1,720,976 research outputs found
Unveiling Histone Deacetylase 4 multiple functions in dystrophic skeletal muscle
Full text linkHistone deacetylase 4 (HDAC4) is a stress-responsive epigenetic factor able to mediate multiple cellular responses in skeletal muscle, upon different pathological conditions. The cytoplasmic functions of HDAC4 in skeletal muscle are poorly characterized so far. HDAC4 expression is upregulated in skeletal muscles of mdx mice, a mouse model for studying Duchenne Muscular Dystrophy (DMD), suggesting a role in this disease. DMD is a genetic, progressive disorder, characterized by muscle degeneration and weakness, ultimately leading to the premature death of patients. Pan-HDAC inhibitors are presently in clinical trial for the treatment of DMD, preventing fibrosis and adipogenesis and promoting compensatory regeneration, despite presenting several important limitations. The identification of the specific functions of different HDAC members is a prerequisite for the development of more selective drugs for the treatment of DMD. With the aim to clarify HDAC4 functions in DMD, we generated dystrophic mice with a skeletal muscle-specific deletion of HDAC4 (mdx;HDAC4mKO mice). Deletion of HDAC4 in skeletal muscle worsens the pathological features of DMD, increasing muscle damage and compromising muscle regeneration and function. HDAC4 affected Fibro Adipogenic Progenitors potential and decreased their ability to support mdx satellite cells, in addition to compromise mdx satellite cell differentiation via paracrine signals. Moreover, HDAC4 orchestrates membrane repair mechanism in mdx muscles and satellite cells, affecting muscle necrosis, satellite cell survival and myogenic capacity. Importantly, ectopic expression of Trim72, a major player in the membrane repair mechanism, or cytoplasmic HDAC4 rescues mdx;HDAC4mKO mice phenotype in vitro and in vivo. We demonstrated that HDAC4 cytoplasmic functions are independent of its deacetylase activity and crucial for allowing a proper response to muscle damage and preserving muscle homeostasis in DMD context. These findings should be considered for future therapeutic approaches
Coordinated actions of microRNAs with other epigenetic factors regulate skeletal muscle development and adaptation
Full text linkEpigenetics plays a pivotal role in regulating gene expression in development, in response to cellular stress or in disease states, in virtually all cell types. MicroRNAs (miRNAs) are short, non-coding RNA molecules that mediate RNA silencing and regulate gene expression. miRNAs were discovered in 1993 and have been extensively studied ever since. They can be expressed in a tissue-specific manner and play a crucial role in tissue development and many biological processes. miRNAs are responsible for changes in the cell epigenome because of their ability to modulate gene expression post-transcriptionally. Recently, numerous studies have shown that miRNAs and other epigenetic factors can regulate each other or cooperate in regulating several biological processes. On the one hand, the expression of some miRNAs is silenced by DNA methylation, and histone modifications have been demonstrated to modulate miRNA expression in many cell types or disease states. On the other hand, miRNAs can directly target epigenetic factors, such as DNA methyltransferases or histone deacetylases, thus regulating chromatin structure. Moreover, several studies have reported coordinated actions between miRNAs and other epigenetic mechanisms to reinforce the regulation of gene expression. This paper reviews multiple interactions between miRNAs and epigenetic factors in skeletal muscle development and in response to stimuli or disease
The RNA helicase DDX5 cooperates with EHMT2 to sustain alveolar rhabdomyosarcoma growth
Full text linkRhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. The alveolar fusion positive subtype (FP-RMS) is the most aggressive and is mainly caused by the expression of PAX3/7-FOXO1 oncoproteins, which are chal-lenging pharmacological targets. Here, we show that the DEAD box RNA helicase 5 (DDX5) is overexpressed in alveolar RMS cells and that its depletion and pharmacological inhibition decrease FP-RMS viability and slow tumor growth in xenograft models. Mechanistically, we provide evidence that DDX5 functions upstream of the EHMT2/AKT survival signaling pathway, by directly interacting with EHMT2 mRNA, modulating its sta-bility and consequent protein expression. We show that EHMT2 in turns regulates PAX3-FOXO1 activity in a methylation-dependent manner, thus sustaining FP-RMS myoblastic state. Together, our findings identify another survival-promoting loop in FP-RMS and highlight DDX5 as a potential therapeutic target to arrest RMS growth
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
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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