“L’écomusée n’est pas musée”. Gli ecomusei come laboratori produttori di cultura, territorio e relazione

In presenting a current project for the implementation of a Landscape Ecomuseum in the Palestinian village of Battir, in West bank, the article explores some aspects of the history and of the theoretical and methodological framework of ecomuseums as emerged within the French movement of the Nouvelle Muséographie from the 1960s, together with other forms of alternative museographical strategies. At the core of the movement – moved by the ambition of starting a process of democratisation of the museal institutions and functions – there were three main ideas: a new conception of heritage, enlarged to encompass all the expressions of human culture and the notions of territory, community and local identity; the need of dispersing the walls of the majority museum to diffuse it on the territory and in the community; a perspective on museums as active engines in the productive process of cultural and social capital, rather than displays of representative projects generated by extra-local hegemonic powers. In rapport to other forms of alternative museums, the ecomuseum, despite representing an intrinsically polymorphous and evolutive reality encompassing a variety of different experiences, is characterised for its central reference and attention to the local dimension, at the environmental, socio-cultural and anthropological level. Rooted in a given territory and designed and animated with the participation of its inhabitants, each ecomuseum is unique since based on the safeguarding and valorisation of a specific social and geographical milieu. In the context of Battir village, characterised by many outstanding traits at the historical, anthropological and landscape level but threatened by the disruptive effects of the Israeli occupation and an ongoing conflict, an ecomuseum of landscape constitutes an important virtuous opportunity for resisting to the destruction of the territory and of the community by promoting and protecting what can be considered a world heritage and a set of shared universal values. &nbsp

Il processo architettonico ed urbano come laboratorio cooperativo di sostenibilità. Il caso della città di Constantine (Algeria)

Le distorsioni ambientali e socio-economiche che affliggono gli habitat urbani di Constantine sono direttamente riconducibili ai modelli prevalenti nella progettazione architettonica e urbanistica, profondamente condizionati dal paradigma razionalista occidentale, definito a partire da bisogni e forze extra-locali e sotteso a priorità dettate dall’economia di mercato capitalistica. Questo modello di sviluppo, concepito ed articolato in termini di macro-funzioni spaziali, si sta ripercuotendo in maniera fortemente negativa sul sistema territoriale e socio-economico dell’area, causando un generale degrado paesaggistico ed ambientale e l’emergenza di nuove forme di povertà fra la popolazione neo-urbana, che rappresenta la gran parte della popolazione locale. La situazione rias-sunta sopra impone a pianificatori e decisori locali di prendere in rinnovata considerazione sia la re-sponsabilità sociale implicata dalle loro pratiche professionali, sia gli effetti prodotti dalla pianificazione sugli abitanti e sul territorio nella sua globalità, rendendo dunque evidente la necessità di assumere un serio impegno verso lo sviluppo di metodologie innovative e sostenibili di analisi e pianificazione urbanistica, flessibili e sensibili al contesto, basate su un approccio interdisciplinare e partecipativo e aperte ad una costante reinterpretazione a partire dalle pratiche socio-spaziali locali.The environmental and socio-economic distortions affecting Constantine urban habitats are strictly connected to the prevailing models of architectural and urban planning, deeply influenced by the globalizing western rationalist paradigm, defined by extra-local needs and forces and driven by the priorities dictated by the capitalistic market economy. This development model, conceived and implemented in terms of universal macro-scale spatial functions, is impacting very negatively the territorial and socio-economic system of the area, generating a general environmental and landscape degradation and producing new forms of poverty within the newly urbanised groups, which represent a great portion of the local population. This situation calls planners and local decision makers to consider the social responsibility implied in their professional practices and the effects that they produce on the inhabitants and on the territory as a whole, making therefore necessary a serious commitment toward the development of an innovative and sustainable methodology of architectural and urban analysis and planning, context-sensitive and flexible, based on an interdisciplinary and participatory approach and open to a continuous re-interpretation in the light of the local social and spatial practices

The role of host PrP in Transmissible Spongiform Encephalopathies

AbstractPrP has a central role in the Transmissible Spongiform Encephalopathies (TSEs), and mutations and polymorphisms in host PrP can profoundly alter the host's susceptibility to a TSE agent. However, precisely how host PrP influences the outcome of disease has not been established. To investigate this we have produced by gene targeting a series of inbred lines of transgenic mice expressing different PrP genes. This allows us to study directly the influence of the host PrP gene in TSEs. We have examined the role of glycosylation, point mutations, polymorphisms and PrP from different species on host susceptibility and the disease process both within the murine species and across species barriers

Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties

N-Linked glycans have been shown to have an important role in the cell biology of a variety of cell surface glycoproteins, including PrP protein. It has been suggested that glycosylation of PrP can influence the susceptibility to transmissible spongiform encephalopathy and determine the characteristics of the many different strains observed in this particular type of disease. To understand the role of carbohydrates in influencing the PrP maturation, stability, and cell biology, we have produced and analyzed gene-targeted murine models expressing differentially glycosylated PrP. Transgenic mice carrying the PrP substitution threonine for asparagine 180 (G1) or threonine for asparagine 196 (G2) or both mutations combined (G3), which eliminate the first, second, and both glycosylation sites, respectively, have been generated by double replacement gene targeting. An in vivo analysis of altered PrP has been carried out in transgenic mouse brains, and our data show that the lack of glycans does not influence PrP maturation and stability. The presence of one chain of sugar is sufficient for the trafficking to the cell membrane, whereas the unglycosylated PrP localization is mainly intracellular. However, this altered cellular localization of PrP does not lead to any overt phenotype in the G3 transgenic mice. Most importantly, we found that, in vivo, unglycosylated PrP does not acquire the characteristics of the aberrant pathogenic form (PrPSc), as was previously reported using in vitro models

Defining the microglia response during the time course of chronic neurodegeneration

Inflammation has been proposed as a major component of neurodegenerative diseases, although the precise role it plays has yet to be defined. We examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a prion disease model of chronic neurodegeneration. Initially, we performed an extensive reanalysis of a large study of prion disease, where the transcriptome of mouse brains had been monitored throughout the time course of disease. Our analysis has provided a detailed classification of the disease-associated genes based on cell type of origin and gene function. This revealed that the genes upregulated during disease, regardless of the strain of mouse or prion protein, are expressed predominantly by activated microglia. In order to study the microglia contribution more specifically, we established a mouse model of prion disease in which the 79A murine prion strain was introduced by an intraperitoneal route into BALB/cJ(Fms-EGFP/−) mice, which express enhanced green fluorescent protein under the control of the c-fms operon. Samples were taken at time points during disease progression, and histological analysis of the brain and transcriptional analysis of isolated microglia was carried out. The analysis of isolated microglia revealed a disease-specific, highly proinflammatory signature in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the importance of microglia within the prion disease process and identifies the nature of the response through gene expression analysis of isolated microglia. IMPORTANCE Inflammation has been proposed as a major component of neurodegenerative diseases. We have examined the role of key contributors to this inflammatory process, microglia, the major resident immune cell population of the brain, in a murine prion disease model of chronic neurodegeneration. Our study demonstrates that genes upregulated throughout the disease process are expressed predominantly by microglia. A disease-specific, highly proinflammatory signature was observed in addition to an upregulation of genes associated with metabolism and respiratory stress. This study strongly supports the growing recognition of the important contribution of microglia to a chronic neurodegenerative disease process

The Glycosylation Status of PrPC Is a Key Factor in Determining Transmissible Spongiform Encephalopathy Transmission between Species

The risk of transmission of transmissible spongiform encephalopathies (TSE) between different species has been notoriously unpredictable because the mechanisms of transmission are not fully understood. A transmission barrier between species often prevents infection of a new host with a TSE agent. Nonetheless, some TSE agents are able to cross this barrier and infect new species, with devastating consequences. The host PrP(C) misfolds during disease pathogenesis and has a major role in controlling the transmission of agents between species, but sequence compatibility between host and agent PrP(C) does not fully explain host susceptibility. PrP(C) is posttranslationally modified by the addition of glycan moieties which have an important role in the infectious process. Here, we show in vivo that glycosylation of the host PrP(C) has a significant impact on the transmission of TSE between different host species. We infected mice carrying different glycosylated forms of PrP(C) with two human agents (sCJDMM2 and vCJD) and one hamster strain (263K). The absence of glycosylation at both or the first PrP(C) glycosylation site in the host results in almost complete resistance to disease. The absence of the second site of N-glycan has a dramatic effect on the barrier to transmission between host species, facilitating the transmission of sCJDMM2 to a host normally resistant to this agent. These results highlight glycosylation of PrP(C) as a key factor in determining the transmission efficiency of TSEs between different species. IMPORTANCE The risks of transmission of TSE between different species are difficult to predict due to a lack of knowledge over the mechanisms of disease transmission; some strains of TSE are able to cross a species barrier, while others do not. The host protein, PrP(C), plays a major role in disease transmission. PrP(C) undergoes posttranslational glycosylation, and the addition of these glycans may play a role in disease transmission. We infected mice that express different forms of glycosylated PrP(C) with three different TSE agents. We demonstrate that changing the glycosylation status of the host can have profound effects on disease transmission, changing host susceptibility and incubation times. Our results show that PrP(C) glycosylation is a key factor in determining risks of TSE transmission between species

Host PrP Glycosylation: A Major Factor Determining the Outcome of Prion Infection

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177The expression of the prion protein (PrP) is essential for transmissible spongiform encephalopathy (TSE) or prion diseases to occur, but the underlying mechanism of infection remains unresolved. To address the hypothesis that glycosylation of host PrP is a major factor influencing TSE infection, we have inoculated gene-targeted transgenic mice that have restricted N-linked glycosylation of PrP with three TSE strains. We have uniquely demonstrated that mice expressing only unglycosylated PrP can sustain a TSE infection, despite altered cellular location of the host PrP. Moreover we have shown that brain material from mice infected with TSE that have only unglycosylated PrPSc is capable of transmitting infection to wild-type mice, demonstrating that glycosylation of PrP is not essential for establishing infection within a host or for transmitting TSE infectivity to a new host. We have further dissected the requirement of each glycosylation site and have shown that different TSE strains have dramatically different requirements for each of the glycosylation sites of host PrP, and moreover, we have shown that the host PrP has a major role in determining the glycosylation state of de novo generated PrPSc.https://doi.org/10.1371/journal.pbio.00601006pubpub