Challenging the empire

This paper considers how Paul Gilroy transformed hitherto dominant understandings of the relationship between race and class by developing an innovative account that foregrounded questions of racist oppression and collective resistance amid the organic crisis of British capitalism. The returns from this rethinking were profound in that he was able to make transparent both the structuring power of racism within the working class, and the necessity for autonomous black resistance. At the same time, significant lacunae in his account are identified, including the neglect of the episodic emergence of working-class anti-racism and the part played by socialists, particularly those of racialized minority descent in fashioning a major anti-racist social movement. The paper concludes with a lament for the disappearance of such work informed by a ‘Marxism without guarantees’ in the contemporary field of racism studies, and asks readers to consider the gains to be derived from such a re-engagement

A systematic review of primary Sjögren’s syndrome in male and paediatric populations

Primary Sjögren’s syndrome (pSS) is a chronic multisystem autoimmune rheumatic disease characterised by female predominance. Although the disease is rare in the male and paediatric populations, it has been suggested that it may have a different disease phenotype, which has not been investigated before using a systematic approach. A systematic literature search of PubMed databases (updated to December 2016) was performed to identify all published data on the epidemiological, clinical and laboratory manifestations of pSS in the male and paediatric populations. The literature search of the male and paediatric pSS studies identified 2025 and 186 citations, respectively, out of which 7 and 5 fulfilled our inclusion criteria and were analysed further. The range of age at disease onset was 9.4–10.7 years for children and 39.4–56.9 years at diagnosis for male patients. We identified a prevalence of extra-glandular manifestations between 52.6–92.3% in the male population and 50.0–84.6% in children, while abnormal sialometry was only reported in the paediatric population, with a prevalence between 71.4 and 81.8%. There was a significant variation of positive serological markers, with anti-Ro antibodies reported between 15.7–75.0% and 36.4–84.6%, and anti-La antibodies between 5.6–51.7% and 27.3–65.4%, in the male and paediatric populations, respectively. The characteristics of pSS in the male and paediatric populations varied according to different studies. When compared to data available from pSS adult populations, children diagnosed with pSS reported less dryness and had a higher prevalence of parotitis, lymphadenopathy and systemic symptoms and male patients were younger at the time of diagnosis. This systematic review contributes to a better understanding of the epidemiology of pSS in rare populations. Large longitudinal cohort studies comparing male with female patients and adult with paediatric patients are needed

Herschel-SPIRE-Fourier Transform Spectroscopy of the nearby spiral galaxy IC342

We present observations of the nearby spiral galaxy IC342 with the Herschel Spectral and Photometric Imaging Receiver (SPIRE) Fourier Transform Spectrometer. The spectral range afforded by SPIRE, 196-671 microns, allows us to access a number of 12CO lines from J=4--3 to J=13--12 with the highest J transitions observed for the first time. In addition we present measurements of 13CO, [CI] and [NII]. We use a radiative transfer code coupled with Bayesian likelihood analysis to model and constrain the temperature, density and column density of the gas. We find two 12CO components, one at 35 K and one at 400 K with CO column densities of 6.3x10^{17} cm^{-2} and 0.4x10^{17} cm^{-2} and CO gas masses of 1.26x10^{7} Msolar and 0.15x10^{7} Msolar, for the cold and warm components, respectively. The inclusion of the high-J 12CO line observations, indicate the existence of a much warmer gas component (~400 K) confirming earlier findings from H_{2} rotational line analysis from ISO and Spitzer. The mass of the warm gas is 10% of the cold gas, but it likely dominates the CO luminosity. In addition, we detect strong emission from [NII] 205microns and the {3}P_{1}->{3}P_{0} and {3}P_{2} ->{3}P_{1} [CI] lines at 370 and 608 microns, respectively. The measured 12CO line ratios can be explained by Photon-dominated region (PDR) models although additional heating by e.g. cosmic rays cannot be excluded. The measured [CI] line ratio together with the derived [C] column density of 2.1x10^{17} cm^{-2} and the fact that [CI] is weaker than CO emission in IC342 suggests that [CI] likely arises in a thin layer on the outside of the CO emitting molecular clouds consistent with PDRs playing an important role.Comment: 9 pages, 8 figures, accepted for publication in Monthly Notices of the Royal Astronomical Society (MNRAS

Photocrosslinking Activity-Based Probes for Ubiquitin RING E3 Ligases

Summary: Activity-based protein profiling is an invaluable technique for studying enzyme biology and facilitating the development of therapeutics. Ubiquitin E3 ligases (E3s) are one of the largest enzyme families and regulate a host of (patho)physiological processes. The largest subtype are the RING E3s of which there are >600 members. RING E3s have adaptor-like activity that can be subject to diverse regulatory mechanisms and have become attractive drug targets. Activity-based probes (ABPs) for measuring RING E3 activity do not exist. Here we re-engineer ubiquitin-charged E2 conjugating enzymes to produce photocrosslinking ABPs. We demonstrate activity-dependent profiling of two divergent cancer-associated RING E3s, RNF4 and c-Cbl, in response to their native activation signals. We also demonstrate profiling of endogenous RING E3 ligase activation in response to epidermal growth factor (EGF) stimulation. These photocrosslinking ABPs should advance E3 ligase research and the development of selective modulators against this important class of enzymes

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory.

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.The authors’ research is funded by the Wellcome Trust (grant number 086871/Z/08/Z), the MRC (G0701500), a joint award from the MRC (G1000183) and Wellcome Trust (093875/Z/10/ Z) in support of the Behavioral and Clinical Neuroscience Institute at Cambridge University, and an MRC strategic award to the Imperial College-Cambridge University-Manchester University (ICCAM) addiction cluster (G1000018).This is the final version of the article. It first appeared from Springer at http://dx.doi.org/10.1007/s00213-016-4405-8

The influence of irrigant activation, concentration and contact time on sodium hypochlorite penetration into root dentine: an ex vivo experiment

Aim To establish if irrigant activation techniques, namely manual‐dynamic‐activation (MDA), passive‐ultrasonic‐irrigation (PUI) and sonic‐irrigation (SI), improve the tubular penetration of sodium hypochlorite (NaOCl) into root dentine when compared with conventional‐needle‐irrigation (CNI). Secondly, investigate if increasing NaOCl concentration and/or contact‐time improves the performance of these techniques. Methodology A total of 83 extracted human maxillary permanent canines were decoronated to 15 mm and root canals prepared to a size 40,.10 taper. Root dentine was stained with crystal violet for 72 h and embedded in silicone. Eighty specimens were randomly distributed into 16 groups (n = 5) according to the irrigant activation technique, NaOCl concentration (2%; 5.25%) and irrigant contact‐time (10 min; 20 min). All activation techniques were used for 60 s in the last minute of irrigation. Additionally, 3 teeth were not exposed to NaOCl to confirm adequate dentine staining had occurred (i.e. negative control). All specimens were subsequently dissected, observed under a light microscope and NaOCl penetration depth (µm) determined by measuring the average width of bleached dentine using ImageJ software. Statistical comparisons were made with paired and unpaired t‐tests, ANOVAs followed by post‐hoc Tukey and Dunnett’s tests, and a general linear model (α < 0.05). Results Overall, NaOCl penetration ranged from 38.8 µm – 411.0 µm with MDA, PUI and SI consistently resulting in significantly greater tubular infiltration than CNI (P < 0.05). The deepest measurements in the coronal, middle and apical segments were all recorded in the MDA; 5.25%; 20 min group and the least in the CNI; 2%; 10 min group. Increasing either irrigant concentration or contact‐time resulted in significantly greater NaOCl penetration depths for all techniques and segments of the canal (P < 0.05). However, when irrigant concentration and contact‐time were increased together, a significant interaction effect between these two independent variables was observed on overall NaOCl penetration (P < 0.05). Conclusions Agitating irrigants with MDA, PUI or SI, as well as using greater irrigant concentrations or contact‐times, potentiated NaOCl penetration into root dentine. However, longer durations of NaOCl exposure at lower concentrations resulted in similar depths of tubular penetration as those achieved at higher concentrations

Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke--Blood Pressure) randomised controlled trial.

OBJECTIVE: To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. DESIGN: Open label randomised controlled trial. SETTING: 99 general practices in England, with participants recruited in 2009-11. PARTICIPANTS: People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. INTERVENTIONS: Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. MAIN OUTCOME MEASURE: Change in systolic blood pressure between baseline and 12 months. RESULTS: 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). CONCLUSIONS: Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure.Trial registration Current Controlled Trials ISRCTN29062286.This report is independent research funded by the National Institute for Health Research (Stroke Prevention in Primary Care, Programme Grant for Applied Research, RP-PG-0606-1153), and by an NIHR Professorship (Prof McManus). FDRH is part funded as Director of the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR), Theme Leader of the NIHR Oxford Biomedical Research Centre (BRC), and Director of the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Oxford. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS. The study sponsor was the University of Birmingham. The study funder and sponsor had no role in the study design, collection, analysis or interpretation of data, in the writing of the report, or in the decision to submit to publication. The researchers are independent of the funders.This is the final version of the article. It first appeared from the BMJ Publishing Group via http://dx.doi.org/10.1136/bmj.i70

Herschel-ATLAS/GAMA: A difference between star formation rates in strong-line and weak-line radio galaxies

We have constructed a sample of radio-loud objects with optical spectroscopy from the Galaxy and Mass Assembly (GAMA) project over the Herschel Astrophysical Terahertz Large Area Survey (Herschel-ATLAS) Phase 1 fields. Classifying the radio sources in terms of their optical spectra, we find that strong-emission-line sources ('high-excitation radio galaxies') have, on average, a factor of ~4 higher 250-μm Herschel luminosity than weak-line ('lowexcitation') radio galaxies and are also more luminous than magnitude-matched radio-quiet galaxies at the same redshift. Using all five H-ATLAS bands, we show that this difference in luminosity between the emission-line classes arises mostly from a difference in the average dust temperature; strong-emission-line sources tend to have comparable dust masses to, but higher dust temperatures than, radio galaxies with weak emission lines. We interpret this as showing that radio galaxies with strong nuclear emission lines are much more likely to be associated with star formation in their host galaxy, although there is certainly not a one-to-one relationship between star formation and strong-line active galactic nuclei (AGN) activity. The strong-line sources are estimated to have star formation rates at least a factor of 3-4 higher than those in the weak-line objects. Our conclusion is consistent with earlier work, generally carried out using much smaller samples, and reinforces the general picture of high-excitation radio galaxies as being located in lower-mass, less evolved host galaxies than their low-excitation counterparts.Peer reviewe

Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases

The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct, and its physiological importance is emerging. Here, we couple chemically and chemoenzymatically synthesized ubiquitinated lysine and threonine model substrates to a mass spectrometry-based DUB assay. Using this platform, we profile two-thirds of known catalytically active DUBs for threonine esterase and lysine isopeptidase activity and find that most DUBs demonstrate dual selectivity. However, with two anomalous exceptions, the ovarian tumor domain DUB class demonstrates specific (iso)peptidase activity. Strikingly, we find the Machado–Joseph disease (MJD) class to be unappreciated non-lysine DUBs with highly specific ubiquitin esterase activity rivaling the efficiency of the most active isopeptidases. Esterase activity is dependent on the canonical catalytic triad, but proximal hydrophobic residues appear to be general determinants of non-lysine activity. Our findings also suggest that ubiquitin esters have appreciable cellular stability and that non-lysine ubiquitination is an integral component of the ubiquitin system. Its regulatory sophistication is likely to rival that of canonical ubiquitination.We thank Axel Knebel, Richard Ewan, Clare Johnson, and Daniel Fountaine from the Medical Research Council (MRC) Protein Production and Assay Development team, and MRC Reagents and Services, who all contributed to the generation of protein reagents required for the MALDI-TOF DUB assay platform. We thank Ronald Hay for provision of the plasmid encoding the constitutively active RNF4 E3 ligase. This work was funded by the United Kingdom MRC (MC_UU_12016/8), the Biotechnology and Biological Sciences Research Council (BB/P003982/1), and The Michael J. Fox Foundation (12756). We also acknowledge pharmaceutical companies supporting the Division of Signal Transduction Therapy (Boehringer-Ingelheim, GlaxoSmithKline, and Merck KGaA).Peer reviewe