181 research outputs found
Pro-apoptotic role of AMP-activated protein kinase under oxidative conditions linked to bioenergetic impairment: implications for cancer treatment and neurodegeneration
No full textLo squilibrio tra produzione di ROS e loro eliminazione porta a stress ossidativo, una condizione implicata nella patogenesi di molti disordini cellulari come la neurodegenerazione e il cancro.
In questi constesti, condizioni pro-ossidanti attivano molte proteine redox-sensibili coinvolte nella regolazione del programma apoptotico. Tra di questi, p53 e le MAPK sono implicate nella patogenesi dei disordini neurodegenerativi e in molte strategie chemioterapeutiche finalizzate alla eliminazione di cellule cancerose dal pool replicativo. Recentemente AMPK è stata identificata come un componente della cascata di segnalazione capace di percepire stress bioenergetici e ossidativi. Inoltre la sua capacità di indurre apoptosi attivando p53 o taluni membri della famiglia delle MAPK (ad es. p38MAPK), la rende implicata sia nelle malattie neurodegnerative che nel trattamento del cancro. Sulla base di queste conoscenze, questa tesi di dottorato è finalizzata ad elucidare le prpoprietà pro-apoptotiche di AMPK nella linea neuronale SH-SY5Y in risposta a condizioni pro-ossidanti di AMPK associate a stress bioenergetico. La ricerca è stata realizzata usando 3 composti noti influenzare l'omeosatsi redox:Bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N’]copper(II) perchlorate (Cu(isaepy)2), tetrahydrobiopterin (BH4) and sodium nitroprusside (SNP).The imbalance between ROS production and clearance leads to oxidative stress, a condition implicated in the pathogenesis of several cell disorders such as neurodegeneration and cancer. In these settings, pro-oxidant conditions activate many redox-sensitive proteins involved in the regulation of the apoptotic program. Among them, the tumor suppressor p53 and the mitogen-activated protein kinases (MAPK) are implicated both in the pathogenesis of neurodegenerative disorders and in many chemotherapeutic strategies aimed to the elimination of cancer-prone cells from the replicative pool. Recently, AMP-activated protein kinase (AMPK) has been identified as a component of the signaling cascade able to sense bioenergetic and oxidative challenges. Moreover, its capability to trigger apoptosis by activating p53 or some members of the MAPK family (e.g. p38MAPK), makes it a putative player both in neurodegenerative disease and in cancer management.
On the basis of this knowledge, this PhD thesis is aimed to elucidate the pro-apoptotic properties of AMPK in SH-SY5Y neuronal cell line under pro-oxidant conditions associated to bioenergetic impairment. This research has been performed by using three compounds known to affect cellular redox homeostas: Bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N’]copper(II) perchlorate (Cu(isaepy)2), tetrahydrobiopterin (BH4) and sodium nitroprusside (SNP). Our experiments demonstrated that Cu(isaepy)2, by acting as a DLC-like molecule, was able to induce cell death by activating the AMPK/ p38MAPK/p53 signaling axis, in response to a mitochondrial impairment. The cross-talk between these proteins was found to be operative also in SH-SY5Y cell death induced by BH4, an obligatory cofactor for tyrosine hydroxylase in dopamine synthesis, and to be sensitive to the alteration of glycolytic metabolism. Finally the observation that the iron-nytrosil complex SNP was unable to affect cellular energetics, explains on the one hand the uneffectivenes of AMPK in mediating SNP-induced apoptosis and, on the other, suggests a possible role for this energy-responsive kinase in apoptosis engagement only under condition of bioenergetic stress
Pino Pizzigoni’s ‘Minima House’ in Bergamo: from the Architectural Project to Its Safeguarding
No full textThe ‘Casa Minima’ designed by Pino Pizzigoni in Bergamo (1946) is a life-size model of single-family housing. A component of a ‘side-by-side’ system that was planned to generate a popular district, which was ultimately not implemented. To respond to the construction crisis following the Second World War, the architect designed an architecture that was both singular and unique in space and volume. He proposed a new model that encompassed both the housing type and the cost and time savings associated with construction. A minimalist prototype capable of combining modern construction technologies and materials used for the traditional mountain retreats in the Orobic Alps and/or for Mediterranean dwellings in the heart of the Aegean Sea. This paper proposes a new reading of the building through a careful graphical analysis that has highlighted a geometric severity and a rigor of the proportions of each of its parts, even of the furnishings. The review of the archives (architectural drawings, photographs, and documents) was accompanied by a direct observation to uncover the differences between the project idea and the built. An in-depth investigation that underlined the transformations undertaken over the time, not always respectful of the identity of the edifice until the restoration work carried out in the 1990s by the architect’s son, Attilio Pizzigoni, who brought the ‘Casa Minima’ back to its original soul
The Tricarboxylic Acid Cycle at the Crossroad Between Cancer and Immunity
No full textSignificance: The tricarboxylic acid (TCA) cycle is a housekeeping metabolic pathway essential for generation of energy and biosynthetic intermediates. Alterations of the TCA cycle play a pivotal role in oncogenesis and inflammation. As such, some metabolic vulnerabilities, imposed by TCA cycle dysfunction in cancer, have been identified. Similarly, the TCA cycle appeared as an actionable pathway in immunopathologies. Recent Advances: Metabolic changes accompanying cell transformation have been usually considered as adaptive mechanisms to malignant transformation. The identification of oncogenic mutations in some TCA cycle enzymes changed this view, indicating altered mitochondrial metabolism as an instrumental mechanism for cancer initiation. Similarly, the observation that TCA cycle-derived metabolites have multiple signaling roles in immune cells supports the idea of this pathway as a metabolic rheostat of immune responses. Critical Issues: This review summarizes the crucial role of the TCA cycle in pathophysiology describing the post-translational and epigenetic impact of oncometabolites accumulation in cancer and immune cells. Future Directions: Additional studies will be necessary to further explore the role of oncometabolites in paracrine signaling and to identify genuine metabolic and nutritional liabilities imposed by TCA cycle dysfunction in cancer, hardly to be escaped by resistance mechanisms
TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State
No full textInborn defects of the tricarboxylic acid (TCA) cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology
Analisi comparative tra modelli 3D fotogrammetrici: dati RAW versus immagini RGB dopo il trattamento raw-conveter
No full textIl caso studio del Torresino da Polvere di via Beltrami, in città alta a Bergamo, ha fornito il pretesto per uno studio comparativo tra i modelli 3D generati dall’elaborazione diretta dei dati del sensore fotografico e quelli ottenuti dal processamento di immagini dopo i tradizionali trattamenti raw-converter. Interessanti considerazioni hanno evidenziato delle singolari peculiarità di alcuni software nella gestione del dato grezzo, sia per un’elevata accuratezza delle restituzioni, sia per un’inaspettata rapidità di calcolo
Desarrollo de software cliente de Sakai para sincronizar recursos automáticamente
No full text[ES] UniSync es una herramienta desarrollada para usuarios de la plataforma de e-learning
conocida como Sakai, permitiéndoles descargar recursos de los diferentes sitios del servidor y
sincronizarlos de forma automática, sin que el usuario tenga la necesidad de acceder al portal
web o de tener que realizar algún movimiento extra. Además, UniSync asegura que los usuarios
tengan sus recursos siempre actualizados, en caso de que el autor realice modificaciones.[EN] UniSync is a tool for users of the e-learning platform known as Sakai, allowing them to
download resources from the different sites on the server and synchronizing them automatically,
without having the need to access the web portal or having to perform some extra movement.
Furthermore, UniSync ensures users will always have their resources up to date, if the author
makes changes.Sañudo Cardaci, AD. (2014). Desarrollo de software cliente de Sakai para sincronizar recursos automáticamente. https://riunet.upv.es/handle/10251/48356.TFG
Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug
No full textThe Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings
Il priorato di Sant'Andrea extra placeam e i quattro mulini: ipotesi di riuso e valorizzazione di un simbolo identitario della città di Piazza Armerina
No full textA precious evidence from the medieval period, the Church of St. Andrew is a key element in the reconstruction of the genesis and evolution of Piazza Armerina, well-known for the Villa Romana del Casale but just as rich in cultural heritage. The building, located on the north-west outskirts of the city, was probably erected in the first half of XII century by Simone Aleramico, Count of Butera and then by him donated, along with four mills and other goods, to the military order of the Holy Sepulcher. The elongated rectangular structure with a transept and three apses is now all that remains of the Grand Priory; on the vestiges of what was almost certainly the cenoby, there is a small rural edifice built in the 40s of the last century and today semi-abandoned. The church, used for sporadic events, also appears physically and perceptually separated from the Gela river landscape to which was historically linked, because of the presence of an overpass. Seen as the starting point of a knowledge path of the old mills of the area, the project that this work intends to summarize proposes some hypotheses of reuse and valorization aimed at giving back to the whole territory, the identity values partially lost
Integrated survey methodologies for the knowledge, restoration and valorization of modern architecture. The case study of the Archaeological Museum of Siracusa designed by Franco Minissi
No full textThe knowledge of an articulate architectural organism cannot disregard its critical observation: it is important to detect what it generously shows but especially what it jealously hides. This twofold recognition allows making the essential breakthrough for the planning of a conscious restoration project that will so find on it, a solid support on which to unfold and develop. This identification is a multi-faceted process that can today take advantage of digital technologies. These instruments - if properly selected and managed - can facilitate an indepth investigation, stimulating new considerations and inspiring new fields to explore. In this framework, this paper describes the path followed in the study of a modern building: the Regional Archaeological Museum "Paolo Orsi" in Syracuse, designed by Franco Minissi in the '60s and opened to the public almost 30 years later. This work, based on a careful "reading" of the edifice and its environment, made by integrating archival and documentary analysis and different survey methods, aims at suggesting the proper interventions to conserve and enhance the design process developed by the author. It, also, intends to contribute to the definition of a new approach to the museum visitor experiences through multimedia. Conceived as a vital center for research and cultural promotion, the museum, thanks to virtual reality technologies, can today found new capabilities, although keeping its original spirit
Comparative analysis among photogrammetric 3D model: s RAW Data vs. RGB Images
No full textThe military architecture of the ancient Republic of Venice is a very significant heritage. These are structures with simple volumes in the building and functional in the distribution; they are often little considered because, wrongly, they are considered minor. The cultural capital that must be documented and digitized to preserve, improve and preserve. The case study of the “Torresino da Polvere” in via Beltrami, in the upper town of Bergamo, was used as a pretext for a comparative analysis between the 3D models. Models generated by the direct processing of data from photographic sensors and those obtained from image processing after conventional raw conversion processes. The research, based on rigorous experimentation, proposes a new method of capture and frame management in order to obtain high quality models directly from the raw data. The results allowed some interesting considerations; they highlighted the singular peculiarities of some software in the management of raw data, both for a higher accuracy of the returns, and for an unexpected speed of calculation
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