University of Sassari

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    9009 research outputs found

    Immune response against <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i>, Epstein-Barr virus, HERV-K and IRF5 in rheumatoid arthritis

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    Rheumatoid arthritis (RA) is an inflammatory disease characterized by synovitis, systemic inflammation, autoantibodies that causes joint damage, disability, decreased quality of life, and cardiovascular and other comorbidities. Its aetiology as well the exact etiopathogenetic mechanisms are not well clear so far. RA is triggered by an interplay between genes and environmental factors. Several studies showed that microorganisms play an important role in triggering autoimmunity through different mechanisms of action. Viral and bacterial infections, such as those caused by Epstein-Barr virus (EBV), Human Endogenous Retrovirus (HERVs) and mycobacteria, may play a pathogenetic role in RA through immunological cross-reactivity or molecular mimicry. Sardinians have a peculiar genetic background resulting from a long lasting geographical isolation with a strong incidence and prevalence of different autoimmune disease such as RA, multiple sclerosis (MS) and diabetes. During this PhD course, I have studied the role of EBV, HERV-K and Mycobacterium avium subsp. paratuberculosis (MAP) in RA pathogenesis and other rheumatic diseases for a better understanding of how these infectious agents can lead to a deregulation of transcription factors such as Interferon Regulatory Factor 5 (IRF5) that is important in the regulation of different cells type like macrophages and neutrophils. Finally, in order to better understand the etiopathogenesis of RA, an animal model has been used to study the molecular mechanisms involved in the above-mentioned diseases and to better understand the link between the environment and genes in RA with an objective to develop new therapeutic strategies

    La Pianificazione in zone di conflitto: il caso di Gerico nei Territori Palestinesi occupati

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    In the Israeli-Palestinian context there is an intricate territorial conflict based on two different and contrasting narratives of historical, cultural and religious belonging. In this clash, it is the state of Israel that holds power and exercises it through spatial, politicaladministrative and economic control over the Occupied Palestinian Territories. Since 1948 a continuous process of contraction of Palestinian Territories (PT) has been initiated, this by means of targeted policies such as the incessant construction of Israeli settlements, the declaration of military zones and the construction of by Pass roads etc. The research explores and analyzes the role that planning has played in the process of colonization of the PT, using planning techniques to achieve political objectives, by making the strong part prevails against the weaker one. Thus, this thesis aims, from one hand to demonstrate the ineffectiveness of planning system used by the Palestinian National Authority in areas of its sovereignty: it is done through the use of analytical and comparative methodology to study the planning system in the PT and its historical development and the descriptive method of the impacts of Israeli policy on Palestinian cities. From the other hand, by using the city of Jericho as a case study, the thesis elaborates the research issues and advices for better planning and management of the PT based on future scenarios of the political situation

    Cystic echinococcosis in cattle: histological and proteomic features of inflammation

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    Cystic echinococcosis (CE) is caused by the larval stage of Echinococcus granulosus and is a widespread zoonotic disease. The World Health Organization (WHO) included CE in the list of Neglected Tropical Diseases in order to eliminate the disease and support the affected countries. The aim of the study was to compare fertile and infertile cysts from naturally infected cattle by means of histological and proteomic analysis in order to elucidate the molecular cross-talk between host and parasite and obtain further information on the bovine host immune response against E. granulosus. In this study, 70 hydatid cysts were removed from parasitized bovine lungs and livers. Each cyst was ranked as fertile or infertile and processed through histologic, immuno-histochemical, biomolecular, and statistical analysis. After that, 27 pulmonary tissues and 10 hydatid fluid samples were analysed with a Tandem Mass Tag (TMT)-based quantitative proteomics approach. As a result, four degrees of inflammation were detected, and thousands of proteins were identified in both tissues and fluids. Based on ontology and pathway analysis, several differential proteins are involved in the modulation or activation of host defence mechanisms. In conclusion, the combination of histological and proteomic approaches applied in this work provided a better understanding of the host-parasite interplay and of the bovine host immune response against E. granulosus

    Target identification of small molecules with antiproliferative properties

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    1,3,4-oxadiazole derivatives are widely used in the research of antineoplastic drugs. On the basis of previous work, 16 new 1,3,4-oxadiazole compounds with different structural types were designed and synthesized on the basis of 2j, in order to obtain new efficacious anticancer with low toxicity and side effects. In the present research, the results showed that 7FB, 16FB, 8VDB, 22VDB, and 23VDB had a significant inhibitory effect on tumor cell lines and caused cell cycle arrest at G2/M phase in a time-dependent manner in Hela and PC-3 cells. In order to further study 2j and its derivatives possible targets and identify molecular mechanisms, the DEGs were determined after 2j, 16FB and 8VDB treatment. RNA-seq was performed and data were analyzed using functional (GO term) and pathway (KEGG) enrichment of the differentially expressed genes (DEGs). The hub genes of anti-tumor small molecules were determined by the analysis of protein-protein interaction networks. The results showed that 2j and its derivatives were tubulin inhibitors, mainly affected tumor cells through the cell cycle, FoxO signaling pathway, and apoptotic and p53 signaling pathways. Based on STRING analysis of function gene networks, hub genes were identified and the small molecular targets obtained by CMap comparison, the possible targets of 2j, 16FB and 8VDB could be TUBA1A, TUBA4A, and TUBB. Molecular docking results indicated that 2j interacted at the colchicine-binding site on tubulin

    Exploring stem cell fate from adipose tissue: novel approaches to modulate stem cell signatures

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    Stem cells (SCs), undifferentiated elements able to acquire specific phenotype upon stimulation, represent an important source for regenerative medicine, restoring function of compromised organs. The purpose of regenerative biology is to identify the cellular and molecular differences that distinguish normal tissue turnover from scar repair, in order to create an ideal microenvironment suitable for regeneration in damaged adult tissues. Stem cell differentiation is a complex process controlled by signaling pathways and molecular mechanisms, acting to maintain tissue homeostasis. A wide range of natural molecules and compounds, known as nutraceuticals or functional foods, are widely used for their therapeutic or preventive effects. These natural and synthetic molecules exert their action via epigenetic modulations of a specific molecular differentiation program and gene expression of lineage-specific markers. Within this context, unraveling the cellular mechanisms involved in the activation and differentiation of the adipose resident stem cells, could help in identifying innovative and preventive tools to counteract obesity and its related diseases. The aim of this project was to evaluate cell behavior in the presence of conditioned media, drugs or natural molecules, in the attempt to counteract the molecular mechanisms involved in inflammatory-associated adipogenesis. Understanding the molecular mechanisms involved in the decision of this fate could lead to the development of drugs capable of influencing stem cell behavior, for future in vivo clinical applications

    La Parola è il castello: critica della produzione spuria di Gesualdo Bufalino

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    This research work focuses on the spurious production (essays, comments, but above all elzevirs) of Gesualdo Bufalino's work. That is, on that part of the Sicilian author's writings that the official criticism is only now beginning to take an interest in. With this kind of approach it became possible to break down the biographical story of the writer from Comiso into the elements of his childhood, youth and old age: determining the seasons of his life, his afflictions and faults, if any. It also allowed us to read his opus of novels and poems with a different attention, offering us cues and insights that have opened up new and unexpected paths of study. By revealing, so to speak, the most sinewy and secret areas of Bufalino's pages, this approach has revealed an author with multiple interests. A man who not only dealt with books, but also with painting, music, photography and cinema, with all the most important forms of communication in the modern world. Therefore, Bufalino's elzevirist experience has become an inexhaustible mine of revelations, confessions and intertextual references, and in doing so, contributing, in a decisive way, to the understanding of the entire Corpus of the works of an author we thought by now canonized, and thus allowing a new and positive critical balance

    Von der Kritik zur Verteidigung der modernen Rationalität. Ein Vergleich zwischen den Geschichtsmodellen von Blumenberg und Foucault im Ausgang von Nietzsche.

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    The subject of this dissertation is a comparison between the historical approaches of Hans Blumenberg and Michel Foucault, in order to demonstrate a similarity between the philosophical paths of the two Autors: from the critic of the modern rationality to its defense. For this purpose the development of their historical thought is interpreted as gradual distancing from Heidegger’s History of Being with her critic of the modern age and as convergence to Nietzsche’s Standpoint on history in his so called middle period, to which corresponds a re-re-evaluation of the Enlightenment and of the modern science in comparison to his early works. The thesis is divided in four chapters. The first one examines the early work of Nietzsche, Foucault and Blumenberg, which criticized the modern rationality as impoverishment of an original human experience of reality. The second chapter focuses on Nietzsche’s Critique to the nineteenth-century historicism as well as on those one of Foucault und Blumenberg. The third chapter compared Blumenberg’s and Foucault’s early historical Models with Heidegger’s History of Being in order to show a similarity between them, in particular as regards the absence of the human subject in their historical considerations. The fourth chapter investigate the development of such models by Blumenberg and Foucault and their reevaluation of the role of the human actors, which lead them to a commitment to the Enlightenment

    Applicazione di nuove tecnologie per il monitoraggio di ambienti marino-costieri

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    In my PhD project, two low cost detection systems have been tested: a marine one to acquire high resolution data in the bathymetric range between 0 and -10m and, a terrestrial to acquire high resolution data on the beaches. High resolution Side Scan Sonar data acquisition strategies have been developed in shallow water (-5 and -2.5m), capable of communicate integrating data acquired with non-oceanographic systems (Georadar “G.P.R.”). These integrations allowed us to study the emerged shallow and deep submerged areas, and to create very detailed cartographies of the seabed of the Alghero bay, of the Bay of Porto Conte (De Luca et al., 2018) and of the some areas of the Asinara island. In addition to the Side Scan Sonar and the Remote Operated Vehicle (ROV), the classic satellite detection systems have been used as well as high resolution images acquired with drones (UAVs). This latest technology, simple to use and very cheap, allows the creation of aerial photographs of marine areas close to the coast, where the oceanographic instruments, at the moment are unable to acquire data (depth less than 2.5 m). The information acquired made possible to evaluate the state of the Posidonia oceanica seagrass, the coastal dynamics present in the Alghero harbour and to characterize two temporary storage sites used for the accumulation of the banquettes of Posidonia oceanica. The coast of Alghero has a unique peculiarity in Sardinian realm, that is; the accumulations of Posidonia leaves. These per year are about 3000 m3, mostly concentrated in the beaches of San Giovanni, Maria Pia and Punta Negra. The large accumulations of leaves are a problem for the recreational use of the beach. The formed banquettes can frequently reach one meter in height, occasionally exceeding two meters. Currently Posidonia oceanica (both leaves and banquettes) is moved by tractors and stored in temporary accumulation sites located near the beaches. For this reason, an action plan was prepared for the dismantling of the temporary storage sites of San Giovanni and Villa Segni. This was aimed to recover as much sand as possible the beach. The Ground Penetrating Radar (G.P.R.) was used to obtain information on the subsurface deposits in the San Giovanni are, to better correct management of the Posidonia accumulated leaves. The area has a surface layer composed of 10 to 50 cm of Posidonia residues mixed with sand, overlying about 3 meters of sand. Between the layers, some wastes with an expiry date or production date were found, useful for stratigraphic dating. These analyses allowed us to establish that the temporary storage areas are not a dump sites and that an accurate managing of them could reclaim sand to the beaches

    La Circolazione dei beni culturali: profili giuridici e sociali

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    Cultural goods are a peculiar kind of assets within the context of the Italian legal system. Indeed, despite they are capable of economic assessment, the economic aspect is prevalently scaled down in favour of a greater emphasis on their social function. They are an identifying feature of the Nation and a unique mean of human and intellectual enrichment. Hence, legal requirements for the transfer of such goods are strictly regulated, both within Italy and the European Union, in order to protect them and to ensure their proper preservation and use by the community. The State and the public authorities play a leading role in protecting, preserving and enhancing state-owned cultural goods and in governing the transfer of privately owned cultural goods with the aim of ensuring their protection. There has been plenty of activities aimed at finding new ways to raise up the value and social importance of cultural heritage; the role of private individuals has thus become significant, thanks also to measures such as the introduction of tax credit measures in this field (the so-called Artbonus) and sponsorships. As of today, although the Parliament has not yet discussed the possibility to grant cultural heritage with the status of “common heritage”, several proposals for a new approach to the management of cultural heritage and cultural goods have already came up. Worth to say, such proposals also provide for a closer engagement of the communities in such respect

    Genetic and technological characterization of indigenous Saccharomyces cerevisiae strains isolated from 'Merwah' wine (Lebanon)

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    In order to gain deeper knowledge of genetic diversity and population structure of Lebanese indigenous Saccharomyces cerevisiae strains, 202 isolates were collected during spontaneous alcoholic fermentation of eight must/wine samples of ‘Merwah’, native cultivar, over two consecutive years in a traditional winery in Mount Lebanon. The isolates were identified as belonging to the S. cerevisiae species based on their morphology and preliminary analysis of the ITS 1-4 region sequence. They were then characterized at strain level by analysis of the interdelta regions, and genotyped using 12 microsatellite markers. In addition, strains were subjected to test phenotypic sulfite resistance and chromosomal translocation on SSU1gene by means of PCR. To select the most potential yeast starter strains, micro-fermentations were carried out for 22 S. cerevisiae strains that were selected as representatives of the population. Based on the main technological parameters (i.e., residual sugar, fermentative vigour, lowest sulphur production and acetic acid), three yeast strains were selected as candidates for pilot-scale fermentation at the winery. These strains were subjected to chemical and sensorial analysis for selecting a S. cerevisiae strain, adequate to produce ‘Merwah’ wine. This study will devote to test the drying attitude of the selected strain; make industrial wine using the selected dry strain ad a starter; and verify the quality of the resulting wine

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