Exploiting the exploitable : The financialisation of students in English universities

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Disrupting actin filaments enhances glucose-stimulated insulin secretion independent of the cortical actin cytoskeleton

Just under the plasma membrane of most animal cells lies a dense meshwork of actin filaments called the cortical cytoskeleton. In insulin-secreting pancreatic β cells, a long-standing model posits that the cortical actin layer primarily acts to restrict access of insulin granules to the plasma membrane. Here we test this model and find that stimulating β cells with pro-secretory stimuli (glucose and/or KCl) has little impact on the cortical actin layer. Chemical perturbations of actin polymerization, by either disrupting or enhancing filamentation, dramatically enhance glucose-stimulated insulin secretion. Using scanning electron microscopy, we directly visualize the cortical cytoskeleton, allowing us to validate the effect of these filament-disrupting chemicals. We find the state of the cortical actin layer does not correlate with levels of insulin secretion, suggesting filament disruptors act on insulin secretion independently of the cortical cytoskeleton

Exploiting the exploitable: The financialisation of students in English universities

Funding sought by England’s universities from the private and unregulated capital market has produced significant change in the nature and functioning of their borrowing as they adapt to look attractive to and meet the requirements of their financiers. We suggest that the unregulated finance sector, part of the burgeoning number of financial intermediaries worldwide, is a de factomajor actor in the development of higher education in England – an influence iatrogenically enabled by government higher education policy. We focus on the complex interplay between government policy, universities, and financial intermediaries to reveal how processes of financialisation are now impacting university communities. Of particular concern are students, whose fees now constitute a securitised income stream for universities, from which they plan to repay their borrowings. As such, students have become securitised assets, their interests subservient to the need to ensure a steady income stream to satisfy private financiers. It follows that the public benefit mission and ethos of universities has also been undermined, possibly fatally

Comparison of a new multiplex real-time PCR with the Kato Katz thick smear and copro-antigen ELISA for the detection and differentiation of Taenia spp. in human stools

Background : Taenia solium, the cause of neurocysticercosis (NCC), has significant socioeconomic impacts on communities in developing countries. This disease, along with taeniasis is estimated to infect 2.5 to 5 million people globally. Control of T. solium NCC necessitates accurate diagnosis and treatment of T. solium taeniasis carriers. In areas where all three species of Taenia tapeworms (T. solium, Taenia saginata and Taenia asiatica) occur sympatrically, conventional microscope-and copro-antigen based diagnostic methods are unable to distinguish between these three Taenia species. Molecular diagnostic tools have been developed to overcome this limitation; however, conventional PCR-based techniques remain unsuitable for large-scale deployment in community-based surveys. Moreover, a real-time PCR (qPCR) for the discrimination of all three species of Taenia in human stool does not exist. This study describes the development and validation of a new triplex Taq-Man probe-based qPCR for the detection and discrimination of all three Taenia human tapeworms in human stools collected from communities in the Central Highlands of Vietnam. The diagnostic characteristics of the test are compared with conventional Kato Katz (KK) thick smear and copro-antigen ELISA (cAgELISA) method utilizing fecal samples from a community based cross-sectional study. Using this new multiplex real-time PCR we provide an estimate of the true prevalence of taeniasis in the source population for the community based cross-sectional study. Methodology/Principal findings : Primers and TaqMan probes for the specific amplification of T. solium, T. saginata and T. asiatica were designed and successfully optimized to target the internal transcribed spacer I (ITS-1) gene of T. solium and the cytochrome oxidase subunit I (COX-1) gene of T. saginata and T. asiatica. The newly designed triplex qPCR (T3qPCR) was compared to KK and cAgELISA for the detection of Taenia eggs in stool samples collected from 342 individuals in Dak Lak province, Central Highlands of Vietnam. The overall apparent prevalence of taeniasis in Dak Lak province was 6.72% (95% confidence interval (CI) [3.94-9.50]) in which T. solium accounted for 1.17% (95% CI [0.37-3.17]), according to the T3qPCR. There was sympatric presence of T. solium, T. saginata and T. asiatica. The T3qPCR proved superior to KK and cAgELISA for the detection and differentiation of Taenia species in human feces. Diagnostic sensitivities of 0.94 (95% credible interval (CrI) [0.88-0.98]), 0.82 (95% CrI [0.58-0.95]) and 0.52 (95% CrI [0.07-0.94]), and diagnostic specificities of 0.98 (95% CrI [0.94-1.00]), 0.91 (95% CrI [0.85-0.96]) and 0.99 (95% CrI [0.96-1.00]) were estimated for the diagnosis of taeniasis for the T3qPCR, cAgELISA and KK thick smear in this study, respectively. Conclusions : T3qPCR is not only superior to the KK thick smear and cAgELISA in terms of diagnostic sensitivity and specificity, but it also has the advantage of discriminating between species of Taenia eggs in stools. Application of this newly developed T3qPCR has identified the existence of all three human Taenia tapeworms in Dak Lak province and proves for the first time, the existence of T. asiatica in the Central Highlands and the south of Vietnam

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

GeV-Scale Thermal WIMPs: Not Even Slightly Dead

Weakly Interacting Massive Particles (WIMPs) have long reigned as one of the leading classes of dark matter candidates. The observed dark matter abundance can be naturally obtained by freezeout of weak-scale dark matter annihilations in the early universe. This "thermal WIMP" scenario makes direct predictions for the total annihilation cross section that can be tested in present-day experiments. While the dark matter mass constraint can be as high as $m_\chi\gtrsim100$ GeV for particular annihilation channels, the constraint on the total cross section has not been determined. We construct the first model-independent limit on the WIMP total annihilation cross section, showing that allowed combinations of the annihilation-channel branching ratios considerably weaken the sensitivity. For thermal WIMPs with s-wave $2\rightarrow2$ annihilation to visible final states, we find the dark matter mass is only known to be $m_\chi\gtrsim20$ GeV. This is the strongest largely model-independent lower limit on the mass of thermal-relic WIMPs, together with the upper limit on the mass from the unitarity bound ($m_\chi\lesssim 100$ TeV), it defines what we call the "WIMP window". To probe the remaining mass range, we outline ways forward.Comment: 16 pages, 10 figures, references added, accepted for publication in PR

A high-throughput in vivo micronucleus assay for genome instability screening in mice.

We describe a sensitive, robust, high-throughput method for quantifying the formation of micronuclei, markers of genome instability, in mouse erythrocytes. Micronuclei are whole chromosomes or chromosome segments that have been separated from the nucleus. Other methods of detection rely on labor-intensive, microscopy-based techniques. Here we describe a 2-d, 96-well plate-based flow cytometric method of micronucleus scoring that is simple enough for a research technician experienced in flow cytometry to perform. The assay detects low levels of genome instability that cannot be readily identified by classic phenotyping, using 25 μl of blood. By using this assay, we have screened >10,000 blood samples and discovered novel genes that contribute to vertebrate genome maintenance, as well as novel disease models and mechanisms of genome instability disorders. We discuss experimental design considerations, including statistical power calculation, we provide troubleshooting tips and we discuss factors that contribute to a false-positive increase in the number of micronucleated red blood cells and to experimental variability.Acknowledgments We thank M. Hitcham and N. Harman for assistance with blood collections, W. Cheng for assistance with flow cytometry during high-throughput screening and K. Dry for comments on the manuscript. R.E.M. is supported by Cancer Research UK (CRUK; project grant C20510/A12401). D.J.A. is supported by CRUK. D.J.A. and B.L.N. are supported by the Wellcome Trust. Research in the Jackson Laboratory is funded by CRUK program grant no. C6/A11224, the European Research Council and the European Community Seventh Framework Programme grant agreement no. HEALTH-F2-2010-259893 (DDResponse). Core funding is provided by CRUK (C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives his salary from the University of Cambridge, UK, supplemented by CRUK. G.B. is funded by CRUK program grant no. C6/A11224.This is the accepted manuscript for a paper published in Nature Protocols 10, 205–215 (2015) doi:10.1038/nprot.2015.010, Published online 31 December 201

Delayed presentation of symptomatic breast cancers in Hong Kong: Experience in a public cancer centre

Objective Delayed presentation is an important obstacle to improving cancer treatment outcomes. We aimed to study the magnitude of this problem in Hong Kong and the factors associated with delayed presentation of patients with symptomatic breast cancers. Design Retrospective study using self-administered questionnaires. Setting Clinical Oncology Department in a regional public hospital in Hong Kong. Patients A total of 158 Chinese women with breast cancer referred to our hospital between October 2006 and December 2007 consented to participate in this study. Among these, 59 (37%) patients were referred after having surgery in private sector. Results The mean total delay (from first symptom to treatment) was 22 weeks. The mean patient delay (from first symptom to first consultation) was 13 weeks, constituting the largest component (60%) of the total delay. After symptom onset, the delay exceeded 12 weeks for consulting a doctor in 29%, and for receipt of treatment in 52% of them. Low family income (<HK$5000 per month; P<0.001) and surgery in public hospitals (P=0.013) were both independent predictors of patient delay. Surgery in public hospitals (P=0.006) and low family income (P=0.005) were the only predictors of doctor/system delay and total delay, respectively. Conclusions Delayed presentation and treatment of symptomatic breast cancer remains an important issue in Hong Kong. Apart from socio-economic factors, limited access to public medical care was likely an important contributing factor in delays related to patients as well as to doctor/system.published_or_final_versio