'Concrete freedom' : C.L.R. James on culture and black politics

This article aims to provide a synoptic account of the cultural writings of the West Indian intellectual and activist C.L.R. James. I aim to make a case for greater recognition of his work among cultural sociologists. I go on to show how James’ original, historicising account of cultural forms relates closely to his wider political interventions including, specifically, his ground-breaking discussion of mid-twentieth century black politics in America

“Artlift” Arts-on-Referral Intervention in UK Primary Care: Updated findings from an ongoing observational study

Background: Arts for health interventions are an accepted option for medical management of mental wellbeing in health care. Updated findings are presented from a prospective longitudinal follow-up (observational) design study of an arts on referral programme in UK general practice, over a 7-year period (2009–2016). Methods: Primary care process and mental wellbeing outcomes were investigated, including progress through the intervention, changes in mental wellbeing, and factors associated with those outcomes. A total of n =1297 patients were referred to an eight or 10-week intervention over a period from 2009 to 2016. Patient sociodemographic information was recorded at baseline, and patient progress (e.g. attendance) assessed throughout the intervention. Results: Of all referrals, 51.7% completed their course of prescribed art (the intervention). Of those that attended, 74.7% engaged with the intervention as rated by the artists leading the courses. A significant increase in wellbeing was observed from pre- to post-intervention (t = −19.29, df =523, P < 0.001, two-tailed) for those that completed and/or engaged. A sub sample (N =103) of these referrals self-reported multi-morbidities. These multiple health care service users were majority completers (79.6%), and were rated as having engaged (81.0%). This group also had a significant increase in well-being, although this was smaller than for the group as a whole (t = −7.38, df =68, P < 0.001). Conclusion: Findings confirm that art interventions can be effective in the promotion of well-being for those that complete, including those referred with multi-morbidity, with significant changes in wellbeing evident across the intervention periods

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Representations of sport in the revolutionary socialist press in Britain, 1988–2012

This paper considers how sport presents a dualism to those on the far left of the political spectrum. A long-standing, passionate debate has existed on the contradictory role played by sport, polarised between those who reject it as a bourgeois capitalist plague and those who argue for its reclamation and reformation. A case study is offered of a political party that has consistently used revolutionary Marxism as the basis for its activity and how this party, the largest in Britain, addresses sport in its publications. The study draws on empirical data to illustrate this debate by reporting findings from three socialist publications. When sport did feature it was often in relation to high profile sporting events with a critical tone adopted and typically focused on issues of commodification, exploitation and alienation of athletes and supporters. However, readers’ letters, printed in the same publications, revealed how this interpretation was not universally accepted, thus illustrating the contradictory nature of sport for those on the far left

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Syntactic comprehension deficits across the FTD-ALS continuum

To establish the frequency, severity, relationship to bulbar symptoms, and neural correlates of syntactic comprehension deficits across the frontotemporal dementia–amyotrophic lateral sclerosis (FTD-ALS) disease spectrum. In total, 85 participants were included in the study; 20 amyotrophic lateral sclerosis (ALS), 15 FTD-ALS, 27 progressive nonfluent aphasia (PNFA), and 23 controls. Syntactic comprehension was evaluated in ALS, FTD-ALS, PNFA, and controls using the Test for Reception of Grammar. Voxel-based morphometry examined neuroanatomical correlates of performance. Syntactic comprehension deficits were detected in 25% of ALS (p = 0.011), 92.9% of FTD-ALS (p < 0.001), and 81.5% of PNFA (p < 0.001) patients. FTD-ALS was disproportionately impaired compared to PNFA. Impaired Test for Reception of Grammar performance was frequent in ALS with early bulbar involvement but did not correlate with bulbar impairment overall. Left peri-insular atrophy correlated with syntactic comprehension deficits. Syntactic comprehension deficits are frequent in FTD-ALS, more severe than in PNFA, and related to left peri-insular atrophy. A significant minority of ALS patients are impaired, but the relationship between bulbar symptoms and syntactic impairment is not understood

Revisiting histories of anti-racist thought and activism

This piece reconsiders histories of anti-racist thought and practice, including the linkages between anti-racisms and other traditions of liberatory thought. We argue that anti-racism should be understood as a strand in radical thought linking internationalism, institutional critique and street activism, in the process interfeeding with other social movements. The traditions of anti-racist thought discussed in this special issue exemplify these cross-cutting influences