Acute Administration of Non-Classical Estrogen Receptor Agonists Attenuates Ischemia-Induced Hippocampal Neuron Loss in Middle-Aged Female Rats

Pretreatment with 17beta-estradiol (E2) is profoundly neuroprotective in young animals subjected to focal and global ischemia. However, whether E2 retains its neuroprotective efficacy in aging animals, especially when administered after brain insult, is largely unknown.We examined the neuroprotective effects of E2 and two agonists that bind to non-classical estrogen receptors, G1 and STX, when administered after ischemia in middle-aged rats after prolonged ovarian hormone withdrawal. Eight weeks after ovariectomy, middle-aged female rats underwent 10 minutes of global ischemia by four vessel occlusion. Immediately after reperfusion, animals received a single infusion of either E2 (2.25 microg), G1 (50 microg) or STX (50 microg) into the lateral ventricle (ICV) or a single systemic injection of E2 (100 microg/kg). Surviving pyramidal neurons in the hippocampal CA1 were quantified 1 week later. E2 and both agonists that target non-classical estrogen receptors (G1 and STX) administered ICV at the time of reperfusion provided significant levels of neuroprotection, with 55-60% of CA1 neurons surviving vs 15% survival in controls. A single systemic injection of a pharmacological dose of E2 also rescued approximately 50% of CA1 pyramidal neurons destined to die. To determine if E2 and G1 have similar mechanisms of action in hippocampal neurons, we compared the ability of E2 and G1 to modify CA1 pyramidal neuron responses to excitatory inputs from the Schaffer collaterals recorded in hippocampal slices derived from female rats not subjected to global ischemia. E2 and G1 (10 nM) significantly potentiated pyramidal neuron responses to excitatory inputs when applied to hippocampal slices.These findings suggest (1) that middle-aged female rats retain their responsiveness to E2 even after a long period of hormone withdrawal, (2) that non-classical estrogen receptors may mediate the neuroprotective actions of E2 when given after ischemia, and (3) that the neuroprotective efficacy of estrogens may be related to their modulation of synaptic activity in hippocampal slices

"Ordinary, the same as anywhere else": notes on the management of spoiled identity in 'marginal' middle class neighbourhoods

Urban sociologists are becoming increasingly interested in neighbourhood as a source of middle-class identity. Particular emphasis is currently being given to two types of middle-class neighbourhood; gentrified urban neighbourhoods of ‘distinction’ and inconspicuous ‘suburban landscapes of privilege’. However, there has been a dearth of work on ‘marginal’ middle-class neighbourhoods that are similarly ‘inconspicuous’ rather than distinctive, but less exclusive, thus containing sources of ‘spoiled identity’. This article draws on data gathered from two ‘marginal’ middleclass neighbourhoods that contained a particular source of ‘spoiled identity’: social renters. Urban sociological analyses of neighbour responses to these situations highlight a process of dis-identification with the maligned object, which exacerbates neighbour differences. Our analysis of data from the ‘marginal’ middle-class neighbourhoods suggests something entirely different and Goffmanesque. This entailed the management of spoiled identity, which emphasized similarities rather than differences between neighbours.</p

Colour in urban places: A case study of Leicester City Football Club blue

By communicating an integrated story, the Leicester City Football Club blue inherits and persists the history and legacy of the football club, which further provides a stable and consistent meaning for the local sports culture. Colour as a medium and agency creates an intimacy and loyalty between the different ethnic and social groups across local, regional, and global contexts. The case study demonstrated that colour could give place identity through branding practice, identity mediation, and visual culture formation. The process reflected that economic and cultural force had a large impact on place‐making, and could be the decisive influence upon colour symbolism

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

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

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

Exploring attitudes to edgy urban destinations: the case of Deptford, London

The role of tourists and tourism in urban development is not fully understood. Research has focused on tourism districts within city centres, but less is known about tourism in peripheral, less affluent urban districts. These areas can appeal to visitors as edgy alternatives to mainstream destinations. This study establishes who is interested in visiting and why, and it explores the underlying rationale for negative attitudes. The aims are addressed by an in-depth analysis of Deptford in South East London. This area is a relatively deprived part of a world city, albeit one that has long been earmarked as London's next cool district. The study uses a mix of different sources to analyse the case. Responses to a New York Times article on Deptford are analysed and the attitudes of actual visitors and key stakeholders are explored. The discussion includes an examination of different interpretations and attitudes towards the notion of edginess. Edginess is deemed attractive by certain audiences; something linked to a reverence for working-class life in the arts. The study concludes that, whilst edginess is a noted characteristic, what people appreciate about Deptford is its ‘distinctive ordinariness’ – its contrast with more polished and contrived urban districts