There is a huge disparity between what the Scottish pro-independence camp demands from the EU and what it offers

SAMSUNG CSCA newly independent Scotland will have to work out many issues, not least its relationship with the EU. Unhelpfully, writes Sasha Vereker, the Yes camp has staked out a harsh negotiating stance with on the EU. It wants to retain all the advantages it currently enjoys as a member of the UK, such as the budget rebate, while renegotiating other aspects, such as the Common Fishing Policy

After Baines

By researching the life and work of Thomas Baines (1820 - 1875) in relation to a broader discourse of painting and the lived experience of being a 'white' male in a post-apartheid South Africa, I explore the ways in which this figure from the past has provoked the three series of artworks I have produced for my Master of Fine Art exhibition. This study has been divided into two parts, represented by the two chapters contained herein. Chapter One includes a critical retelling of Baines' biography and a discussion of the primary ways in which I have engaged with both the life and the working practice of this artist. I also address my own personal complicity in the constructions of 'the figure of Baines' as I have framed him both visually and textually during my work for this degree. Chapter Two describes some of the practicalities of my working process as a visual artist, including how I understand the theoretical and conceptual concerns which I raise in Chapter One to be visually manifest in my work. In this chapter, I also discuss my work in relation to the work of the contemporary South African artists William Kentridge and Johannes Phokela. The artistic practice of one artist imitating another artist's work is also explored as a central conceptual thread which could be seen to weave my verbal and visual production together

A pivotal role for interleuking-4 in Atorvastatin-associated neuroprotection in rat brain.

noInflammatory changes, characterized by an increase in pro-inflammatory cytokine production and up-regulation of the corresponding signaling pathways, have been described in the brains of aged rats and rats treated with the potent immune modulatory molecule lipopolysaccharide (LPS). These changes have been coupled with a deficit in long-term potentiation (LTP) in hippocampus. The evidence suggests that anti-inflammatory agents, which attenuate the LPS-induced and age-associated increase in hippocampal interleukin-1ß (IL-1ß) concentration, lead to restoration of LTP. Here we report that atorvastatin, a member of the family of agents that act as inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, exerts powerful anti-inflammatory effects in brain and that these effects are mediated by IL-4 and independent of its cholesterol-lowering actions. Treatment of rats with atorvastatin increased IL-4 concentration in hippocampal tissue prepared from LPS-treated and aged rats and abrogated the age-related and LPS-induced increases in pro-inflammatory cytokines, interferon-¿ (IFN¿) and IL-1ß, and the accompanying deficit in LTP. The effect of atorvastatin on the LPS-induced increases in IFN¿ and IL-1ß was absent in tissue prepared from IL-4¿/¿ mice. The increase in IL-1ß in LPS-treated and aged rats is associated with increased microglial activation, assessed by analysis of major histocompatibility complex II expression, and the evidence suggests that IFN¿ may trigger this activation. We propose that the primary effect of atorvastatin is to increase IL-4, which antagonizes the effects of IFN¿, the associated increase in microglial activation, and the subsequent cascade of events

The Neuronal EGF-Related Gene Nell2 Interacts with Macf1 and Supports Survival of Retinal Ganglion Cells after Optic Nerve Injury

Nell2 is a neuron-specific protein containing six epidermal growth factor-like domains. We have identified Nell2 as a retinal ganglion cell (RGC)-expressed gene by comparing mRNA profiles of control and RGC-deficient rat retinas. The aim of this study was to analyze Nell2 expression in wild-type and optic nerve axotomized retinas and evaluate its potential role in RGCs. Nell2-positive in situ and immunohistochemical signals were localized to irregularly shaped cells in the ganglion cell layer (GCL) and colocalized with retrogradely-labeled RGCs. No Nell2-positive cells were detected in 2 weeks optic nerve transected (ONT) retinas characterized with approximately 90% RGC loss. RT-PCR analysis showed a dramatic decrease in the Nell2 mRNA level after ONT compared to the controls. Immunoblot analysis of the Nell2 expression in the retina revealed the presence of two proteins with approximate MW of 140 and 90 kDa representing glycosylated and non-glycosylated Nell2, respectively. Both products were almost undetectable in retinal protein extracts two weeks after ONT. Proteome analysis of Nell2-interacting proteins carried out with MALDI-TOF MS (MS) identified microtubule-actin crosslinking factor 1 (Macf1), known to be critical in CNS development. Strong Macf1 expression was observed in the inner plexiform layer and GCL where it was colocalizied with Thy-1 staining. Since Nell2 has been reported to increase neuronal survival of the hippocampus and cerebral cortex, we evaluated the effect of Nell2 overexpression on RGC survival. RGCs in the nasal retina were consistently more efficiently transfected than in other areas (49% vs. 13%; n = 5, p<0.05). In non-transfected or pEGFP-transfected ONT retinas, the loss of RGCs was approximately 90% compared to the untreated control. In the nasal region, Nell2 transfection led to the preservation of approximately 58% more cells damaged by axotomy compared to non-transfected (n = 5, p<0.01) or pEGFP-transfected controls (n = 5, p<0.01)

Systemic TNF-α produces acute cognitive dysfunction and exaggerated sickness behavior when superimposed upon progressive neurodegeneration

AbstractInflammation influences chronic neurodegeneration but its precise roles are not yet clear. Systemic inflammation caused by infection, trauma or co-morbidity can alter the brain’s inflammatory status, produce acute cognitive impairments, such as delirium, and drive new pathology and accelerated decline. Consistent with this, elevated systemic TNF-α is associated with more rapid cognitive decline over 6months in Alzheimer’s disease patients. In the current study we challenged normal animals and those with existing progressive neurodegeneration (ME7 prion disease) with TNF-α (i.p.) to test the hypothesis that this cytokine has differential effects on cognitive function, sickness behavior and features of underlying pathology contingent on the animals’ baseline condition. TNF-α (50μg/kg) had no impact on performance of normal animals (normal brain homogenate; NBH) on working memory (T-maze) but produced acute impairments in ME7 animals similarly challenged. Plasma TNF-α and CCL2 levels were equivalent in NBH and ME7 TNF-challenged animals but hippocampal and hypothalamic transcription of IL-1β, TNF-α and CCL2 and translation of IL-1β were higher in ME7+TNF-α than NBH+TNF-α animals. TNF-α produced an exaggerated sickness behavior response (hypothermia, weight loss, inactivity) in ME7 animals compared to that in NBH animals. However a single challenge with this dose was not sufficient to produce de novo neuronal death, synaptic loss or tau hyperphosphorylation that was distinguishable from that arising from ME7 alone. The data indicate that acutely elevated TNF-α has robust acute effects on brain function, selectively in the degenerating brain, but more sustained levels may be required to significantly impact on underlying neurodegeneration

A role for interleukin-1? in synaptic function

THESIS 6174The proinflammatory cytokine, interleukin-1? (IL -1? ). one of the most extensively studied cytokines to date, is known to play a pivotal role in neurodegenerative, inflammatory and infectious diseases. Moreover, IL-1? has been implicated in the impairment of long-term potentiation (LTP), a model for learning and memory, and at least one biochemical correlate associated with LTP, i.e., glutamate release. The mechanisms underlying the impairment of LTP in deleterious circumstances, such as in ageing, remains to be fully elucidated. The focus of this study involved investigating the possibility that the stress-activated protein kinases, JNK and p38, underlie this impairment and that activation is initiated by an increase in IL -1? concentration and reactive oxygen species (ROS) formation