1,721,146 research outputs found
HDAC4 mediates the crosstalk between skeletal muscle and fibro adipogenic progenitors in Duchenne Muscular Dystrophy
No full textDuchenne muscular dystrophy (DMD) is an X-linked, progressive, muscle-wasting disease caused by the lack of the dystrophin protein. The absence of dystrophin compromises muscle integrity leading to the substitution of skeletal muscle fibers with fibrotic and adipose tissues. This is due to the altered activity of a mesenchymal stem cell population, named fibro-adipogenic progenitors (FAPs). FAPs are the main cellular target of Givinostat, a pan-histone deacetylase inhibitor, recently approved by the FDA as a treatment for DMD patients. However, deletion of histone deacetylase 4 (HDAC4) in mdx muscles worsens DMD progression, demonstrating the importance of preserving the functions of this specific HDAC in dystrophic skeletal muscle.
The main objective of my Ph.D. project is to characterize in detail multiple functions of HDAC4 in skeletal muscle in DMD, focusing on the crosstalk between muscle fibers and FAPs.
We found that dystrophic mice lacking HDAC4 (mdx;KO) exhibit higher fibrotic and adipose tissue infiltration in the musculature than mdx littermates. Consistently, FAPs isolated from mdx;KO mice display a higher fibrotic and adipogenic potential. We hypothesized a paracrine function of HDAC4 which is mediated by EVs. Thus, we expressed the muscle-specific, cytoplasmic-restricted form of HDAC4 and noticed that this reduces the levels of fibrotic and adipose tissues in mdx;KO muscles, in addition to reducing muscle degeneration. All of the above, in addition to showing an effect which is independent of the deacetylase activity of HDAC4, confirms the importance of preserving its cytoplasmic functions in DMD. Proteomic and non-coding RNA transcriptomic analyses identified interesting candidates differentially secreted between mdx and mdx;KO myofibers, i.e. adiponectin and miR-5106, that may be crucial mediators of the paracrine functions of HDAC4 in DMD skeletal muscle
3D culture system to evaluate the impact of microgravity on the male gonad
No full textRATIONALE: One of the most important hazards of space environment is Microgravity, which causes alterations in the physiology of various systems, including the reproductive one. It has been observed that testicular cells appear to be sensitive to microgravity: 1) testicular endocrine functions are impaired during space missions since a decrease of testosterone production has been observed in astronauts; 2) even male germ cell models have been shown to be susceptible to changes in gravitational force. GENERAL OBJECTIVES: The general objective of the project is to set-up credible models to evaluate how microgravity induces alterations in testicular physiology and function. Indeed, to identify the molecular and cellular mechanisms underlying these alterations, different three-dimensional (3D) culture systems have been used. We focused our investigation on the following aspects: cell structure, cell to cell interactions, cell metabolism, cell oxidative stress, circadian rhythm genes expression level modifications, and cell endocrine/paracrine secretion. RESULTS: After 24h of Simulated Microgravity (SM) exposure, we observed in TCam-2 cell spheroids: 1) an increase of oxidative stress condition featured by high ROS levels, antioxidant barrier deregulation, and mitochondria enlargement; 2) an alteration of clock genes expression level possibly correlated with the aforementioned oxidative stress condition; 3) cell cytoskeleton and cell occluding junction alterations. After 24h of SM exposure, we observed in the testicular organ cultures: 1) an increase of testosterone and androstenedione levels in medium of culture without a significant change in Leydig cell mass; 2) an increase in protein expression level of enzymes involved in steroidogenesis: CYP17A1 and 17βHSD. CONCLUSIONS: These data indicate that TCam-2 spheroids are sensitive to SM exposure. Notably, with respect to the 2D model, investigated in previous studies, this system shows a better capacity to activate compensatory mechanisms in response to the alteration of gravitational force. Moreover, fetal testes organ cultures indicate that Fetal Leydig cells are sensible to SM being able to increase their androgen secretion probably because of the trigger of testicular mechano-sensing machiner
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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