3,070 research outputs found

    Engaging political histories of urban uprisings with young people: The Liverpool riots, 1981 and 2011

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    Based on a participatory research project which involved academics and young people at KCC Live, a community radio station in Merseyside, exploring the 1981 and 2011 riots in Liverpool, UK, this paper argues that co-produced research involving young people and radio provides an under-utilised avenue for research on historical and political geographies. Working together for a year in 2012–13, the academic and non-academic participants produced a radio documentary exploring how and why the 1981 riots in Liverpool occurred, and what we could learn from those historical events to help understand the more recent 2011 riots. Young people’s capacities to engage with past events that took place before they were born, in order to reflect on and understand the political present, are seldom explored in research. The research that this paper is based on therefore provides an original and significant contribution to debates on conducting research with young people, in particular developing approaches to thinking through how young people engage with, and make sense of, politics and political activity, especially disruptive or insurgent activities like riots/urban uprisings. As a result, the paper makes an important contribution to work being done on the political capacities of young people; collective histories and memories in young people’s understandings of politics, place, and space; and knowledges of urban uprisings. We argue that bringing children’s/youth geographies into dialogue with political and historical geographies such as those discussed here is a useful avenue for future research. © The Author(s) 2020

    Rapid acceptability and adherence testing of a lipid-based nutrient supplement and a micronutrient powder among refugee children and pregnant and lactating women in Algeria

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    OBJECTIVE: To assess the acceptability and adherence to daily doses of lipid-based nutrient supplement (LNS) among children and micronutrient powder (MNP) among children and pregnant and lactating women. DESIGN: Household interviews and sachet counting were conducted to measure acceptability and adherence, 15 and 30 d after product distribution. Qualitative information on product acceptability was collected using focus group discussions. SETTING: Saharawi refugee camps, Algeria, August-October 2009. SUBJECTS: LNS was distributed to 123 children aged 6-35 months (LNS-C), and MNP to 112 children aged 36-59 months (MNP-C) and 119 pregnant or lactating women (MNP-W). RESULTS: At the end of the test 98·4 % of LNS-C, 90·4 % of MNP-C and 75·5 % of MNP-W participants reported that they liked the product (P<0·05). Other measures of acceptability did not differ. Median consumption of sachets was highest in the LNS-C group (P<0·001). 'Good' adherence to the daily regimen (consumption of 75-125 % of recommended dose) was 89·1 % in the LNS-C, compared with 57·0 % in the MNP-C and 65·8 % in the MNP-W groups (P<0·001). Qualitative findings supported the quantitative measures and guided selection of local product names, packaging designs, distribution mechanisms, and the design of the information campaign in the subsequent programme scale-up. CONCLUSIONS: Acceptability, consumption and adherence were higher in participants receiving LNS compared with MNP. However, both products were found to be suitable when compared with predefined acceptability criteria. Acceptability studies are feasible and important in emergency nutrition programmes when the use of novel special nutritional products is considered

    Challenges in Chagas Disease Drug Development.

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    The protozoan parasite Trypanosoma cruzi causes Chagas disease, an important public health problem throughout Latin America. Current therapeutic options are characterised by limited efficacy, long treatment regimens and frequent toxic side-effects. Advances in this area have been compromised by gaps in our knowledge of disease pathogenesis, parasite biology and drug activity. Nevertheless, several factors have come together to create a more optimistic scenario. Drug-based research has become more systematic, with increased collaborations between the academic and commercial sectors, often within the framework of not-for-profit consortia. High-throughput screening of compound libraries is being widely applied, and new technical advances are helping to streamline the drug development pipeline. In addition, drug repurposing and optimisation of current treatment regimens, informed by laboratory research, are providing a basis for new clinical trials. Here, we will provide an overview of the current status of Chagas disease drug development, highlight those areas where progress can be expected, and describe how fundamental research is helping to underpin the process

    HaloTag is an effective expression and solubilisation fusion partner for a range of fibroblast growth factors.

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    The production of recombinant proteins such as the fibroblast growth factors (FGFs) is the key to establishing their function in cell communication. The production of recombinant FGFs in E. coli is limited, however, due to expression and solubility problems. HaloTag has been used as a fusion protein to introduce a genetically-encoded means for chemical conjugation of probes. We have expressed 11 FGF proteins with an N-terminal HaloTag, followed by a tobacco etch virus (TEV) protease cleavage site to allow release of the FGF protein. These were purified by heparin-affinity chromatography, and in some instances by further ion-exchange chromatography. It was found that HaloTag did not adversely affect the expression of FGF1 and FGF10, both of which expressed well as soluble proteins. The N-terminal HaloTag fusion was found to enhance the expression and yield of FGF2, FGF3 and FGF7. Moreover, whereas FGF6, FGF8, FGF16, FGF17, FGF20 and FGF22 were only expressed as insoluble proteins, their N-terminal HaloTag fusion counterparts (Halo-FGFs) were soluble, and could be successfully purified. However, cleavage of Halo-FGF6, -FGF8 and -FGF22 with TEV resulted in aggregation of the FGF protein. Measurement of phosphorylation of p42/44 mitogen-activated protein kinase and of cell growth demonstrated that the HaloTag fusion proteins were biologically active. Thus, HaloTag provides a means to enhance the expression of soluble recombinant proteins, in addition to providing a chemical genetics route for covalent tagging of proteins

    Isolation and characterization of renin-like aspartic-proteases from Echis ocellatus venom

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    Three aspartic proteases (SVAPs) have been isolated from venom of the saw-scaled viper, Echis ocellatus. In confirmation of prior transcriptomic predictions, all three forms match to sequences of either of the two SVAP transcripts (EOC00051 and EOC00123), have a molecular weight of 42 kDa and possess a single N-glycan. The SVAPs act in a renin-like manner, specifically cleaving human and porcine angiotensinogen into angiotensin-1 and possess no general protease activity. Their activity is completely inhibited by the aspartyl protease inhibitor Pepstatin A

    Microsatellites for the marsh fritillary butterfly: de novo transcriptome sequencing, and a comparison with amplified fragment length polymorphism (AFLP) markers.

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    Journal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: Until recently the isolation of microsatellite markers from Lepidoptera has proved troublesome, expensive and time-consuming. Following on from a previous study of Edith's checkerspot butterfly, Euphydryas editha, we developed novel microsatellite markers for the vulnerable marsh fritillary butterfly, E. aurinia. Our goal was to optimize the process in order to reduce both time and cost relative to prevailing techniques. This was accomplished by using a combination of previously developed techniques: in silico mining of a de novo assembled transcriptome sequence, and genotyping the microsatellites found there using an economic method of fluorescently labelling primers. PRINCIPAL FINDINGS: In total, we screened nine polymorphic microsatellite markers, two of which were previously published, and seven that were isolated de novo. These markers were able to amplify across geographically isolated populations throughout Continental Europe and the UK. Significant deviations from Hardy-Weinberg equilibrium were evident in some populations, most likely due to the presence of null alleles. However, we used an F(st) outlier approach to show that these markers are likely selectively neutral. Furthermore, using a set of 128 individuals from 11 populations, we demonstrate consistency in population differentiation estimates with previously developed amplified fragment length polymorphism (AFLP) markers (r = 0.68, p<0.001). SIGNIFICANCE: Rapid development of microsatellite markers for difficult taxa such as Lepidoptera, and concordant results with other putatively neutral molecular markers, demonstrate the potential of de novo transcriptional sequencing for future studies of population structure and gene flow that are desperately needed for declining species across fragmented landscapes.BBSRCOkinawa Institute for Science and Technology (OIST

    A Full PFPF Shell Model Study of a~=~48 Nuclei

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    Exact diagonalizations with a minimally modified realistic force lead to detailed agreement with measured level schemes and electromagnetic transitions in 48^{48}Ca, 48^{48}Sc, 48^{48}Ti, 48^{48}V, 48^{48}Cr and 48^{48}Mn. Gamow-Teller strength functions are systematically calculated and reproduce the data to within the standard quenching factor. Their fine structure indicates that fragmentation makes much strength unobservable. As a by-product, the calculations suggest a microscopic description of the onset of rotational motion. The spectroscopic quality of the results provides strong arguments in favour of the general validity of monopole corrected realistic forces, which is discussed.Comment: 30 pages, LaTeX with epsf.sty, 14 Postscript figures included and compressed using uufiles. Completely new version of previous preprint nucl-th/9307001. FTUAM-93/01, CRN/PT 93-3

    Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease

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    BACKGROUND: Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. OBJECTIVES: We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. METHODS: We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using 23Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. RESULTS: CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = -0.5 ± 1.0 L; p = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4-31.3] vs. HC = 18.4 mmol/L [16.6-21.3]; p = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p = 0.26). Tissue sodium in both compartments correlated to FO (muscle: r = 0.63, p < 0.01; SC: rs = 0.63, p < 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p < 0.05), tumor necrosis factor-alpha (p < 0.01), and interleukin (IL)-6 (p = 0.01) and lower levels of vascular endothelial growth factor-C (p = 0.04). FO in CKD was linked to higher IL-8 (r = 0.51, p < 0.05) and inversely associated to E-selectin (r = -0.52, p = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p = 0.02). CONCLUSION: Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation

    Characterisation of the fumarate hydratase repertoire in Trypanosoma cruzi.

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    Nifurtimox and benznidazole represent the only treatments options available targeting Chagas disease, the most important parasitic infection in the Americas. However, use of these is problematic as they are toxic and ineffective against the more severe stages of the disease. In this work, we used a multidisciplinary approach to characterise the fumarases from Trypanosoma cruzi, the causative agent of Chagas Disease. We showed this trypanosome expresses cytosolic and mitochondrial fumarases that via an iron-sulfur cluster mediate the reversible conversion of fumarate to S-malate. Based on sequence, biochemical properties and co-factor binding, both T. cruzi proteins share characteristics with class I fumarases, enzymes found in bacteria and some other protozoa but absent from humans, that possess class II isoforms instead. Gene disruption suggested that although the cytosolic or mitochondrial fumarase activities are individually dispensable their combined activity is essential for parasite viability. Finally, based on the mechanistic differences with the human (host) fumarase, we designed and validated a selective inhibitor targeting the parasite enzyme. This study showed that T. cruzi fumarases should be exploited as targets for the development of new chemotherapeutic interventions against Chagas disease
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