E.P. Thompson and cultural sociology: questions of poetics, capitalism and the commons

There is currently a need for cultural sociology to readdress the work of humanistic and cultural Marxism. While more recently much of this work has been dismissed the appearance of more radical social movements and the on-going crisis of neoliberalism suggests that it still has much to tell us. In this respect, this article seeks to readdress the writing of historian E.P.Thompson arguing that his work on the class based and other social movements, poetics, critique of positivism and economic reason, utopia and work on the idea of the commons all has much to offer more contemporary scholarship. While the article recognises that the cultural Marxism of figures like Thompson can-not simply be resurrected it does continue to offer a number of critical insights lacking from other traditions within cultural sociology. By readdressing the internal complexity of Thompson’s writing the argumentative strategy of this article suggests that cultural sociology needs to move beyond more simplistic understandings of cultural Marxism and more carefully explore what it has to offer

An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Long-term outcomes after ablation of persistent atrial fibrillation: an observational study over 6 years.

ObjectivesTo address the limited long-term outcome data for catheter ablation (CA) of persistent atrial fibrillation (PeAF), we analysed consecutive ablations performed at our centre from 1 January 2008 to 31 December 2010 and followed patients prospectively until January 2014.MethodsBoth arrhythmia recurrence and symptom relief were assessed. Follow-up data were collected from hospital records, supplemented by data from general practitioners and referring hospitals. At the end of the follow-up period, all patients were contacted by phone to determine their up-to-date clinical condition.Results188 consecutive patients with PeAF (157 male, mean age 57.3±9.7 years, 20% with long-standing PeAF) underwent a mean of 1.75 procedures (range 1-4). Telephone follow-up was achieved for 77% of surviving patients. Over a mean follow-up of 46±16 months (range 4-72), 139 (75%) patients experienced arrhythmia recurrence after a single procedure and 90 (48%) after their final procedure. Median time to first recurrence was 210 days (range 91-1850). 71% of recurrences were within the first year following ablation and 91% within 2 years. At final follow-up, 82% of patients reported symptomatic improvement. 7 (2.3%) major complications occurred, and there was no procedure-related death or stroke.ConclusionsCA for PeAF is safe with a low rate of complications. Over a follow-up period of up to 6 years, a large majority of patients experience significant symptomatic improvement but recurrence after the initial procedure is the norm rather than the exception. 2 years' follow-up is sufficient to observe 90% of AF recurrences, but recurrence can occur even after 5 years' remission

Delineating Astrocytic Cytokine Responses in a Human Stem Cell Model of Neural Trauma

Neuroinflammation has been shown to mediate the pathophysiological response following traumatic brain injury (TBI). Accumulating evidence implicates astrocytes as key immune cells within the central nervous system (CNS), displaying both pro- and anti-inflammatory properties. The aim of this study was to investigate how in vitro human astrocyte cultures respond to cytokines across a concentration range that approximates the aftermath of human TBI. To this end, enriched cultures of human induced pluripotent stem cell (iPSC)-derived astrocytes were exposed to interleukin-1β (IL-1β) (1–10,000 pg/mL), IL-4 (1–10,000 pg/mL), IL-6 (100–1,000,000 pg/mL), IL-10 (1–10,000 pg/mL) and tumor necrosis factor (TNF)-α (1–10,000 pg/mL). After 1, 24, 48 and 72 h, cultures were fixed and immunolabeled, and the secretome/supernatant was analyzed at 24, 48, and 72 h using a human cytokine/chemokine 39-plex Luminex assay. Data were compared to previous in vitro studies of neuronal cultures and clinical TBI studies. The secretome revealed concentration-, time- and/or both concentration- and time-dependent production of downstream cytokines (29, 21, and 17 cytokines, respectively, p<0.05). IL-1β exposure generated the most profound downstream response (27 cytokines), IL-6 and TNF had intermediate responses (13 and 11 cytokines, respectively), whereas IL-4 and IL-10 only led to weak responses over time or in escalating concentration (8 and 8 cytokines, respectively). Notably, expression of IL-1β, IL-6, and TNF cytokine receptor mRNA was higher in astrocyte cultures than in neuronal cultures. Several secreted cytokines had temporal trajectories, which corresponded to those seen in the aftermath of human TBI. In summary, iPSC-derived astrocyte cultures exposed to cytokine concentrations reflecting those in TBI generated an increased downstream cytokine production, particularly IL-1β. Although more work is needed to better understand how different cells in the CNS respond to the neuroinflammatory milieu after TBI, our data shows that iPSC-derived astrocytes represent a tractable model to study cytokine stimulation in a cell type-specific manner

Astrocytes display cell autonomous and diverse early reactive states in familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a rapidly progressive and fatal disease. Although astrocytes are increasingly recognized contributors to the underlying pathogenesis, the cellular autonomy and uniformity of astrocyte reactive transformation in different genetic forms of amyotrophic lateral sclerosis remain unresolved. Here we systematically examine these issues by using highly enriched and human induced pluripotent stem cell-derived astrocytes from patients with VCP and SOD1 mutations. We show that VCP mutant astrocytes undergo cell-autonomous reactive transformation characterized by increased expression of complement component 3 (C3) in addition to several characteristic gene expression changes. We then demonstrate that isochronic SOD1 mutant astrocytes also undergo a cell-autonomous reactive transformation, but that this is molecularly distinct from VCP mutant astrocytes. This is shown through transcriptome-wide analyses, identifying divergent gene expression profiles and activation of different key transcription factors in SOD1 and VCP mutant human induced pluripotent stem cell-derived astrocytes. Finally, we show functional differences in the basal cytokine secretome between VCP and SOD1 mutant human induced pluripotent stem cell-derived astrocytes. Our data therefore reveal that reactive transformation can occur cell autonomously in human amyotrophic lateral sclerosis astrocytes and with a striking degree of early molecular and functional heterogeneity when comparing different disease-causing mutations. These insights may be important when considering astrocyte reactivity as a putative therapeutic target in familial amyotrophic lateral sclerosis

The Moral Economy of Heroin in ‘Austerity Britain’

This article presents the findings of an ethnographic exploration of heroin use in a disadvantaged area of the United Kingdom. Drawing on developments in continental philosophy as well as debates around the nature of social exclusion in the late-modern west, the core claim made here is that the cultural systems of exchange and mutual support which have come to underpin heroin use in this locale—that, taken together, form a ‘moral economy of heroin’—need to be understood as an exercise in reconstituting a meaningful social realm by, and specifically for, this highly marginalised group. The implications of this claim are discussed as they pertain to the fields of drug policy, addiction treatment, and critical criminological understandings of disenfranchised groups

The global politics of a ‘poncy pillowcase’: Migration and borders in Coronation Street

This article examines the ways in which popular culture stages and supplies resources for agency in everyday life, with particular attention to migration and borders. Drawing upon cultural studies, and specific insights originating from the Birmingham Centre for Contemporary Cultural Studies, we explore how intersectional identities such as race, ethnicity, class, and gender are experienced in relation to the globalisation of culture and identity in a 2007 Coronation Street storyline. The soap opera genre offers particular insights into how agency emerges in everyday life as migrants and locals navigate the forces of globalisation. We argue that a focus on popular culture can mitigate the problem of isolating migrant experiences from local experiences in migrant-receiving areas

Chandrasekhar-Kendall functions in astrophysical dynamos

Some of the contributions of Chandrasekhar to the field of magnetohydrodynamics are highlighted. Particular emphasis is placed on the Chandrasekhar-Kendall functions that allow a decomposition of a vector field into right- and left-handed contributions. Magnetic energy spectra of both contributions are shown for a new set of helically forced simulations at resolutions higher than what has been available so far. For a forcing function with positive helicity, these simulations show a forward cascade of the right-handed contributions to the magnetic field and nonlocal inverse transfer for the left-handed contributions. The speed of inverse transfer is shown to decrease with increasing value of the magnetic Reynolds number.Comment: 10 pages, 5 figures, proceedings of the Chandrasekhar Centenary Conference, to be published in PRAMANA - Journal of Physic

Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

Role of cardiac mitofusins in cardiac conduction following simulated ischemia–reperfusion

Mitochondrial dysfunction induced by acute cardiac ischemia–reperfusion (IR), may increase susceptibility to arrhythmias by perturbing energetics, oxidative stress production and calcium homeostasis. Although changes in mitochondrial morphology are known to impact on mitochondrial function, their role in cardiac arrhythmogenesis is not known. To assess action potential duration (APD) in cardiomyocytes from the Mitofusins-1/2 (Mfn1/Mfn2)-double-knockout (Mfn-DKO) compared to wild-type (WT) mice, optical-electrophysiology was conducted. To measure conduction velocity (CV) in atrial and ventricular tissue from the Mfn-DKO and WT mice, at both baseline and following simulated acute IR, multi-electrode array (MEA) was employed. Intracellular localization of connexin-43 (Cx43) at baseline was evaluated by immunohistochemistry, while Cx-43 phosphorylation was assessed by Western-blotting. Mfn-DKO cardiomyocytes demonstrated an increased APD. At baseline, CV was significantly lower in the left ventricle of the Mfn-DKO mice. CV decreased with simulated-ischemia and returned to baseline levels during simulated-reperfusion in WT but not in atria of Mfn-DKO mice. Mfn-DKO hearts displayed increased Cx43 lateralization, although phosphorylation of Cx43 at Ser-368 did not differ. In summary, Mfn-DKO mice have increased APD and reduced CV at baseline and impaired alterations in CV following cardiac IR. These findings were associated with increased Cx43 lateralization, suggesting that the mitofusins may impact on post-MI cardiac-arrhythmogenesis