1,721,001 research outputs found
ABNORMALITIES IN CELL SIGNALING AND RED CELL PATHOLOGIES
No full textI globuli rossi sono cellule anucleate altamente specializzate nel trasporto dell’ossigeno e dell’anidride carbonica. La membrana plasmatica che li circonda svolge un ruolo essenziale per il corretto svolgimento della loro funzione ed è costituita da un doppio strato di fosfolipidi e colesterolo all’interno del quale sono immerse numerose proteine integrali di membrana, tra cui la banda 3 risulta essere la più abbondante. La banda 3, oltre a consentire lo scambio di ioni cloro con ioni bicarbonato attraverso la membrana, riveste un ruolo fondamentale nella connessione con il network di proteine citoscheletriche (come le alfa-beta spettrine) attraverso l’interazione con il complesso multiproteico dell’anchirina e il complesso multiproteico della banda 4.1. Tali interazioni conferiscono agli eritrociti caratteristiche univoche di plasticità e stabilità meccanica che ne garantiscono la permanenza all’interno della circolazione periferica.
In questo contesto le modificazioni post-traslazionali delle proteine, in risposta a molteplici stimoli cellulari, modulano rapidamente la loro funzione ed il loro stato conformazionale. Tra queste, la fosforilazione dei residui di tirosina (Tyr) o serina/treonina (Ser/Thr), finemente regolata da specifiche chinasi e fosfatasi, risulta essere cruciale in svariati processi cellulari, come ad esempio il controllo del volume cellulare, la stabilità meccanica della membrana o il trasporto di ioni attraverso di essa.
Lo scopo del presente progetto di ricerca è stato quello di analizzare i sistemi di trasduzione del segnale coinvolti nell’omeostasi eritrocitaria, con particolare attenzione a due modelli di globuli rossi patologici.
Nella prima parte della ricerca abbiamo valutato l’effetto della triplice terapia antivirale a base di interferone pegilato e ribavirina in combinazione con un inibitore di proteasi di prima generazione (Telaprevir o Boceprevir) sugli eritrociti di pazienti affetti da epatite C cronica. I risultati ottenuti dimostrano che la triplice terapia induce un’anemia sferocitica acquisita con un incremento della quota di beta adducina fosforilata. Ulteriori studi ci permetteranno di caratterizzare meglio il ruolo degli inibitori di proteasi sull’omeostasi cellulare, tenendo in considerazione che l’anemia è una delle maggiori limitazioni di questo approccio terapeutico.
Nella seconda parte del progetto di ricerca abbiamo analizzato gli eritrociti di un modello murino transgenico knock out per Fyn, una chinasi della famiglia delle Src, che presentano le caratteristiche tipiche dei globuli rossi di pazienti con deficit di G6PD (glucosio 6-fosfato deidrogenasi). I nostri risultati dimostrano che Fyn è coinvolta nell’attivazione della G6PD e nel corretto funzionamento dei sistemi antiossidanti all’interno dei globuli rossi, in particolare nel pathway G6PD/NADP/Tioredossina reduttasi in relazione alla rigenerazione della perossiredossina 2 (Prx2) sia in eritrociti murini che umani.Red blood cells (RBCs) are enucleated cells specialized in delivering oxygen to body tissues. RBC membrane organization, which is characterized by phospholipids and cholesterol bilayer, containing integral membrane proteins such as band 3 that links RBC membrane to the alpha-beta spectrin based cytoskeleton network through two multiprotein complexes. The ankyrin and band 4.1 multiprotein complexes bridge the membrane to the skeleton ensuring the dynamic changes and membrane mechanical stability required by the permanence of RBC in the peripheral circulation.
Post-translational modifications (PTMs), such as phosphorylation, might rapidly modulate protein conformational state and interactions with neighbor proteins. Changes in either tyrosine (Tyr) or serine/threonine (Ser/Thr) protein phosphorylation state, through modulation of kinases and/or phosphatases, are involved in membrane functions such as cell volume regulation, membrane mechanical stability or membrane ion transport function.
The aim of the present research work is to analyze signaling pathways involved in red cell proteostasis.
We studied two different models of diseased red cells:
1) Red cells from patients with chronic C hepatitis undergoing to triplice anti-viral therapy
2) Red cells from a mouse model genetically lacking Fyn, a tyrosine kinase of the Src family kinase, which recapitulate red cell features of G6PD deficient erythrocytes
Our results demonstrate that:
- Triplice therapy induced an acquired spherocytic like anemia with increased phosphorylation of beta-adducin, worsened by ineffective erythropoiesis due to possible toxic effect of triplice therapy on erythropoiesis.
- Fyn is involved in activation of G6PD.
Future studies will be design to further characterize:
- The role of protease inhibitors and red cell homeostasis since anemia is a major limitation of this therapeutic approach.
- The role of Fyn in G6PD/NADP/Thioredoxin reductase pathway towards Prx2 in both mouse and human red cells
Synthesis and characterization of nanostructured materials for Li-ion secondary batteries
No full textRechargeable lithium batteries have already revolutionized the market of portable electronic devices. Potentially, in the next future, they are going to become the technology of choice for the huge market of electric vehicles (EV), hybrid-electric vehicles (HEV), and plug-in hybrid-electric vehicles (PHEV), where low cost, low environmental impact, as well as high specific performance batteries are needed. Even so, intensive efforts are still under way to further improve this relatively young systems. Actually, for the next generation of rechargeable lithium-ion batteries, further breakthroughs, especially in modifying and improving already known materials, are essential. In this context, considering the challenges and expectations for the energy storage devices in the near future, the present Ph. D. thesis offers an overview of the most promising electrode material for secondary Li-ion cells. Several materials were developed and thoroughly investigated, from the synthesis to the structural-morphological characterization and the evaluation of their electrochemical performance. The introductory section of the thesis (chapters I to III) provides a brief survey of the necessary background in the field of Li-ion batteries and battery materials. Chapter IV focuses on the several characterization techniques and methods used to analyse the synthesized samples. The following three chapters (chapters V to VII) focuses on negative electrodes. Three different kinds of materials were taken into account, each of them presenting a different reaction mechanisms towards lithium. To overcome the specific problems related to each material different synthesis approaches were considered and structural-morphological aspects were modified to optimise the final electrochemical performance. The first material considered was titanium oxide (TiO2), able to intercalate lithium ions. TiO2 powder is employed in a wide range of application, thus a great number of publications are present in the literature on this subject. Aim of my work was to probe different syntheses and evaluate potential differences among them, both from structural-morphological and electrochemical point of view. Two different TiO2 polymorphs were synthesized by means of different synthesis strategies. TiO2-B, usually considered the most promising polymorph, was firstly prepared. Although it showed appreciable characteristics, the performances of prepared samples were only modest, with respect to the following samples prepared. Nanostructured anatase, the second TiO2 polymorph considered, was successfully prepared by three different synthesis techniques: an evaporation-induced self-assembly (EISA) process, a sol-gel synthesis and a hydrolytic process. When the synthetic processes was optimized, the electrochemical performances of all these anatase samples were found to be superior with respect to the previous TiO2-B. Despite of the different synthesis methods adopted, the obtained results were similar: Coulombic efficiency, cyclability and specific capacity were highly valuable, also at the highest value of current regime applied, that is 10C (i.e. 3350 mA g−1). Some results are particularly interesting in view of a possible practical application. Actually they join good overall performances with a synthesis procedure extremely quick and easy to perform: this is greatly appreciable bearing in mind the increasing attention to low cost and environment friendly materials. The second anode material considered was iron oxide (particularly, α-Fe2O3), that presents interesting features, such as abundance, low cost and environmental friendliness. Moreover, its theoretical specific capacity is extremely high, more than 1000 mAh g-1, compared to 370 mAh g-1 of graphite, the standard Li-ion battery anode. Its mechanism of reactivity towards lithium (conversion reaction) involves the formation and decomposition of Li2O, accompanying the reduction and oxidation of the metal. As these reactions are possible and reversible only if the material has nanometric dimensions/large interfacial surface, several nanostructured α-Fe2O3 samples were prepared by nanocasting strategy, using different kinds of mesoporous silica (i.e. SBA 15, MCM 41, MCM 48) as hard templates. The selected approach allowed to easily tune the characteristics of the final products. Indeed, opportunely selecting the template significant improvements in cycling stability were obtained. Another interesting path, that needs further in-depth examination, was the substitution of the traditional liquid electrolyte solution with a quasi-solid polymer electrolyte membrane. This new configuration demonstrated good cycling stability and capacity retention, directly related to the polymerization process used (i.e., UV photo-polymerisation) in which the polymeric network is directly formed in situ at the interface with the electrode film. The last material considered for application as anode was tin oxide (SnO2), able to alloy with lithium and deliver the interesting reversible theoretical specific capacity value of 780 mAh g-1. As for α-Fe2O3, its main issue is the cycling stability after prolonged cycling and two different strategies have been explored in order to overcome this problem: particle nano-structuration and use of a carbonaceous buffer matrix. The first path allowed to obtain an interesting material, with very high specific capacity and good overall cycling efficiency. However, the problem of cyclability was only minimized but not completely solved. On the contrary, the second approach demonstrated to be completely successful, as the cyclability problem was completely solved and the obtained material showed elevated and stable electrochemical performances and was able to undergo prolonged galvanostatic discharge/charge cycles. The last chapter of the thesis concerns on the development of a material for the positive electrode, that is lithium iron phosphate (LiFePO4). It has received great attention during the last years because of its low toxicity and low cost. Aim of my work was the optimisation of a previously developed synthetic route (i.e., mild hydrothermal process in the presence of an organic surfactant), in view of a possible practical application of the resulting material in commercial lithium-based batteries. The presence of the cationic surfactant CTAB confirmed to be a distinguishing feature of this synthesis. Actually, the most significant improvements were obtained modifying the physico-chemical properties of the CTAB water solution. In particular, the most significant results were obtained by the addition of a co-solvent during synthesis, which led to significant differences on the micellization process of the surfactant, thus resulting in marked differences on the structural-morphological characteristics and electrochemical performances of the resulting samples. Two most evident effects were evidenced and both were related to the use of the co-solvent: the drastic change in morphology and the improved characteristics of the carbon layer. The changed morphology enhanced the ionic conductivity of the material, due to the promotion of the growth of the electrochemical active crystalline faces of LiFePO4. In addition, the improved characteristics of the carbon layer led to an increase of the final electronic conductivity of the active material particles, as the carbon layer surrounding the particles presented higher homogeneity and degree of graphitization. When the choice of the reaction conditions was carefully controlled, the resulting material showed outstanding electrochemical results: the increased performance, particularly registered at extremely high discharge rates (even as high as 100C), led to the publication of an international patent in 2011. This confirmed the feasibility for this material to be commercially applied in several areas, the most important one being batteries conceived for automotive and transportatio
L'architettura del Ventennio ad Aosta: le prime esperienze in cemento armato e i problemi della conservazione
No full textCentrali idroelettriche in Valle d'Aosta negli anni del Regime; l'impiego del cemento armato tra ingegneria e architettura
No full textGeneration of Pancreatic Organoid-Derived Isografts
No full textThis protocol is a procedure for generating orthotopic isografts using mouse pancreatic cancer organoids. These isografts can be used to track the evolution of pancreatic ductal adenocarcinoma (PDA) from a preinvasive lesion to a metastatic disease and therefore represent a suitable model for identification of determinants of PDA progression. For complete details on the use and execution of this protocol, please refer to Boj et al. (2015) and Filippini et al. (2019)
Effetti dei cambiamenti climatici sul patrimonio architettonico del Novecento: riflessioni sulla tutela e sul restauro attraverso l'analisi di casi studio in Piemonte
No full textThe need to protect the cultural values of the architectural heritage, and the demands for conservation and conscious reuse, are increasingly coming up beside the challenges posed by environmental transition, and sustainable development goals. Innovative solutions and technical 'compromises' are often urgently needed to guarantee the integrity of the qualifying topics of historic buildings and – at the same time – satisfy the new issues imposed by the effects of climate change and claims for energy saving. The contribution investigates, through the experience of academic research and the institutional preservation activities of the Superintendence, the management of valuable 20th-century architecture concerning these challenges, by analysing the critical issues and the operative solutions - aimed at both conservation and energy efficiency - as well as the problematic synthesis between the two objectives. The essay examines Palazzo delle Poste and Casa del Mutilato in Alessandria, emblems of the Fascist Regime architecture and of the 20th-century urban transformation, thinking over the balancing of values that restoration works must nowadays reconcile. The two cases witness the fragility and vulnerability of contemporary heritage if submitted to ageing stress-test, showing the adopted solutions between conservative and improvement strategies, promoting anyhow the prevalence of public interest over the private’s, and systemic contribution to global challenges combined to the values traditionally supported by restoration theory
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
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