80 research outputs found

    Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex

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    The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes

    Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex.

    Get PDF
    The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes

    SAMMSON fosters cancer cell fitness by concertedly enhancing mitochondrial and cytosolic translation

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    Synchronization of mitochondrial and cytoplasmic translation rates is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translational uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, compensating mechanisms in mitochondrial translation remain elusive. Here we show that the malignant long non-coding RNA (lncRNA) SAMMSON promotes a balanced increase in ribosomal RNA (rRNA) maturation and protein synthesis in the cytosol and mitochondria by modulating the localization of CARF, an RNA-binding protein that sequesters the exo-ribonuclease XRN2 in the nucleoplasm, which under normal circumstances limits nucleolar rRNA maturation. SAMMSON interferes with XRN2 binding to CARF in the nucleus by favoring the formation of an aberrant cytoplasmic RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNAs. These data highlight how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct cellular compartments to promote cell growth

    Paradigm Shift - From "Tabula Rasa" to Care. A key note intervention

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    L'intervento dell'autore, invitato come "key note" ad introdurre una track del convegno internazionale di Europan '17 - La Ville Vivant, di Vienna, illustra una prospettiva strategica innovativa nel quadro dell'urbanistica contemporanea. Si concentra sul rapporto tra "cultura della tabula rasa" e strategie per la cura di territori, paesaggi e spazi urbani. Un excursus di ordine storico critico viene articolato con esempi, referenze e buone pratiche tratte da progetti contemporanei

    Le Paysage dans la «stadt von übermorgen». Enquête sur les nouveaux attributs de la notion de paysage dans les programmes de recherche-action pour la ville de l’après-demain en Allemagne.

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    La presentazione come relatore al convegno internazionale approfondisce il ruolo che la nozione di Paesaggio può giocare nello sviluppo di strategie di lungo termine a partire da esperienze condotte sul territorio Tedesco. L'intervento si articola in una prima parte, di ordine più teorico, improntanta all'analisi di letteratura urbanistica tedesca improntata allo studio e all'uso di strumenti di futurologia e scenario planning, e in una seconda parte, in cui si verificano alcune ipotesi di ricerca a partire dall'applicazione delle ipotesi di partenza su una ricerca condotta dall'autore sul territorio di Essen, nel quadro di esperienze di CO-design

    "Pensare la città-parco - esperienze Europee" - relatore al convegno inter-facoltà : MARCOVALDO - Nature in città. UNIFE - POLIMI - UNIFI - Ferrara DA

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    The conference presentation illustrates the notion of City-Park through modern history, giving an historical overview of this concept in different Planning traditions and paradigms. It also offers three points to think the city-park of tomorrow by navigating references under the framework of urban crisis

    KH STUDIO - Building Strong Stories - "Storie, Metodi, Visioni" - Conferenza LSFD - UNFE DA - Corso . Farinella

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    The conference presented three projects from the Paris-based practice for Urban and Landscape design KH STUDIO, illustrating design methodologies, actor relational planning processes, and landscape design projects. The conference focused on methods for Vision Making and strategic design for public municipalities in the German and French context in the framework of transition and sustainble development

    "Paesaggi Contemporanei : Profondità, Logistica, Cura" - Relatore al convegno internazionale Premio S. Bastelli 2023

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    L'intervento del relatore propone una riflessione sulle tematiche chiave per pensare il progetto del paesaggio contemporaneo. I temi della logistica degli alberi, della gestione del suolo come risorsa, e dell'attenzione al territorio come pratica di Cura vengono approfonditi illustrando dati che ne fondano la pertinenza, e referenze che illustrano potenziali percorsi progettuali

    Les paysages de la “stadt von übermorgen” (ville d’après-demain). Enquête sur les nouveaux attributs de la notion de paysage dans les programmes de recherche-action pour la ville de l’après-demain en Allemagne

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    Au cours des dernières décennies, nombreux ont été les tentatives de dépasser les limites conceptuelles et procédurales de la planification traditionnelle par le recours à des nouveaux méthodes d'imagination des futures relations entre l'homme - la ville - l'environnement. Il suffit de penser aux expériences de la "Prospective" française, de la « Futurologie » aux Etats-Unis, ou des « Ateliers Internationaux du Grand ... Paris, Genève, Luxembourg, tout comme des « Laboratoires de recherche par le projet » pour les territoires post-charbon de la Rhénanie et de la Lusace en Allemagne. Dans chacun de ces dispositifs d'anticipation la notion de Paysage incarne des rôles et des définitions différents par rapport au projet de Vision, offrant tour à tour un support rhétorique, des repères pour l'action, ou un objet de partage et de cadrage de l'espace collectif avec lequel identifier un terrain de changement. Cet article se concentre sur le contexte allemand et sur un nouveau courant d'études et de processus de "mise en vision" urbaine et spatiale, inspiré par les missions pour la ville de Uber-Morgen (après-demain), lancées par le gouvernement allemand (ministère BBSR - construction, affaires urbaines, développement spatial). Ces études inspirent et guident actuellement l'action de prospective de plusieurs villes allemandes dont Bochum, Aix-la-Chapelle et Essen, Köln, dans le cadre de l’action stratégique pour les centres-villes de demain. Pour l'étude de cas spécifiques, l’article fait appel à des enquêtes de terrain auprès de concepteurs et acteurs publics promoteurs des études analysées. L'article passe en revue la base théorique et les expériences passées qui alimentent le volet de la recherche-action. L'objectif est d'étudier les caractères émergents de la notion de paysage dans la "Uber-Morgen Stadt". Cela permet d'identifier les contraintes inertielles actuelles et les chocs futurs auxquels le "nouveau paysage" est appelé à répondre. Quelques questions directrices structurent les conclusions de l'article : le projet de paysage trouve-t-il une nouvelle primauté par rapport à la prééminence traditionnelle de l'environnement bâti, de la croissance et du développement, ou est-il une forme d'"avant-garde inoffensive" utile à la création de consensus ? La notion de paysage et ses politiques de mise en valeur s'élargissent-elles et s'hybrident-elles avec des politiques relevant d'autres agendas ou restent-elles dans le périmètre du décorum et du " vert dans la ville " ? Quelle relation spécifique émerge entre l'accès à la nature en ville et la dimension démocratique dans les processus de décision et d'orientation des politiques publiques ? L'enquête se concentrera sur les nouvelles relations systémiques dont le paysage est le protagoniste, en tant que vecteur d'une ville de la connaissance inclusive et intégrée. L’objectif est de rendre explicites les méthodes de vision-making et de co-design qui permettent à ces nouvelles dimensions du paysage d’émerger et de faire ville autrement
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