Social movements, the European crisis, and EU political opportunities

Social movements in the wake of the financial crisis have shifted from the counter-summits and world social forums of the global justice movement to the camps of the anti-austerity mobilizations, and from a clear focus on building ‘another Europe’ to more domestically embedded issues. Among other reasons, this turn away from the EU can be linked to contracting political opportunities for social justice movements at the European level. This article addresses the closure of opportunities at the EU level for the work of social movement groups campaigning on specific EU policies. We reflect on the complexity of the EU’s political opportunity structure prior to the financial crisis, before examining changes to the EU’s architecture effected through responses to the crises and outlining arguments on how EU level opportunities around socio-economic issues in particular have shrunk as a result. We then show how the perception of other political opportunities at the EU level is affected by the austerity response by drawing on campaigns that sought to exploit new opportunities included in the Lisbon Treaty and designed to increase citizens’ input. Opportunities introduced by changes made in the Lisbon Treaty are perceived through the prism of contracted opportunities flowing from power shifts caused by the response to the financial crisis

The STAFF-DWP wave instrument on the DSP equatorial spacecraft: description and first results

The STAFF-DWP wave instrument on board the equatorial spacecraft (TC1) of the Double Star Project consists of a combination of 2 instruments which are a heritage of the Cluster mission: the Spatio-Temporal Analysis of Field Fluctuations (STAFF) experiment and the Digital Wave-Processing experiment (DWP). On DSP-TC1 STAFF consists of a three-axis search coil magnetometer, used to measure magnetic fluctuations at frequencies up to 4 kHz and a waveform unit, up to 10 Hz, plus snapshots up to 180 Hz. DWP provides several onboard analysis tools: a complex FFT to fully characterise electromagnetic waves in the frequency range 10 Hz-4 kHz, a particle correlator linked to the PEACE electron experiment, and compression of the STAFF waveform data. The complementary Cluster and TC1 orbits, together with the similarity of the instruments, permits new multi-point studies. The first results show the capabilities of the experiment, with examples in the different regions of the magnetosphere-solar wind system that have been encountered by DSP-TC1 at the beginning of its operational phase. An overview of the different kinds of electromagnetic waves observed on the dayside from perigee to apogee is given, including the different whistler mode waves (hiss, chorus, lion roars) and broad-band ULF emissions. The polarisation and propagation characteristics of intense waves in the vicinity of a bow shock crossing are analysed using the dedicated PRASSADCO tool, giving results compatible with previous studies: the broad-band ULF waves consist of a superimposition of different wave modes, whereas the magnetosheath lion roars are right-handed and propagate close to the magnetic field. An example of a combined Cluster DSP-TC1 magnetopause crossing is given. This first case study shows that the ULF wave power intensity is higher at low latitude (DSP) than at high latitude (Cluster). On the nightside in the tail, a first wave event comparison - in a rather quiet time interval - is shown. It opens the doors to future studies, such as event timing during substorms, to possibly determine their onset location

“A few sparks of inspiration”?: Analysing the outcomes of European Union cultural policy coordination

This article examines the outcomes of cultural policy coordination in the European Union using a case study of one policy priority in the 2011–2014 Work Plan for Culture. The Open Method of Coordination brings Member States together to exchange and cooperate on key policy priorities. Drawing on interviews with key actors as well as participant observation material, the article demonstrates the limited influence of the culture OMC on domestic policy, showing that domestic usage tends to be on the scale of individuals and organisations rather than Member State-wide. The article finishes by contextualising the outcomes, highlighting the constraints and challenges of intergovernmental coordination in fields where the EU holds a supporting competence

Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets.

OBJECTIVE: Triomune Baby and Junior have been developed in response to the urgent need for appropriate paediatric fixed-dose combination antiretroviral tablets, with higher nevirapine to stavudine and lamivudine ratios than adult tablets, in accordance with paediatric recommendations. We determined whether this ratio results in optimal exposure in the target population. METHODS: Seventy-one Zambian children were treated with Triomune Baby or Junior dosed according to weight bands. After 4 weeks or more, a 12-h pharmacokinetic curve was recorded. Antiretroviral plasma concentrations were assayed by high-performance liquid chromatography. RESULTS: Six children were excluded because of poor adherence. Of the remaining 65, 24 (37%) were female, 24 (37%) weighed less than 15 kg and most were malnourished. Mean (range) nevirapine C12h, Cmax and AUC12h of 6.0 (1.4, 16.9) mg/l, 10.0 (3.8, 22.5) mg/l and 94.4 (32.1, 232) mg/l per hour were higher than those reported in adults. Nevirapine C12h was subtherapeutic (< 3.0 mg/l) in four children (6%). Mean stavudine and lamivudine C12h, Cmax, AUC12h (< 0.015 mg/l, 0.45 mg/l, 1.05 mg/l per hour and 0.09 mg/l, 1.33 mg/l, 5.42 mg/l per hour) were comparable to adults. There was no evidence of a difference in nevirapine AUC12h across weight bands (P = 0.2), whereas the difference in stavudine (P = 0.0003) and lamivudine AUC12h (P = 0.01) was driven by the single weight band with unequal dosing. CONCLUSION: Nevirapine concentrations were higher but more variable than in adults; the pharmacokinetic parameters of stavudine and lamivudine were comparable to adults. As nevirapine underdosing is of greater concern than overdosing, the Triomune Baby and Junior ratio appears to be appropriate for children weighing 6 kg and over. Further research is required for children under 6 kg

Transplantation of Quail Collagen-tailed Acetylcholinesterase Molecules Onto the Frog Neuromuscular Synapse

The highly organized pattern of acetylcholinesterase (AChE) molecules attached to the basal lamina of the neuromuscular junction (NMJ) suggests the existence of specific binding sites for their precise localization. To test this hypothesis we immunoaffinity purified quail globular and collagen-tailed AChE forms and determined their ability to attach to frog NMJs which had been pretreated with high-salt detergent buffers. The NMJs were visualized by labeling acetylcholine receptors (AChRs) with TRITC-α-bungarotoxin and AChE by indirect immunofluorescence; there was excellent correspondence (>97%) between the distribution of frog AChRs and AChE. Binding of the exogenous quail AChE was determined using a speciesspecific monoclonal antibody. When frog neuromuscular junctions were incubated with the globular G4/G2 quail AChE forms, there was no detectable binding above background levels, whereas when similar preparations were incubated with the collagen-tailed A12 AChE form >80% of the frog synaptic sites were also immunolabeled for quail AChE attached. Binding of the A12 quail AChE was blocked by heparin, yet could not be removed with high salt buffer containing detergent once attached. Similar results were obtained using empty myofiber basal lamina sheaths produced by mechanical or freeze-thaw damage. These experiments show that specific binding sites exist for collagen-tailed AChE molecules on the synaptic basal lamina of the vertebrate NMJ and suggest that these binding sites comprise a “molecular parking lot” in which the AChE molecules can be released, retained, and turned over

Pharmacological screening using an FXN-EGFP cellular genomic reporter assay for the therapy of Friedreich ataxia

Copyright @ 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. There is a correlation between expansion length, the amount of residual frataxin and the severity of disease. As the coding sequence is unaltered, pharmacological up-regulation of FXN expression may restore frataxin to therapeutic levels. To facilitate screening of compounds that modulate FXN expression in a physiologically relevant manner, we established a cellular genomic reporter assay consisting of a stable human cell line containing an FXN-EGFP fusion construct, in which the EGFP gene is fused in-frame with the entire normal human FXN gene present on a BAC clone. The cell line was used to establish a fluorometric cellular assay for use in high throughput screening (HTS) procedures. A small chemical library containing FDA-approved compounds and natural extracts was screened and analyzed. Compound hits identified by HTS were further evaluated by flow cytometry in the cellular genomic reporter assay. The effects on FXN mRNA and frataxin protein levels were measured in lymphoblast and fibroblast cell lines derived from individuals with FRDA and in a humanized GAA repeat expansion mouse model of FRDA. Compounds that were established to increase FXN gene expression and frataxin levels included several anti-cancer agents, the iron-chelator deferiprone and the phytoalexin resveratrol.Muscular Dystrophy Association (USA), the National Health and Medical Research Council (Australia), the Friedreich’s Ataxia Research Alliance (USA), the Brockhoff Foundation (Australia), the Friedreich Ataxia Research Association (Australasia), Seek A Miracle (USA) and the Victorian Government’s Operational Infrastructure Support Program

Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult mdx Mice

Duchenne muscular dystrophy (DMD) is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myogflox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myogflox/flox mice (mdx), Myogflox/flox mice (wild-type), and mdx:MyogfloxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted). mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function