2,138 research outputs found
Early signaling events involved in muscle remodeling after exercise
No full textMuscle plasticity after exercise is achieved by different molecular mechanisms that regulate gene transcription by impinging on chromatin structure and transcription factors. Exercise is able to induce adaptive response to improve metabolic efficiency, oxidative capacity, and contractile activity by altering gene expression profile and protein levels. Nonetheless, the molecular mechanisms at the basis of these changes remain not very well characterized. The aim of our study is to dissect the early signaling events linked to skeletal muscle remodeling. To address this question we decided to divided the project in two parts.
First, we focused our attention on changes in the phosphoproteome after exercise and how this can affect gene transcription. In order to determine the global changes in the phosphoproteome after high intensity exercise we performed a quantitative phosphoproteomic analysis and we compared the stimulated (50 eccentric contraction) to the non-stimulated controlateral muscle. We identified a list of peptides with the strongest increase in phophorylation after eccentric contractions and in particular we found a significant increase in a previously uncharacterized phosphorylation site of myocardin-related transcription factor 2 (MRTF-B), the serine 77. The myocardin/MKL family of proteins has been described as strong coactivators of the Serum Response Factor (SRF), an important signaling pathway known to control skeletal muscle growth. It has been reported in various cell systems that the intracellular localization of MRTF-B is regulated by phosphorylation, enabling it to shuttle from the cytoplasm to the nucleus. We found that after eccentric contractions there is a nuclear accumulation of MRTF-B. Performing a point mutation, in which Serine 77 is replaced by an alanine, the nuclear accumulation of MRTF-B after eccentric contractions is completely abrogated. In order to understand if the nuclear accumulation of MRTF-B after eccentric contractions is also accompanied by an increase in SRF-dependent gene transcription, we performed a microarray analyses 24 hours after stimulation. Performing a gene set enrichment analyses (GSEA) on the differentially regulated genes, we identified SRF activity as one of the major transcription factors whose activity is increased.
In the second part of this thesis we analyzed how one bout of exercise can influence histone modification and modify the epigenetic landscape, possibly leading to an increase in SRF-dependent activity.
Growing evidence indicates that chromatin remodelling is one of the most important mechanisms that might influence gene expression. Post-translational modifications occurring on histones is emerging as a primary event contributing to the dynamic process of chromatin remodelling. We focused our attention on identifying histone marks, which have been linked to gene transcription, i.e. H3-K4me3, H3-K9K14ac and H3S10ph. We have examined the effect of an acute bout of high-intensity exercise (eccentric contractions) on these histone modifications in mouse skeletal muscle. We have found that histone 3 is very rapidly phosphorylated at serine 10 (H3S10ph) after eccentric contractions, which is completely absent in normal muscles and in the controlateral non-stimulated muscles. Immunofluorescence co-staining for dystrophin showed that this change occurs in about 40% of myonuclei. We have also found that this histone phosphorylation is followed by an increase in the acetylation of the nearby lysine 14, suggestive of an activation of gene transcription.
Next we worked on the identification of the putative kinases involved. It has been shown by other groups that the mitogen-activated protein kinase (MAPK) family is involved in H3S10 phosphorylation. We observed an increase in p38-MSK1 phosphorylation in exercised muscle compared to the control ones. In numerous mammalian cells, the mitogen- and stress-activated protein kinases (MSK1/2) have been identified as the kinases responsible for H3S10ph. Using a siRNA against MSK1 we found that MSK1 is required for H3S10ph after eccentric contractions in skeletal muscle. Indeed we completely abolished nuclear histone 3 staining in fibers electroporated with the siRNA, compared with the surrounding non transfected fibers.
We have started to analyse whether histone phosphorylation plays a role in exercise-induced gene expression and to address this we performed chromatin immunoprecipitation (ChIP) and quantitative polymerase chain reaction (real time PCR). Preliminary results show a marked phosphorylation on the promotor of p21, c-fos, Pgc-1α1 and Pgc-1α4 and a consequent expression of these genes. We are currently working on setting up the Chip-seq in order to generate high-resolution maps for the genome-wide distribution of H3S10ph.
In addition to our results in mice, we have studied human biopsies taken immediately after high intensity exercise and we have observed similar changes in signaling and histone phosphorylation.
In conclusion, we report two early signaling events which occur after high intensity exercise, namely an increase in MRTF-B-SRF dependent gene transcription and histone remodeling linked to gene activation
Endoplasmic reticulum oxidative stress triggers tgf-beta-dependent muscle dysfunction by accelerating ascorbic acid turnover
No full text: Endoplasmic reticulum (ER) and oxidative stress are two related phenomena that have important metabolic consequences. As many skeletal muscle diseases are triggered by oxidative stress, we explored the chain of events linking a hyperoxidized ER (which causes ER and oxidative stress) with skeletal muscle dysfunction. An unbiased exon expression array showed that the combined genetic modulation of the two master ER redox proteins, selenoprotein N (SEPN1) and endoplasmic oxidoreductin 1 (ERO1), led to an SEPN1-related myopathic phenotype due to excessive signalling of transforming growth factor (TGF)-beta. The increased TGF-beta activity in the genetic mutants was caused by accelerated turnover of the ER localized (anti-oxidant) ascorbic acid that affected collagen deposition in the extracellular matrix. In a mouse mutant of SEPN1, which is dependent on exogenous ascorbic acid, a limited intake of ascorbic acid revealed a myopathic phenotype as a consequence of an altered TGF-beta signalling. Indeed, systemic antagonism of TGF-beta re-established skeletal muscle function in SEPN1 mutant mice. In conclusion, this study sheds new light on the molecular mechanism of SEPN1-related myopathies and indicates that the TGF-beta/ERO1/ascorbic acid axis offers potential for their treatment
"The love that made hell, paradise." Ouida re-writing the Paolo and Francesca theme in Held in Bondage
No full textThe bestselling Victorian author Ouida reveals in her novels, and, in particular, Held in Bondage, an extraordinary knowledge od Dante, by using characters and themes from the Commedia. The Paolo and Francesca theme actually constitutes part of the plot of the novel and is to be found in many of her other works, short stories and non-fiction writing
HERStory Makers 2023: Francesca Fotheringham
No full textFrancesca Fotheringham is a postdoctoral research associate at the University of Edinburgh studying educational psychology with a focus on neurodiversity. She took part in HERStory Makers 2023.What is HERStory Makers?HERStory Makers is a social media competition for female-identifying early career researchers to share their research, their career journeys, and to inspire the next generation. Winners are selected by public vote. HERStory Makers is also part of EXPLORATHON, Scotland's contribution to European Researchers' Night.In 2022-23, EXPLORATHON Francescasupported by the Engineering & Physical Sciences Research Council [grant number EP/X020762/1].Author contributions to contentFrancesca conceived, planned, and recorded the video content. Kirsty Ross edited the video content to insert HERStory Maker credits, added subtitles, and reduce video length to below Twitter/X limit of 2 mins and 20 secs.</p
Medicina illuminata. La Biblioteca Lancisiana di Roma
No full textL'articolo presenta i codici miniati della Biblioteca Lancisiana di Roma. La prima parte, del coautore, è dedicata alla Biblioteca. La seconda parte, di F. Manzari, tratta dei manoscritti miniati, costituiti da due codici con le opere di Avicenna e dal Liber fraternitatis della Confraternita dell'Ospedale di Santo Spirito in Sassia a Roma.The article introduces the illuminated manuscripts of the Biblioteca Lancisiana in Rome. The first part of the article, by the co-author, is dedicated to the Library. The second part, by Francesca Manzari, illustrates the manuscipts; these are two manuscripts with the works of Avicenna and the Liber fraternitatis of the Confraternity of the Hospital of Santo Spirito in Sassia in Rome
A DH-Leavened Musicological Toolbox
No full textGraduate-level training in music research methodologies tends to ignore digital humanities work and overlook the use of digital tools created in support of new forms of reading. Training instead focuses on source material in the student’s area of interest. This material includes secondary and primary (archival) resources, as well as information resources, such as: monuments of music and critical editions; indexes; bibliographies and thematic catalogs; dictionaries and encyclopedias; digital libraries of scores or editions; and databases of period-specific newspapers or journals. Graduate students taking research methods courses already have a toolbox built from their experiences as musicians and students of music, including the ability to read and interpret music notation, to understand theoretical and analytical concepts in music, as well as a command of music history, including the canon of musical works.
Digital humanities has become a major area of academic endeavor at the “interface of technological development, epistemological change and methodological concerns." An important characteristic of digital humanities research has been its interdisciplinarity. We argue that graduate training in musicology needs to include coverage of methodologies applied by digital humanists in support of new forms of reading, not only to broaden the canon of research topics in musicology, but also to build common ground with researchers of other disciplines. We propose that librarians are well positioned to provide this expertise and training
A Twitter Case Study for Assessing Digital Sound
No full textAcademic and cultural heritage institutions around the world have made measurable strides in the development of digital sound archives oriented towards research and access, but their impact on scholarship and society has been little studied. Traditionally, impact has been measured by citations; yet these are problematic metrics for non-traditional outputs like sound recordings. Social media data provide a promising avenue of investigation for measuring scholarly as well as societal impact. Twitter in particular has been shown to provide a high number of references for cultural and research outputs in all disciplines. This study analyzes Twitter references pertaining to the collections of five digital sound archives: British Library Sounds, Europeana Sounds, the Internet Archive Audio Archive, PennSound and UbuWeb. Using text analysis methods to identify high frequency events and trends, and labeling them with a rubric designed for measuring the impact of digital heritage resources, this study provides preliminary insights on user values as they relate to digital sound collections. Despite the limitations of using social media data, the evidence gathered in this case study characterizes aspects of the use of digital sound collections, and may point to future priorities for the digital preservation of sound.Peer reviewe
Against the Grain: Reading for the Challenges of Collaborative DH Pedagogy
No full textThis article provides a critical review of the past five years of literature in digital humanities pedagogy and faculty-librarian collaboration, commingled with reflections on personal practice, which extend findings from the literature. Faculty-librarian partnerships in DH pedagogy reflect a rapidly evolving area of engagement calling for expertise in teaching, subject knowledge, scholarly communication, digital technologies, and DH research methodologies. Although there is a rapidly expanding body of literature on these partnerships, the challenges of the work tend to be minimized. This article expands upon commonly encountered difficulties, and it points to potential solutions and best practices.Peer reviewe
SoundCloud
No full textCan't get a clear policy on OA from Notes. Hoping an AM is okay. I can email Notes staff, if helpful
Le differenti gioventù del '68, in: Uguaglianze/differenze. Riflessioni per Anna Rossi-Doria
No full textIn questo articolo l’A. riassume i punti essenziali della sua ipotesi interpretativa a proposito della “generazione del 68”.
Convinta della necessità di decostruire questa categoria, Francesca Socrate si propone di analizzare il profilo sociale e culturale delle studentesse e degli studenti universitari che fecero parte del movimento focalizzando l’attenzione in primo luogo sulla loro età, per arrivare alla definizione di almeno due “generazioni sociali” che, per quanto separate da una ridotta distanza anagrafica, portano i segni di due culture tra loro distanti: la prima è quella dei nati durante gli anni della guerra; la seconda, quella dei nati tra il ‘46 e il ’51. Alla prima coorte generazionale appartengono la maggior parte dei leader del movimento studentesco, alla seconda ragazzi e ragazze più giovani che sono presenti nel movimento, spesso con un’alta intensità di partecipazione, ma in una posizione gregaria. L’A. mette in rilievo come questo rapporto sia nella sostanza solo apparente, dal momento che nell’intreccio fra le due componenti generazionali saranno i più giovani a imporre la loro cultura generazionale, non tanto nelle sue teorizzazioni ma nelle pratiche, mentre le parole, le parole chiave e le parole d’ordine, saranno trovate dalla prima generazione, quella dei nati durante gli anni della guerra.The Diverse Youth Groups of '68
In this paper, the author summarises the main points of her interpretative hypothesis regarding the "'68 generation".
A conviction of the need to deconstruct this category prompted Francesca Socrates to attempt an analysis of the social and cultural profiles of the male and female university students who were part of the movement, focusing principally upon their age in order to define at least two "social generations" which, though separated by only a few years, bear the marks of two widely divergent cultures: the first is that of those born during the Second World War, and the second that of those born between 1946 and 1951. The first generational group contained most of the leaders of the student movement, while the second contained younger people whose role in the movement, though often highly active, was principally that of adherents. The author highlights how this apparent relationship is essentially superficial, since in the interweaving of the two components it was the younger generation who would impose their generational culture, less in theoretical than in practical terms, while the words, the catchphrases and slogans would derive from the first generation, those born during the war years.
Keywords: generations; 19698; youth culture
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