Upploppet som det absoluta konstverket

In this article, we suggest that the notion of “aesthetic cultures of protest” can be understood as designating two broad tendencies in the contemporary field of art and politics: on the one hand, the incorporation of the protest by the art world and, on the other hand, the appropriation of aesthetic traits by social protests. To counteract the ethical immediacy of both, we turn to Theodor W. Adorno’s more dialectical understanding of the relationship between protests and the aesthetic. After being marshalled against art’s internalisation of protest, and the protests’ appropriation of the aesthetic, we assess Adorno’s notion of form and autonomy through an immanent critique that is both conceptual and historical. We argue that Adorno’s aesthetics lacks an understanding of social labour, to which it itself ascribes great conceptual significance, and that recent changes in the global composition of capital and labour has affected the role of social labour in such a way that Adorno’s tendency to identify art’s autonomy with its negativity can no longer be upheld. Finally, we argue that the characteristics, which Adorno ascribes to the work of art has migrated to, and been realised by, a form of protest which reemerged simultaneously with the death of Adorno, namely the riot

Haemodynamically significant plaque formation and regional endothelial dysfunction in cholesterol-fed ApoE

A B S T R A C T Flow-mediated vasodilation is suggested as one of the mechanisms involved in arterial expansive remodelling, which is thought to be a defence mechanism in atherogenesis. In the present study, we tested the hypothesis that lumen obstructive plaque formation is associated with failure of NO (nitric oxide)-dependent vasodilation in conduit vessels. Cardiac function and aortic root flow velocities were assessed using high-resolution echocardiography and two-dimensional-guided pulsed Doppler in ApoE −/− (apolipoprotein E-deficient) mice fed a standard or high-cholesterol diet. Endothelial function in the proximal and mid-descending aortic regions was studied using a myograph technique. Flow velocity at the aortic root of cholesterol-fed ApoE −/− mice was significantly increased as a result of lumen narrowing, detected via histological analysis. NO-dependent vasodilatory responses were selectively impaired in the atherosclerosis-prone vascular regions in cholesterol-fed ApoE −/− mice. In conclusion, consumption of a high-cholesterol diet results in lumen obstructive plaque formation in ApoE −/− mice, which significantly alters aortic root haemodynamics. This phenomenon is associated with impaired NO-dependent vasodilation in vessel segments known to be prone to atherosclerosis

Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking

Aims: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.Methods and results: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.Conclusions: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.</p

Self-control interventions for children under age 10 for improving self-control and delinquency and problem behaviors

Self-control improvement programs are intended to serve many purposes, most notably improving self-control. Yet, interventions such as these often aim to reduce delinquency and problem behaviors. However, there is currently no summary statement available regarding whether or not these programs are effective in improving self-control and reducing delinquency and problem behaviors. The main objective of this review is to assess the available research evidence on the effect of self-control improvement programs on self-control and delinquency and problem behaviors. In addition to investigating the overall effect of early selfcontrol improvement programs, this review will examine, to the extent possible, the context in which these programs may be most successful. The studies included in this systematic review indicate that self-control improvement programs are an effective intervention for improving self-control and reducing delinquency and problem behaviors, and that the effect of these programs appears to be rather robust across various weighting procedures, and across context, outcome source, and based on both published and unpublished data

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Imaging of coronary artery function and morphology in living mice - applications in atherosclerosis research

Atherosclerosis in the coronary arteries is the major reason for myocardial infarction and cardiovascular death. In the clinic, several imaging systems make it possible to study coronary artery function and morphology non-invasively, such as transthoracic Doppler echocardiography (TTDE). Coronary flow velocity reserve (CFVR), as assessed using TTDE, can be applied to detect early as well as late pathological changes in atherosclerotic disease. However, no imaging method has been capable of addressing coronary artery morphology and function in mouse, the most widely used experimental animal in cardiovascular disease. In this context, we set out to develop an ultrasound-based methodological platform to study coronary artery function and morphology and to explore how it could be used to confirm pathological cardiovascular changes in mouse. We showed that detection and measurements of left coronary artery (LCA) flow velocity in the proximal and more distal segments is feasible using TTDE. In order to measure coronary function, we introduced a CFVR protocol where coronary hyperemia was induced either by mild hypoxia or with adenosine. For the first time, we applied a novel ultrasound biomicroscopy (UBM) technique to morphologically measure atherosclerosis-related narrowing of coronary arteries and to detect adenosine-induced hyperemic dilatation of the LCA. Using a combination of TTDE and UBM, we were able to calculate a coronary flow index and thereby compare flow velocity-based CFVR and flow-based CFR in mouse. Using TTDE and UBM, we have been able to measure atherosclerosis-related changes measured as minimal lumen diameter (MLD) in the proximal LCA. In the absence of coronary stenosis, we showed that endotoxin reduced CFVR, and that some of the deleterious effects are mediated through the 5-lipoxygenase pathway. In another study, CFVR was found to co-vary with different inflammatory cytokines and atherosclerotic lesion characteristics at different time-points. In summary, we have developed a unique imaging platform to study mouse coronary artery function and morphology, and found that the established imaging read-outs appear to reflect important pathophysiological features of atherosclerosis