A novel mutation in the N-terminal acting-binding domain of Filamin C protein causing a distal myofibrillar myopathy

Variants in Filamin C (FLNC) gene may cause either cardiomyopathies or different myopathies. We describe a family affected by a distal myopathy with autosomal dominant inheritance. The onset of the disease was in the third decade with gait impairment due to distal leg weakness. Subsequently, the disease progressed with an involvement of proximal lower limbs and hand muscles. Muscle biopsy, performed in one subject,identified relevant myofibrillar abnormalities. We performed a target gene panel testing for myofibrillar myopathies by NGS approach which identified a novel mutation in exon 3 of FLNC gene (c.A664G:p.M222V), within the N-terminal actin-binding (ABD) domain. This variant has been identified in all affected members of the family, thus supporting its pathogenic role. Differently from previously identified variants, our family showed a predominant leg involvement and myofibrillar aggregates, thus further expanding the spectrum of Filamin C related myopathies

The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment

Aims SPTLC1-related disorder is a late onset sensory-autonomic neuropathy associated with perturbed sphingolipid homeostasis which can be improved by supplementation with the serine palmitoyl-CoA transferase (SPT) substrate, l-serine. Recently, a juvenile form of motor neuron disease has been linked to SPTLC1 variants. Variants affecting the p.S331 residue of SPTLC1 cause a distinct phenotype, whose pathogenic basis has not been established. This study aims to define the neuropathological and biochemical consequences of the SPTLC1 p.S331 variant, and test response to l-serine in this specific genotype. Methods We report clinical and neurophysiological characterisation of two unrelated children carrying distinct p.S331 SPTLC1 variants. The neuropathology was investigated by analysis of sural nerve and skin innervation. To clarify the biochemical consequences of the p.S331 variant, we performed sphingolipidomic profiling of serum and skin fibroblasts. We also tested the effect of l-serine supplementation in skin fibroblasts of patients with p.S331 mutations. Results In both patients, we recognised an early onset phenotype with prevalent progressive motor neuron disease. Neuropathology showed severe damage to the sensory and autonomic systems. Sphingolipidomic analysis showed the coexistence of neurotoxic deoxy-sphingolipids with an excess of canonical products of the SPT enzyme. l-serine supplementation in patient fibroblasts reduced production of toxic 1-deoxysphingolipids but further increased the overproduction of sphingolipids. Conclusions Our findings suggest that p.S331 SPTLC1 variants lead to an overlap phenotype combining features of sensory and motor neuropathies, thus proposing a continuum in the spectrum of SPTLC1-related disorders. l-serine supplementation in these patients may be detrimental

Power Stations and Petroleum Heritage in Italy. The case of Porto Tolle

Combining various streams of literature on marginal territories and “operational landscapes,” this chapter considers a particular type of petroleumscape, one in which oil is transformed into electricity. In the context of the current energy transition, oil-fueled power plants become outdated, while their physical structures may remain. They can be interpreted as the heritage of the future. Entering an area given little attention in urban, landscape, and architecture scholarship, Chiara Geroldi and Gloria Pessina investigate unused and underused oil-fueled thermoelectric power stations in Italy, highlighting architectural elements, flows of oil, infrastructure, and social conflict. The station this chapter discusses in the most detail, Porto Tolle, is located in the fragile portion of the Po River delta known as Polesine, which has been marked by contentious processes of development and heritagization for several decades. By recognizing the role Porto Tolle has played in the global petroleumscape and highlighting its specific historical, geographical, environmental, and sociopolitical features, the authors imagine a post-oil future for Polesine, aimed at reconciling the broken equilibrium between land, water, and oil and at overcoming harmful economic development models

Spectacle Island: From discarded fill to designed landscape, a ‘natural’-looking park

Spectacle Island used to host disagreeable activities, including a dump site for the city of Boston. In the 1990s, the island received a significant amount of the Central Artery/Tunnel Project (CA/T) excavated materials. As part of the CA/T Project, also known as the ‘Big Dig’, Spectacle Island was reclaimed and made into a public park. By analyzing Spectacle Island and the process of its construction, this article aims to show that ‘discarded fill’ can be successfully addressed by the design disciplines within a collaborative environment, rather than by technical experts only, as usually happens. Moreover, given the scarcity of literature on the topic, this article aims to contribute to the field by identifying several considerations useful to addressing discarded fill from a design perspective: the complexity of discarded materials management, the possible value of placing discarded materials on visible sites, the different ways in which it is possible to convey the identity of the landscapes constructed with discarded fill, and, finally, the possible role of designers. © 2018; Routledge. All Rights Reserved

Reading the territory through maps, timelines, sections, and flow representations

Maps are developed first to know, then to act, as André Corboz notes in his influential text on the territory as a palimpsest written in 1983. Maps can provide new knowledge and a new understanding of a territory, and they permit one to make a step toward the design project. Maps can be profitably developed by selecting layers to be represented, pursuant to the method developed by Ian McHarg, considered an antecedent to GIS, which was subsequently adopted and reinterpreted by many. By critically selecting and overlapping layers, representing both material and immaterial conditions, one can reveal existing relationships in a given territory. Timelines represent another meaningful tool for depicting transformations: the sequences of events affecting a territory and their relationships with global events and/or policies can reveal ongoing trajectories of development. Sections have a tradition in the planning and landscape architecture fields - from those elaborated by Alexander von Humboldt showing the relationship between altitudes and species, to the Patrick Geddes’ valley section, to the contemporary examples of Bernardo Secchi and Paola Viganò. They are a useful tool for addressing the ground and its thickness. Representing the flows of materials by means of maps or sections, as often done by Pierre Bélanger, can offer important insights for landscape projects, highlighting opportunities for intervention. Conveying this type of metabolic perspective to students is highly important today, to stimulate their awareness of the flows of materials and waste generation. This contribution will gather examples - maps, timelines, sections, and flow representations – including student work developed in landscape architecture modules at Politecnico di Milano, to show possible ways to read the territory for future landscape architects

Social inequalities and their spatial expression in the city of Shenzhen

This paper has analysed the inequalities that can be observed in the city of Shenzhen, and illustrated their relationship with the hukou system. Furthermore, the paper has explained the correlation between the growth of inequalities and the competiveness of the city. Chinese migrants do not possess the urban hukou of the city they arrive in, and, therefore, they are excluded from 'the right to the city'. Moreover, they are usually paid lower wages than urban residents. The paper has shown that the floaters in Shenzhen have limited access to highly paid jobs, for instance in State Owned Enterprises, in comparison to urban residents. Consequently, they have low access to the standard housing market: most of them, in fact, live in urban villages, especially in Non-Sez districts. In order to analyse the relationship between the growth of the city and the growth of inequalities, the labour trends from 1979 to 2009 have been taken into consideration. These show that the increase of Shenzhen Gdp and the presence of foreign investments are linked to the growth of the so called Non-Zhigong labour, which is characterized by low income positions, mostly involving migrants. The paper has also shown that there is an increasing polarization in absolute terms (increasing number of migrants) and a decreasing one in relative terms (decreasing proportion of migrants respect to the total of the population). The narrowing of the gap in relative terms could be explained by thinking about the economic shift of the city, especially in connection to the return of Honk Kong to China as a Sar, and its partial deindustrialization. The growth of the city has been accompanied by an increasing densification of the urban villages. The urban villages represent a spatial manifestation of social inequalities: the low cost of living in these areas makes it possible to keep low wages in the industrial and service sectors that, in turn, encourage the competiveness of Shenzhen. The role played by policies has proved fundamental in enhancing both the growth of the city and the presence of disparities. The most important involves the hukou system and the regional development policies (such as the setting of the Special Economic Zones). Moreover, the land market reforms and the strategy in respect of the urban villages have also contributed to the spatial expansion of the city and to the growth of inequalities. Further possible analysis may concern the relationship between the changes in the housing market after the reform of 1988 and their impact on the redevelopment of urban villages, which are now attracting speculative interests. Moreover, an interesting issue emerged which could deserve future investigations: the relationship between the changing proportion and numbers of migrants and resident population in relation to polarization, professionalization and the chances for the development of a middle class. Copyright © Franco Angeli

Energia: l'impresa dei flussi | Energy: the flow firm

Il contributo definisce L’Impresa dei Flussi di Energia, ovvero un tipo di impresa che si occupa di quella merce non facilmente stoccabile che è l’energia elettrica. In particolare guarda alla principale azienda dell’elettricità italiana, Enel, osservandone la sua modificazione, dalla nascita come impresa di Stato alla sua attuale configurazione come multinazionale e società per azioni, e ai suoi passi più recenti nel contesto della transizione energetica. Il contributo si concentra in particolare sul progetto “Futur-e”, promosso da Enel al fine di chiudere e accompagnare la riconversione di 23 centrali termoelettriche in Italia. Viene avanzata una prima riflessione sui rapporti tra Enel e alcuni territori delle centrali interessate dal progetto Futur-e, mostrando la relazione che esisteva in passato, le modalità di accompagnamento della chiusura degli impianti e le reazioni delle comunità e delle istituzioni locali. In conclusione viene proposta una riflessione sui rapporti tra scala globale e locale, in particolare sui processi di territorializzazione/deterritorializzazione che sembrano interessare l’azienda.The chapter defines The Energy Flows’ Firm, i.e. a typology of firm which deals with a not easily storable and constantly on the move good as electricity. In particular, we analyse the main Italian enterprise active in the field of electricity, Enel, by observing its evolution, from the start as a state firm to the current organisation as a multinational in the context of energy transition. The chapter focuses in particular on the “Futur-e” project, promoted by Enel with the aim to accompany the regeneration of 23 thermoelectric power stations in Italy. The paper proposes a first reflection on the relation between Enel and some of the territories of the Futur-e power stations, showing the previous connections, the forms of accompaniment to the closure of the plants and the reactions by the local communities and institutions. In conclusion, the chapter reflects on the relation between global and local scale, and in particular on the processes of territorialisation and deterritorialisation in which the firm is involved