267 research outputs found

    Towards a framework for critical citizenship education

    Get PDF
    Increasingly countries around the world are promoting forms of "critical" citizenship in the planned curricula of schools. However, the intended meaning behind this term varies markedly and can range from a set of creative and technical skills under the label "critical thinking" to a desire to encourage engagement, action and political emancipation, often labelled "critical pedagogy". This paper distinguishes these manifestations of the "critical" and, based on an analysis of the prevailing models of critical pedagogy and citizenship education, develops a conceptual framework for analysing and comparing the nature of critical citizenship

    Groundwater Development in Arid Basins

    Get PDF
    Summary: Groundwater development frequently provides a means whereby tremendous new economic opportunities are opened up. If supplies are overdrawn (mined) the ensuing regional economy may be able to affort replacements from more costly sources. In the United States the Salt River Valley of Arizona and the valleys of California provide examples. Two cases are treated in this paper, Israel and West Pakistan. In Israel, besides furnishing more than half of the basic source of water suppply, groundwater development provides opportunity for both quantity and quality management, which makes possible use of surface supplies and reclaimed sewage as firm rather than marginal sources. This development will permit the total water resources of this small country, where agricultural production ranks among the world\u27s most efficient, to be utilized effectively down to almost the last drop by the mid 1970\u27s. Israel must then look to desalted water from the sea for further expansion of its overall water supply. In West Pakistan a combination of level terrain and leaky canals since about 1890 led to threatened waterlogging and salinity of more than 25 million acreas of irrigated land, even though supplies were less than half adequate for good productivity. By the 1950\u27s low yields and increasing population threatened starvation. However, initiation of groundwater development, first by the government and later by pricate entreprise, has, since 1960, let to construction of 3,500 governmental tube wells of about 3 cfs capacity and 30,000 private tube wells of slightly less than 1 cfs capacity. Results have been dramatic. Agricultural production and use of fertilizer are rapidly increasing, and opening of well development of pricate enterprise is providing the irrigator with benefits of free competition for his water custom which he did not previously enjoy. Ultimately, besides providing full supplies for an estimated 26 to 30 million acrea, drainage and salinity problems will be mitigated if about 50 million acre-feet are pumped each year from groundwater including about 28 million acre-feet to be mined from a reserve of about 1,900 million acre-feet. With some difficult surface storage development due to terrain, mining may eventually be reduced. Through an eventual technological solution for the continuing overdraft is not now in sight, perhaps an economy may be built which can affort such a solution when the time comes

    Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis

    Get PDF
    Background Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP. Methods Overall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups. Results Twelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls (P = 0.03 and 0.008, respectively). However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16–16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC. Conclusions We did not obtain evidence that CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts

    Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis

    Get PDF
    Objective: Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. Design: Intracellular calcium ([Ca2+]C), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. Results: Inhibition of OME with 4-MP converted predominantly transient [Ca2+]C rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. Conclusions: A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation

    Children’s rights online: challenges, dilemmas and emerging directions

    Get PDF
    In debates over internet governance, the interests of children figure unevenly, and only partial progress has been made in supporting children’s rights online globally. This chapter examines how the UN Convention on the Rights of the Child is helpful in mapping children’s rights to provision, protection and participation as they apply online as well as offline. However, challenges remain. First, opportunities and risks are positively linked, policy approaches are needed to resolve the potential conflict between protection on the one hand, and provision and participation on the other. Second, while parents may be relied on to some degree to balance their child’s rights and needs, the evidence suggests that a minority of parents are ill-equipped to manage this. Third, resolution is needed regarding the responsibility for implementing digital rights, since many governments prefer self-regulation in relation to internet governance. The chapter concludes by calling for a global governance body charged with ensuring the delivery of children’s rights

    Functional characterization of the human myosin-7a motor domain

    Get PDF
    Myosin-7a participates in auditory and visual processes. Defects in MYO7A, the gene encoding the myosin-7a heavy chain, are causative for Usher syndrome 1B, the most frequent cause of deaf-blindness in humans. In the present study, we performed a detailed kinetic and functional characterization of the isolated human myosin-7a motor domain to elucidate the details of chemomechanical coupling and the regulation of motor function. A rate-limiting, slow ADP release step causes long lifetimes of strong actin-binding intermediates and results in a high duty ratio. Moreover, our results reveal a Mg2+-sensitive regulatory mechanism tuning the kinetic and mechanical properties of the myosin-7a motor domain. We obtained direct evidence that changes in the concentration of free Mg2+ ions affect the motor properties of human myosin-7a using an in vitro motility assay system. Our results suggest that in a cellular environment, compartment-specific fluctuations in free Mg2+ ions can mediate the conditional switching of myosin-7a between cargo moving and tension bearing modes

    Glucose-6-Phosphate Dehydrogenase Protects Escherichia coli from Tellurite-Mediated Oxidative Stress

    Get PDF
    The tellurium oxyanion tellurite induces oxidative stress in most microorganisms. In Escherichia coli, tellurite exposure results in high levels of oxidized proteins and membrane lipid peroxides, inactivation of oxidation-sensitive enzymes and reduced glutathione content. In this work, we show that tellurite-exposed E. coli exhibits transcriptional activation of the zwf gene, encoding glucose 6-phosphate dehydrogenase (G6PDH), which in turn results in augmented synthesis of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Increased zwf transcription under tellurite stress results mainly from reactive oxygen species (ROS) generation and not from a depletion of cellular glutathione. In addition, the observed increase of G6PDH activity was paralleled by accumulation of glucose-6-phosphate (G6P), suggesting a metabolic flux shift toward the pentose phosphate shunt. Upon zwf overexpression, bacterial cells also show increased levels of antioxidant molecules (NADPH, GSH), better-protected oxidation-sensitive enzymes and decreased amounts of oxidized proteins and membrane lipids. These results suggest that by increasing NADPH content, G6PDH plays an important role in E. coli survival under tellurite stress

    Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP

    Get PDF
    Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease
    corecore