with muscle atrophy.
We then clarify the role played by SMYD3 in embryonic development. Recent study in zebrafish model suggests that SMYD3 plays an important role in the development of heart. Therefore we decided to investigate the role of SMYD3 by employing mouse embryonic stem cells (mESC) as a model of developmental differentiation toward cardiomyocytes. We observed that the expression levels of cardiac markers as well as cardiovascuolar progenitor markers were increased in SMYD3 depleted embryoid bodies. To further disclose the role of SMYD3 in embryoid bodies differentiation we also analyzed markers of the primitive streak and transcripts involved in EMT. We report the SMYD3 played a role during early stages of embryonic stem cells differentiation
Tackling skeletal muscle cells epigenome in the next-generation sequencing era
Full text linkRecent advances in high-throughput technologies have transformed methodologies employed to study cell-specific epigenomes and the approaches to investigate complex cellular phenotypes. Application of next-generation sequencing technology in the skeletal muscle differentiation field is rapidly extending our knowledge on how chromatin modifications, transcription factors and chromatin regulators orchestrate gene expression pathways guiding myogenesis. Here, we review recent biological insights gained by the application of next-generation sequencing techniques to decode the epigenetic profile and gene regulatory networks underlying skeletal muscle differentiation
The Bromodomain inhibitor JQ1 prevents skeletal muscle loss during cancer cachexia
No full textSkeletal muscle wasting is a hallmark of cancer cachexia. This metabolic
syndrome is responsible for about 25% of cancer deaths. In particular,
muscle loss in cachectic patients often leads to increased morbidity and
mortality, decreased beneficial effects from chemotherapeutic treatment,
and poorer quality of life. Therefore, the development of therapeutic
avenues addressed at preventing muscle wasting during cancer
cachexia is attracting increasing clinical interest. To date, no effective
therapies for cachectic muscle are available. Recently, our research group
reported that the small bromodomain inhibitor JQ1 enhances muscle fiber
size and protects from dexamethasone-induced muscle atrophy in
C2C12 myotubes, by blocking skeletal muscle pro-atrophic pathways, triggered
by myostatin. In the present work we evaluated the effect of JQ1
treatment in skeletal muscle wasting during cancer cachexia. To this
aim, C26 (adenocarcinoma cell line) bearing mice were chronically
treated with JQ1 or vehicle. After 12 days, body weight, skeletal muscle
weight and the anabolic/catabolic pathways involved in skeletal muscle
homeostasis were analyzed. The results show that JQ1 treatment blocks
muscle-specific ubiquitin ligases expression, and protects tumor-bearing
mice from body weight loss and muscle wasting. Furthermore, JQ1 administration
prevents adipose tissue loss and restores lipids levels in
the blood. These results suggest that the epigenetic modulation mediated
by bromodomain inhibitors may represent a promising therapeutic
approach in the management of muscle wasting during cancer cachexia
BRD4 modulates autophagy by regulating oxidative stress in skeletal muscle: physiopathological implications in Duchenne muscular dystrophy
No full text
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
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