1,720,980 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
Molecular and cellular networks driving neurogenic muscle atrophy
Full text linkDuring neurogenic muscle atrophy, the interruption of transmission of neurogenic signals to the muscle, caused by loss of neuromuscular junction (NMJ) integrity, leads to muscle atrophy, an event that causes loss of muscle functionality with the obvious deleterious outcomes. NMJs degeneration is a prominent aspect of denervation, aging, and some pathological conditions, such as Amyotrophic Lateral Sclerosis (ALS). The precise molecular mechanisms and roles of muscle-resident cells, during neurogenic muscle atrophy, remain largely unknown. Available evidence suggests that the effect on myofibers caused by neuron loss involves neighboring resident cells. Therefore, we analyzed the gene expression profiles at bulk and single-cell level of Itga7-expressing cells in muscle and revealed the existence of a subpopulation of muscle-resident glial cells, distinct from muscle satellite cells, that are selectively activated upon nerve injury. Upon nerve lesion, these cells expand and activate a neurotrophic program, that is turned off upon recovery of NMJ integrity. Moreover, in a mouse model of ALS, these muscle-resident glial cells increase during disease progression but exhibit impaired neurotrophic activity, suggesting that defective activation of glial cells could be implicated in ALS pathogenesis. Therefore, a better understanding of the cellular and molecular signaling pathways in muscle-resident cells during traumatic or pathological denervation is critical for developing better therapies against neurogenic muscle atrophy and degenerative diseases such as ALS
Interazione assone-glia: l'acetilcolina rilasciata lungo gli assoni regola il differenziamento delle cellule di Schwann verso il fenotipo mielinizzante.
No full textNel sistema nervoso, durante lo sviluppo e nell’adulto, l’interazione tra neuroni e cellule gliali e fra gli assoni in crescita e la glia mielinizzante favorisce, attraverso la produzione di specifici segnali, la modulazione della proliferazione, sopravvivenza e differenziamento di ambedue le popolazioni cellulari. Vari fattori di crescita (es.NRGs) sono stati identificati come principali modulatori di questa interazione, ma molteplici evidenze hanno indicato che anche i neurotrasmettitori (es. GABA, adenosina e ACh) possono avere un ruolo chiave in tale interazione. Negli ultimi anni la nostra attenzione si è focalizzata sul ruolo svolto dall’ACh nel modulare la crescita e il differenziamento delle cellule di Schwann, la popolazione gliale mielinizzante del SNP. Nostri precedenti dati avevano dimostrato che l’ACh, attraverso il recettore muscarinico M2, è in grado di indurre nelle cellule di Schwann, un blocco della progressione nel ciclo cellulare e una aumentata espressione delle proteine della mielina (P0, PMP22 e MBP). Per verificare se l’attivazione del recettore M2 fosse in grado di indirizzare le cellule di Schwann verso il fenotipo mielinizzante, abbiamo analizzato l’espressione di una serie di fattori responsabili della fase proliferativa e di quella differenziativa dopo attivazione del recettore M2. Cellule di Schwann, isolate dal nervo sciatico di ratti neonati (2 gg post-natale), sono state trattate in vitro con l’agonista del recettore M2, arecaidina. Analisi mediante real time PCR e western blot hanno dimostrato che fattori notoriamente coinvolti nella fase proliferativa vengono significativamente repressi (es. c-jun, NRG1/1, recettori erbB2, Notch-1, Jagged-1). Al contrario, l’espressione di fattori coinvolti nel differenziamento verso il fenotipo mielinizzante, è significativamente aumentata (Krox20/egr2; Sox-10, NRG1/3). Il trattamento con arecaidina inoltre induce un significativo cambiamento nella morfologia delle cellule che appaiono più appiattite e che sviluppano zone di adesione tra cellule adiacenti, come suggerito dalla ridistribuzione di molecole di adesione cellulare e dall’analisi al SEM. Ipotizzando che il segnale colinergico differenziante per le cellule di Schwann provenga dall’assone, allestendo colture di espianti di gangli spinali (DRG) in camere di Campenot, abbiamo dimostrato che l’ACh viene rilasciata sia nel compartimento in cui sono presenti i corpi cellulari dei neuroni, sia in quelli dove si trovano i neuriti in crescita. Inoltre abbiamo osservato che i neuroni sensoriali esprimono il mediatoforo, una proteina che risulta coinvolta nel rilascio non vescicolato dell’acetilcolina. In conclusione i nostri dati dimostrano che l’acetilcolina può essere rilasciata lungo gli assoni dei neuroni sensoriali probabilmente proprio attraverso un meccanismo di rilascio non vescicolare; questo rilascio consentirebbe alle adiacenti cellule di Schwann di rispondere allo stimolo colinergico con il blocco della proliferazione e l’attivazione della mielinizzazione, condizione necessaria per consentire la corretta formazione e conduzione di assoni di grosso calibro
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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