1,720,973 research outputs found
Epigenetic methylations and their connections with metabolism
No full textMetabolic pathways play fundamental roles in several processes that regulate cell physiology and adaptation to environmental changes. Altered metabolic pathways predispose to several different pathologies ranging from diabetes to cancer. Specific transcriptional programs tightly regulate the enzymes involved in cell metabolism and dictate cell fate regulating the differentiation into specialized cell types that contribute to metabolic adaptation in higher organisms. For these reasons, it is of extreme importance to identify signaling pathways and transcription factors that positively and negatively regulate metabolism. Genomic organization allows a plethora of different strategies to regulate transcription. Importantly, large evidence suggests that the quality of diet and the caloric regimen can influence the epigenetic state of our genome and that certain metabolic pathways are also epigenetically controlled reveling a tight crosstalk between metabolism and epigenomes. Here we focus our attention on methylation-based epigenetic reactions, on how different metabolic pathways control these activities, and how these can influence metabolism. Altogether, the recent discoveries linking these apparent distant areas reveal that an exciting field of research is emerging
p38α, the β-catenin chromatin associated kinase, as promising target in colorectal cancer stem cells for personalized therapy
Full text linkColorectal cancer (CRC) is the third most frequent malignancy, but the second cause of death for tumor in the western population. Only 14% of patients with advanced and metastatic disease survive five years from diagnosis. Recently, it has been shown that tumor relapse and chemoresistance depend on a small population of cells, called cancer stem cells (CSCs). Current evidence indicates that the Wnt cascade is the main driver in controlling CSC fate; the key player in this pathway is β-catenin, a cytoplasmic protein whose stability is regulated by the so-called “destruction complex”. During carcinogenesis, the increasing amount of β-catenin resulting from APC inactivation translocates into the nucleus, causing the transcriptional activation of several mitogenic genes, including c-Myc. c-Myc is one of the most important factors involved in CRC initiation and progression; indeed, it functions as a link connecting malignancy with stemness. During colorectal carcinogenesis, c-Myc is maintained upregulated through β-catenin-mediated transcriptional activation and ERK-mediated post-translational stabilization. Our data showed that p38α, a kinase involved in CRC metabolism and survival, contributes to both mechanisms. Previous reports in other tissues provided evidence that Wnt3a can activate p38, and the p38 pathway feeds into the canonical Wnt/β-catenin pathway at least at the level of GSK3β. Our findings also highlighted that CRC cells and colorectal cancer stem cells (CRC-SCs) have higher levels of activated p38 than their normal counterparts, and experiments using kinase-specific inhibitors revealed that these cells are “addicted” to p38 activity. Importantly, we found that p38α co-immunoprecipitates with β-catenin in both normal and cancer cells; however, these proteins are confined to the cytoplasm in colonocytes, while they significantly occupy discrete nuclear regions in CRC cells, CRC-SCs, and in vivo models. These data were further corroborated by the inhibitory effect of p38α blockade on several β-catenin-responsive genes (i.e. c-Myc, cyclin D1/2, survivin, and others). This functional interaction was further characterized by chromatin immunoprecipitation experiments, which demonstrated that p38α is a chromatin-associated β-catenin kinase required for the transcriptional induction of several Wnt target genes, including c-Myc. Additionally, we demonstrated that p38α, like ERK, stabilizes c-Myc protein levels by preventing its ubiquitination. The finding that the phenotypes arising after APC loss in the intestine are fully dependent on c-Myc target gene expression suggests that c-Myc inhibition may be a good target for chemoprevention in CRC. These considerations underline the relevance of molecular profiling and preclinical investigation in order to achieve more efficient and accurate therapies. Indeed, our study identifies p38α as a promising therapeutic target acting directly on c-Myc and CRC-SCs, which are thought to be responsible for tumor proliferation, metastatic dissemination, and chemoresistance
Fine cantiere mai. Oltre il terremoto
No full textTemporaneità ed emergenza rappresentano l’espressione della logica resiliente sul possibile ripensamento dei valori che i manufatti e le opere post-emergenziali possono rivestire al termine del loro uso primario, dettato da urgenza e necessità.
La condizione incombente di crisi ambientale si sta configurando come contesto socio-tecnico in cui sperimentare e programmare strategie e soluzioni per fronteggiare le condizioni multi-emergenziali dei prossimi anni.
Gli scenari post-sisma che l’Italia ciclicamente fronteggia conducono ad una riflessione su questioni in cui gli aspetti tecnici si estendono agli aspetti socio-tecnici, sociali e relazionali di luoghi fragili.
Sono trattati i temi: Il contesto internazionale: l’emergenza come driver
d’innovazione; la mancanza di una politica nazionale per la riduzione del rischio. L’Aquila e Amatrice; L’impatto sociale del terremoto e la riattivazione del sistema territoriale; Possibili scenari di seconda vita: co-progettazione tra memoria sociale e istituzionale
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
La temporalità del capitale fisico nel post-sisma: riflessioni a partire dal caso aquilano
No full textVariations 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
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