1,720,959 research outputs found
A POTENTIAL ROLE OF MEF2C IN THE MYOGENIC PROGRESSION BESIDE TERMINAL DIFFERENTIATION
No full textMEF2C belongs to the family of Myocyte Enhancer Factor 2 transcription factors, which activate the muscle-specific gene expression program. Its activity is finely modulated at several levels but some aspects of this regulation still remains uncharacterized; for example, MEF2C is already expressed in proliferating myoblasts, but it is transcriptionally silent unless the cells are stimulated to withdraw the cell cycle and differentiate. Phosphorylation of MEF2 factors at so-called Ser/Thr-Pro motifs can modulate protein function through the induction of conformational changes by the peptidyl–prolyl cis/trans isomerase Pin1. This regulatory mechanism is based on the physical interaction between Pin1 and the Ser98 and Ser110 phosphoacceptor sites located in the alternative spliced exon α1 of MEF2C. The MEF2C/Pin1 interaction results in the repression of MEF2C stability and transcriptional activity, inhibiting muscle differentiation.
We investigated the function of this regulatory mechanism in primary myogenic stem cells (SCs) combining the analysis of the dynamics of MEF2C phosphorylation with the study of the alternative splicing pattern.
We demonstrated that the conditions necessary for the interaction between MEF2C and Pin1 are satisfied exclusively in proliferating SCs, where:
Pin1 expression is upregulated
MEF2C isoform containing the exon α1 specifically appears in response to activation signals
MEF2C phosphorylation on the Pin1-binding sites occurs specifically in proliferating SCs
Indeed we showed that MEF2C and Pin1 can interact in the nuclei of C2C7 and SCs-derived myoblasts. Overall we provide evidence that this interaction not only would serve as a failsafe mechanism to keep silent the MEF2C-dependent transcription of muscle specific genes in proliferating SCs but we hypothesize that the expression of the MEF2Cα1 isoform phosphorylated on Ser98 and Ser110 and the interaction with Pin1 might actively contribute to promote SCs proliferation, allowing the expansion of the activated SCs pool and avoiding their premature differentiation
IL FATTORE DI TRASCRIZIONE MEF2C AI CROCEVIA TRA PROLIFERAZIONE, SVILUPPO E DIFFERENZIAMENTO MUSCOLARE
No full textIl principale interesse del laboratorio è lo studio della funzione della proteina MEF2C, un fattore di trascrizione abbondante nel tessuto muscolare scheletrico dove dirige il differenziamento terminale dei precursori miogenici (mioblasti). In specifico, ci occupiamo di definire i meccanismi che regolano la funzione di MEF2C nella progressione miogenica. Abbiamo identificato un meccanismo di repressione dell'attività di MEF2C nei mioblasti proliferanti che coinvolge la fosforilazione della proteina e la sua successiva interazione fosfo-specifica con l'enzima Pin1, una peptidil-prolil cis trans isomerasi che diminuisce la stabilità di MEF2C. Questo meccanismo repressivo è importante per inibire un differenziamento prematuro dei precursori miogenici che in tal modo possono amplificarsi. La repressione Pin1-dipendente di MEF2C è attiva sia nella linea cellulare miogenica C2C12 che in cellule satelliti, vale a dire mioblasti primari di muscolo adulto, responsabili dei meccanismi di rigenerazione in caso di danno muscolare. Ci proponiamo di valutare se questo meccanismo è alterato nella distrofia di Duchenne, dove è stata osservata una diminuita capacità proliferativa delle cellule satelliti. L'attività di MEF2C è anche regolata da meccanismi di splicing alternativo del corrispondente trascritto. Nel nostro laboratorio stiamo definendo le funzioni specifiche di due isoforme di splicing di MEF2C che si differenziano per la presenza di due esoni mutualmente esclusivi: esone alpha1 e alpha 2. I nostri dati preliminari indicano che le due varianti di splicing svolgono funzioni opposte nel corso della progressione miogenica, in particolare la variante alpha1 sembra essere importante nel controllare la progressione nel ciclo delle cellule muscolari mentre la variante alpha 2 sembra essenziale per la trascrizione muscolo-specifica. Infine abbiamo osservato che in Zebrafish, Danio rerio, Mef2c svolge un ruolo importante nel regolare lo sviluppo embrionale, specificamente nella determinazione dorso-ventrale dell'embrione, inoltre la sua attività viene modulata attraverso meccanismi di splicing anche in questo organismo
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
Proline Isomerase Pin1 represses terminal differentiation and Myocyte Enhancer Factor 2C function in Skeletal Muscle Cells
No full textMEF2 (myocyte enhancer factor 2) transcription factors (MEF2A-D) are highly expressed in skeletal muscle cells, they bind to a conserved AT rich DNA sequence through their N-ter MADS and MEF2 domains and activate transcription via their C-ter transcriptional activation domains (TAD), the functional domains of MEF2C are indicated in Figure 1. MEF2 proteins interact with members of the MyoD family of basic helix–loop–helix (bHLH) proteins to establish a unique transcriptional code for skeletal muscle gene activation. Recent studies have revealed multiple signaling systems that stimulate and inhibit myogenesis by altering MEF2 phosphorylation and its association with other transcriptional cofactors. We show that the Pin1 isomerase, which catalyzes the isomerization of phosphorylated Ser/Thr-Pro peptide bonds, interacts with phosphorylated MEF2C in muscle cells. This interaction requires two novel phospho-Ser-Pro motifs in MEF2C: Ser(98) and Ser(110), which are phosphorylated in vivo. Overexpression of Pin1 decreases MEF2C stability and activity and its ability to cooperate with MyoD to activate myogenesis. Furthermore Pin1 modulates the skeletal muscle differentiation program because down-regulation of Pin1 markedly promotes myogenic differentiation. We suggest that Pin1 is a novel regulator of MEF2C function and muscle differentiation, it is expressed in muscle cells and a significant proportion of Pin1 in myotubes but not in myoblasts is excluded from the nucleus. We observed a reduction of phosphorylation of the Ser(98) and Ser(110) Pin1 binding sites in differentiated myocytes. Based on these results we propose a model in which, in proliferating myoblasts, Pin1, upon binding to phosphorylated nuclear MEF2C, leads to decreased levels and transcriptional activity of MEF2C. Upon induction of terminal differentiation, to establish a full activity of MEF2 proteins, a reduced Pin1-MEF2C association is required, possibly due to the relegation of Pin1 to the cytoplasm and to a reduced level of phosphorylation of Ser98 and Ser110
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