5,161 research outputs found
The Italian Economy Seen from Abroad over 150 Years
Since it became a united country, Italy was looked at with keen eyes by foreign economists, economic historians and policy makers. They wanted to see whether it would be possible for the economy of a country which had in the XVII and XVIII century regressed to the role of agricultural raw material exporter after having been the premier site of European industry, trade and especially finance, in the Middle Ages and the Renaissance, to redress itself and join the industrial revolution making good use of its population and territory, which gave it the potential to be among the great powers of Europe. In this paper several instances of this are considered, focussing on foreign observers who concerned themselves with the Italian economy at different stages of its development. An attempt is made to see what influence their opinions had on Italian economic debate and Italian policy-making.Italy, Economic history
Rural Water Development in Sub-Saharan Africa: A Comparative Study between Uganda and Tanzania
Global transnational efforts to achieve the Millennium Development Goal of halving the world population lacking access to improved water supplies are failing to address sustainable development in sub-Saharan rural communities. These efforts have been driven largely by water governance strategies centered on the controversial principle that water is an economic good, and as such, the development of water services shall be left to the supply-demand mechanisms regulating commodities\u27 markets. Uganda and Tanzania have embraced these strategies to varying degrees and have made strikingly different progress in developing their rural water sector. Uganda has maintained a steady rate of improvement in rural water coverage, while Tanzania has not. This comparative study between Tanzania\u27s and Uganda\u27s water governance principles and development approaches combined qualitative analysis of semi-structured interviews and water policies with participant observation of two case studies. The results of the study suggest the success of Uganda\u27s approach to water governance stems from the government commitment to retaining its role of providing basic services for the poorest strata of the population, de facto guaranteeing the constitutional right to water for all citizens irrespective of their economic status
Functions of the prion protein in neurodegeneration: a closer look to tau - PrP interaction
Tau protein is involved in a number of distinct neurodegenerative disorders called tauopathies, which include one of the major leading causes of death in the world, Alzheimer\u2019s disease. Over the past years, many in vitro and in vivo studies helped elucidating the main events leading to the spreading of the pathology and brain degeneration; however, the detailed molecular mechanisms underlying each step are yet to be discovered. Intracellular tau aggregates diffuse in the brain following anatomic connections, and their spreading is the result of the combination of extracellular release, uptake and seeding of the endogenous protein in receiving cells. Many molecular partners mediating tau internalization have been identified, but many others are still elusive. In particular, it would be worth investigating if different neurodegeneration-related amyloids (i.e. tau, \uf061-synuclein, amyloid-\uf062) might share a common pathway mediating their toxicity and cell-to-cell spreading.
In this PhD thesis, we analysed the contribution of the cellular prion protein (PrPC) to the internalization of tau fibrils. We took advantage of the methodology extensively described in the literature to produce synthetic amyloids made of the truncated form of tau protein named K18, consisting only of the microtubule-binding domains of the protein. We compared the uptake of K18 fibrils in two mouse neuroblastoma cell lines: wild-type N2a cells and N2a cells that had been knocked-out for PrPC (N2a KO). Our results indicate that the number of internalized amyloids is higher in N2a cells expressing PrPC compared to their knocked-out counterpart, suggesting that the prion protein might be one of the many uptake mechanisms. Indeed, the absence of PrPC does not block completely the entrance of tau fibrils in the cytoplasm. This phenomenon is mediated by the binding between tau fibrils and the prion protein, and configures itself as a mutual interaction: while PrPC promotes a higher internalization of the amyloids, the presence of tau fibrils leads to an increase in the total levels of PrPC, which accumulates on the cell membrane. Although it is not yet clear if this effect is be tau-driven or a simple side-effect, it might be responsible for a more sustained internalization rate. Subsequently, we used monoclonal antibodies directed against the different domains of PrPC in order to evaluate their role in the uptake process. What we found is that both the targeting of the N-terminus and of the hydrophobic region negatively affect the internalization of tau K18 amyloids, while the globular domain does not seem to play a role, at least not in the specific region we considered.
As the prion protein exists also in the pathological conformation PrPSc, we analysed its interaction with K18 fibrils using prion-infected neuroblastoma cell lines (ScN2a). The exposition of ScN2a cells to K18 amyloids resulted in a strong decrease of the PK-resistant
PrP levels, independently of the type of replicating strain (RML or 22L prion strains). We hypothesize that K18 fibrils might bind either to PrPSc or, more probably, to PrPC and thus prevent prion replication. Indeed, neither macroautophagy nor lysosomes were found to be overactivated as a consequence of the treatment.
In conclusion, our findings point towards a role for PrPC in the regulation of the cell-to-cell transfer of tau amyloids. Additionally, this study focuses on the molecular mechanisms of the relationship between tau aggregates and the pathological PrPSc. The co-presence of tau and prion pathologies has a clinical relevance, as it is a common feature of a subgroup of prion disorders characterised by a longer disease course
Studio di un sistema di visione per la mappatura colorimetrica della Sindone di Torino
Internet: http://www.shroud.com/fanti4it.pd
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