A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders.

Altered synaptic structure and function is a major hallmark of fragile X syndrome (FXS), autism spectrum disorders (ASDs), and other intellectual disabilities (IDs), which are therefore classified as synaptopathies. FXS and ASDs, while clinically and genetically distinct, share significant comorbidity, suggesting that there may be a common molecular and/or cellular basis, presumably at the synapse. In this article, we review brain architecture and synaptic pathways that are dysregulated in FXS and ASDs, including spine architecture, signaling in synaptic plasticity, local protein synthesis, (m)RNA modifications, and degradation. mRNA repression is a powerful mechanism for the regulation of synaptic structure and efficacy. We infer that there is no single pathway that explains most of the etiology and discuss new findings and the implications for future work directed at improving our understanding of the pathogenesis of FXS and related ASDs and the design of therapeutic strategies to ameliorate these disorders

Dark matter halo's and self similarity

This papers explores the self similar solutions of the Vlasov-Poisson system and their relation to the gravitational collapse of dynamically cold systems. Analytic solutions are derived for power law potential in one dimension, and extensions of these solutions in three dimensions are proposed. Next the self similarity of the collapse of cold dynamical systems is investigated numerically. The fold system in phase space is consistent with analytic self similar solutions, the solutions present all the proper self-similar scalings. An additional point is the appearance of an $x^{-(1/2)}$ law at the center of the system for initial conditions with power law index larger than $-(1/2)$. It is found that the first appearance of the $x^{-(1/2)}$ law corresponds to the formation of a singularity very close to the center. Finally the general properties of self similar multi dimensional solutions near equilibrium are investigated. Smooth and continuous self similar solutions have power law behavior at equilibrium. However cold initial conditions result in discontinuous phase space solutions, and the smoothed phase space density looses its auto similar properties. This problem is easily solved by observing that the probability distribution of the phase space density $P$ is identical except for scaling parameters to the probability distribution of the smoothed phase space density $P_S$. As a consequence $P_S$ inherit the self similar properties of $P$. This particular property is at the origin of the universal power law observed in numerical simulation for ${\rho}/{\sigma^3}$. The self similar properties of $P_S$ implies that other quantities should have also an universal power law behavior with predictable exponents. This hypothesis is tested using a numerical model of the phase space density of cold dark matter halo's, an excellent agreement is obtained.Comment: Final versio

Hobson’s choice? Constraints on accessing spaces of creative production

Successful creative production is often documented to occur in urban areas that are more likely to be diverse, a source of human capital and the site of dense interactions. These accounts chart how, historically, creative industries have clustered in areas where space was once cheap in the city centre fringe and inner city areas, often leading to the development of a creative milieu, and thereby stimulating further creative production. Historical accounts of the development of creative areas demonstrate the crucial role of accessible low-cost business premises. This article reports on the findings of a case study that investigated the location decisions of firms in selected creative industry sectors in Greater Manchester. The study found that, while creative activity remains highly concentrated in the city centre, creative space there is being squeezed and some creative production is decentralizing in order to access cheaper premises. The article argues that the location choices of creative industry firms are being constrained by the extensive city centre regeneration, with the most vulnerable firms, notably the smallest and youngest, facing a Hobson’s choice of being able to access low-cost premises only in the periphery. This disrupts the delicate balance needed to sustain production and begs the broader question as to how the creative economy fits into the existing urban fabric, alongside the competing demands placed on space within a transforming industrial conurbation

Grassroots Creative Hubs: Urban Regeneration, Recovered Industrial Factories and Cultural Production in Buenos Aires and Rio de Janeiro

This chapter examines the nature, functioning and politics of grassroots creative hubs as contained in refurbished industrial factories. The renewal and transformation of factories into arts and cultural venues has been a key feature of post-industrial urbanism in the last three decades. Examples abound across the world, from railway and power stations to post office buildings and chocolate factories, these recovered infrastructures have been re-signified as cultural facilities – performing or multi-arts centres, galleries, cultural centres, creative economy laboratories, incubators and museums. These initiatives, be that they are led by local governments or community groups, are part of broader urban strategies for revitalising historical centres, revalorising cultural heritage and creating work opportunities as well as resources for tourism and business investment. But can a factory building be considered a creative hub? Does the materiality of these urban artefacts provide a solution to the oftentransient nature of ephemeral cultural urbanism? Refurbishing old industrial factories and warehouses for cultural use and creative production has been the subject of much investigation since the 1980s-1990s, mainly through the study of culture-led urban regeneration and gentrification (Zukin, 1989; Montgomery, 1995; Evans and Shaw, 2004; Mommaas, 2004; Pratt, 2009), and more recently, creative industry clusters and districts (Evans, 2009; Zukin and Braslow, 2011; O’Connor and Gu, 2012). These studies have pointed out the problems that arise from the organisation, management and long-term sustainability of converted industrial sites, as well as from the policy uses and abuses that often pave the way to real-estate development and social displacement. Drawing on insights from urban sociology and critical geography, the chapter conducts a case-study analysis of two cultural and creative economy factories in Latin America: Fábrica Bhering in Rio de Janeiro, Brazil, and IMPA, la Fábrica Cultural in Buenos Aires, Argentina. The chapter is comprised of three sections: the first discusses whether recovered industrial factories can be thought of as creative hubs in relation to ephemeral cultural urbanism; the second examines the two case-studies in the context of Brazil and Argentina; and the third offers concluding remarks. Overall the chapter contributes a Latin American perspective on culture-led urban regeneration to the study of creative hubs. Particularly, grassroots creative initiatives of urban renewal are presented as an alternative to the exclusionary gentrification processes to which creative hubs and other territorial forms of creativity are often related to, in times largely shaped by neoliberal operations driven by real-estate interests and alliances between political and economic urban elites

Manageable creativity

This article notes a perception in mainstream management theory and practice that creativity has shifted from being disruptive or destructive to 'manageable'. This concept of manageable creativity in business is reflected in a similar rhetoric in cultural policy, especially towards the creative industries. The article argues that the idea of 'manageable creativity' can be traced back to a 'heroic' and a 'structural' model of creativity. It is argued that the 'heroic' model of creativity is being subsumed within a 'structural' model which emphasises the systems and infrastructure around individual creativity rather than focusing on raw talent and pure content. Yet this structured approach carries problems of its own, in particular a tendency to overlook the unpredictability of creative processes, people and products. Ironically, it may be that some confusion in our policies towards creativity is inevitable, reflecting the paradoxes and transitions which characterise the creative process

Rudolf Otto’s ‘The Absolute Other’ and a radical postsecular urban contextualization

This article proposes an idea of radical urban contextualisation that follows Rudolf Otto’s discussion on an encounter with the Absolute Other. The article critically reviews current applications of postsecularism to urban theory formulated in a general framework of Jurgen Habermas’ intervention in the early 21st century. The article argues that contemporary postsecular urban theory cannot fully answer fundamental challenges that contemporary cities are facing – both political and environmental – mostly because it focuses on linguistic and cultural aspects of a city. The article proposes the ‘radicalization’ of postsecularism, engaging directly with the ‘religious experience’ defined by Rudolf Otto as an encounter with The Absolute Other – the unknown and unpredictable. The Absolute Other notion allows to ultimately contextualize every urban situation in order to formulate conditions for future-oriented (post-capitalist) urbanism

Early uneven ear input induces long-lasting differences in left-right motor function

How asymmetries in motor behavior become established normally or atypically in mammals remains unclear. An established model for motor asymmetry that is conserved across mammals can be obtained by experimentally inducing asymmetric striatal dopamine activity. However, the factors that can cause motor asymmetries in the absence of experimental manipulations to the brain remain unknown. Here, we show that mice with inner ear dysfunction display a robust left or right rotational preference, and this motor preference reflects an atypical asymmetry in cortico-striatal neurotransmission. By unilaterally targeting striatal activity with an antagonist of extracellular signal-regulated kinase (ERK), a downstream integrator of striatal neurotransmitter signaling, we can reverse or exaggerate rotational preference in these mice. By surgically biasing vestibular failure to one ear, we can dictate the direction of motor preference, illustrating the influence of uneven vestibular failure in establishing the outward asymmetries in motor preference. The inner ear±induced striatal asymmetries identified here intersect with non±ear-induced asymmetries previously linked to lateralized motor behavior across species and suggest that aspects of left±right brain function in mammals can be ontogenetically influenced by inner ear input. Consistent with inner ear input contributing to motor asymmetry, we also show that, in humans with normal ear function, the motor-dominant hemisphere, measured as handedness, is ipsilateral to the ear with weaker vestibular input. Despite a long-standing fascination with asymmetries in left±right brain function, very little is known about the causes of functional brain asymmetry in mammals, which appear independent of the mechanisms that create anatomical asymmetries during development. Asymmetries in motor function are a common example and include preferred turning direction, handedness, and footedness. In this study, using mouse models, we establish a causal link between transient imbalances in degenerating inner ear function and the establishment of stable asymmetries in neural pathways that regulate motor activity and in motor behavior. Our study also suggests that shared mechanisms may underlie lateralized motor behaviors across mammalian species. For example, we show that in humans with normal ear function, the strength of the vestibular response from each ear in the forebrain correlates with asymmetric motor behavior, measured as handedness. In a broader sense, our study reveals a conceptually novel role for sensory input in shaping the asymmetric distribution of brain function, a process for which there is otherwise no clear mechanism

Entrepreneurial orientation of traditional and modern cultural organisations: cases in George Town UNESCO World Heritage Site

George Town World Heritage Site in Penang, Malaysia is well-endowed with creative and cultural resources, and has recently witnessed a rise in relevant rise in creative and cultural activities. This study examines how 'innovation culture' is inculcated and embedded within two local organisations with distinct approaches to innovation. This examination adopts and adapts the concept of Entrepreneurial Orientation, using three constructs: i) innovativeness, ii) risk-taking and iii) pro-activeness. This study administered a purely qualitative research approach by conducting in-depth semi-structured interviews and archival study of the chosen case organisations and their networks. The novelty of this research resides in the choice of case study organisations chosen (i.e. traditional versus modern) where a comparative approach was used to compare and contrast innovation culture and gauge the extent upon which entrepreneurship orientation constructs are prevalent and thriving in these organisations. By documenting the linkages in their value chains, this study managed to understand their resulting social networks and whether such network fosters the incubation of an innovation cluster for the local creative and cultural sectors. This study concluded that traditional cultural organisations tend to be more cautious and even passive in their business approach and decision-making processes, while modern and newer cultural and creative organisations lean towards a more active and dynamic outlook, albeit sometimes constrained by lack of resources, i.e. funding and facilities, as well as impeded by the nature of their informality. These findings can contribute towards shaping pragmatic human resource and creative industry policies for city planners and policy makers, particularly in the George Town World Heritage Site, as well as serving as point of reference for other world heritage sites in the world

Making sense of urban food festivals: cultural regeneration, disorder and hospitable cities

This article examines urban food festivals, and in doing so it carries out a case study of Nottingham’s Food and Drink Festival (NFDF). It contends that such festivals need to be understood in relation to local contexts, such as the reputation for alcohol-related disorder associated with Nottingham’s night-time economy. Rather than being used to attract tourism, NFDF was primarily directed at existing residents of Nottingham, where it sought to produce particular kinds of guests who would be able to invest in the city’s wider regeneration. Here, the article draws on recent academic work on hospitality in demonstrating how NFDF attempted to rebrand the city centre as a more hospitable place. It concludes by showing how visitors to NFDF exhibited a sense of generosity and pride, and argues that the meaning of urban food festivals cannot therefore simply be reduced to the logic of neoliberal governance

The promise of the affordable artist's studio: Governing creative spaces in London

The role of artists' organisations in populating and popularising postindustrial urban areas is well documented. However, what are less apparent are analyses of how spaces of artistic production are organised and governed in these areas. This paper explores, via an analysis of organisational documents and practices, the techniques used by London-based affordable studio providers to imagine, calculate, and make material low-cost workspace for artists. The argument made is that the negotiation of competing agendas around the production of cultural, economic, and social benefit by affordable studio providers has led to the emergence of a specific form of affordable studio. This analysis will thus show how configurations of creative space emerge from mundane techniques of measurement and governance. © 2013 Pion and its Licensors