1,720,993 research outputs found
DNA damage promotes HDAC4 nuclear localization and G2/M promoters repression via p53 C-terminal lysisnes
No full textRepression of G2/M promoters after DNA-damage is an active mechanism that requires the p53 tumor suppressor. We have recently found that HDAC4 is recruited on NF-Y-dependent repressed promoters. In this report, we describe the relationship between p53 and HDAC4 recruitment following DNA-damage. (i) HDAC4 shuttles from the cytoplasm into the nucleus following DNA-damage, independently of the activation of p53. (ii) HDAC4 becomes associated to promoters through a p53-dependent mechanism. (iii) The C-terminal Lysines of p53, which are acetylated and methylated, are required for HDAC4 recruitment and transcriptional repression. (iv) TSA treatment, but not HDAC4 functional inactivation, relieves the Adriamycin-mediated repression of G2/M promoters. Our results indicate that HDAC4 is a component of the DNA-damage response, and that post-translational modifications of p53 are important for repression of G2/M genes
The transcription factor NF-Y is required for satellite stem cell proliferation and skeletal muscle tissue repair
No full textThe transcription factor NF-Y, composed by NF-YA, NF-YB and NF-YC subunits, has an important role in the regulation of cellular proliferation and differentiation in different cell types, among which muscle cells. While NF-YA, the DNA binding subunit of NF-Y, is down-regulated in the adult muscle of WT mice, its expression is observed in the mdx mouse, model for Duchenne Muscular Dystrophy, in which a massive regeneration mediated by resident muscle stem cells, namely Satellite Cells (SCs), occurs. With the aim to investigate the role of NF-YA in the SCs proliferation and differentiation, we generated and characterized a conditional knock out mouse model in which NF-YA is deleted in Pax7+ SCs by Tamoxifen induction in adult NF-YAflox/flox:Pax7CreER mice (NF-YA cKO). Cellular and molecular analysis carried out on isolated myofibers and SCs from WT and NF-YA cKO mice highlighted that NF-Y activity is important for the maintenance of SCs homeostasis. NF-YA loss depletes Pax7+ SCs pool and impairs SCs proliferation. Moreover, SCs-mediated regeneration following muscle damage induced by cardiotoxin is delayed in NF-YA cKO. The effect of NF-YA abrogation was also explored in post-natal muscle growth. Immunohistological analysis showed defects in muscle morphology and a decrease in SCs number in 3 weeks aged NF-YA cKO mice, period of major increment of muscle mass by SCs-mediated myonuclear accretion. The molecular mechanism underlying the impairment of SCs activity following NF-YA loss was investigated by AdenoCre-induced NF-YA deletion in ex vivo cultured SCs. Overall, our results highlight a role of NF-Y in muscle regeneration and in SCs fate, whose modulation could be useful to improve stem cell based therapies to treat muscular dystrophies
Role of the CCAAT-transcription factor NF-Y and its splice variants in myogenic differentiation and muscle regeneration
No full textThe expression of NF-YA, the DNA-binding subunit of the CCAAT-binding transcription factor NF-Y, is down-regulated in adult skeletal muscle to allow a complete terminal differentiation. The NF-YA gene encodes for two alternative splice variants, NF-YAs and NF-YAl: in human haematopoietic and mouse embryonic stem cells, the expression of NF-YAs or NF-YAl is crucial to promote proliferation or differentiation, respectively. The role of NF-YA isoforms in skeletal myogenesis and satellite cells fate has never been investigated. Here we show that both NF-YA isoforms are induced in mouse regenerating muscle and are expressed in satellite cells (SCs).
The abrogation of NF-Y activity impairs both proliferation and differentiation of SCs. Forced expression of NF-YAs stimulates SCs proliferation, while NF-YAl enhances their differentiation. The same effects are observed in mouse C2C12 myoblasts, in which the two isoforms activate opposite transcriptional programs.
NF-YAs upregulates genes annotated in growth factor binding, cell adhesion and extra cellular matrix Gene Onthology terms, while NF-YAl increases the transcription of genes belonging to sarcomere, muscle cell differentiation, development and muscle contraction categories. NF-YAl boosts myoblasts differentiation by up-regulating the transcription of novel NF-Y target genes, among which Mef2D, Six4 and Cdkn1C, which are known to be involved in the differentiation program. Overall, our results highlight the functional difference between NF-YA isoforms, whose modulation could be useful to improve stem cell based therapies to treat muscular dystrophy
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
DNA damage promotes histone deacetylase 4 nuclear localization and repression of G2/M promoters via p53 C-terminal lysines
Full text linkRepression of G2/M promoters after DNA damage is an active mechanism that requires the p53 tumor suppressor. We have recently found that histone deacetylase 4 (HDAC4) is recruited on NF-Y-dependent repressed promoters. In this report, we describe the relationship between p53 and HDAC4 recruitment following DNA damage using immunofluorescence, chromatin immunoprecipitation, and transfection experiments. HDAC4 shuttles from the cytoplasm into the nucleus, following DNA damage, independently of the activation of p53 and becomes associated with promoters through a p53-dependent mechanism. The C-terminal lysines of p53, which are acetylated and methylated, are required for HDAC4 recruitment and transcriptional repression. Trichostatin treatment, but not HDAC4 functional inactivation, relieves the adriamycin-mediated repression of G2/M promoters. Our results indicate that HDAC4 is a component of the DNA damage response and that post-translational modifications of p53 are important for repression of G2/M genes
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
Flexible Work Arrangement nelle grandi imprese italiane dopo il Covid-19
No full textUna delle tendenze più interessanti nel mondo del lavoro degli ultimi anni è stata la crescita della flexible work arrangement (FWA). Questa tendenza è dovuta principalmente a un duplice binario: da un lato, maggiore consapevolezza e sensibilità sui temi come l’equilibrio tra lavoro e vita personale, la gestione dello stress e il rapporto tra soddisfazione dei dipendenti e produttività; dall’altro, la pandemia da COVID-19 che ha innescato una rivoluzione e un riadattamento delle forme lavorative. L’obiettivo di questo paper è guardare al fenomeno emergente delle nuove forme di FWA da un punto di vista sociologico e organizzativo, con specifica attenzione rivolta alle imprese che manifestano un orientamento sostenibile, comunicato attraverso un sustainability report. Il paper costruisce la sua azione mediante l’analisi dei tre sustainability report prodotti da Barilla G. e R. Fratelli S.p.A, Salvatore Ferragamo S.p.A., rinominata nel settembre 2022 Ferragamo e NexumStp S.p.a. Lo studio studio dimostra la presenza di significativi fenomeni di spillover dei modelli d’influenza FWA verso i clienti dell’aziende prese in considerazione. Un ulteriore elemento di originalità riguarda l’utilizzo di una metodologia di ricerca, con specifico riferimento all’ OC che consente di coniugare analisi della letteratura del well-being aziendale e analisi documentale dei sustainability report
Sull’effettività del diritto di asilo in tempi di pandemia: l’analisi comparata dei regimi emergenziali in Italia e in Ungheria
No full textAppropriate 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
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