2,057 research outputs found

    Ordinary Lives

    Get PDF

    Monitoring the impact of land reform on quality of life: A South African case study

    Get PDF
    In 1994, the first democratically elected government of South Africa committed itself to the Reconstruction and Development Programme (RDP), the policy framework through which it was hoped, a broad transformation of South African society could be achieved. The overal

    Monitoring the impact of land reform on quality of life : a South African case study.

    Get PDF
    Accepted for publication by Social Indicators Research 58: 293–312, 2002.This paper outlines the approach that is utilized by the Monitoring and Evaluation directorate of the Department of Land Affairs (DLA) in South Africa in assessing the quality of life for the land Reform beneficiaries. The paper begins with an overview of the three Land Reform programs in South Africa. The paper then moves on to outline the original design for monitoring and evaluating the quality of life for land reform beneficiaries. It then proceeds to detail the current Monitoring and Evaluation design being utilized, highlighting its strengths and weaknesses. The last section discusses some of the findings of the quality of life study undertaken in 1999

    Identification of the active site of legumain links it to caspases, clostripain and gingipains in a new clan of cysteine endopeptidases

    Get PDF
    AbstractWe show by site-directed mutagenesis that the catalytic residues of mammalian legumain, a recently discovered lysosomal asparaginycysteine endopeptidase, form a catalytic dyad in the motif His-Gly-spacer-Ala-Cys. We note that the same motif is present in the caspases, aspartate-specific endopeptidases central to the process of apoptosis in animal cells, and also in the families of clostripain and gingipain which are arginyl/lysyl endopeptidases of pathogenic bacteria. We propose that the four families have similar protein folds, are evolutionarily related in clan CD, and have common characteristics including substrate specificities dominated by the interactions of the S1 subsite

    Structure-based finite strain modelling of the human left ventricle in diastole

    Get PDF
    Finite strain analyses of the left ventricle provide important information on heart function and have the potential to provide insights into the biomechanics of myocardial contractility in health and disease. Systolic dysfunction is the most common cause of heart failure; however, abnormalities of diastolic function also contribute to heart failure, and are associated with conditions including left ventricular hypertrophy and diabetes. The clinical significance of diastolic abnormalities is less well understood than systolic dysfunction, and specific treatments are presently lacking. To obtain qualitative and quantitative information on heart function in diastole, we develop a three-dimensional computational model of the human left ventricle that is derived from noninvasive imaging data. This anatomically realistic model has a rule-based fibre structure and a structure-based constitutive model. We investigate the sensitivity of this comprehensive model to small changes in the constitutive parameters and to changes in the fibre distribution. We make extensive comparisons between this model and similar models that employ different constitutive models, and we demonstrate qualitative and quantitative differences in stress and strain distributions for the different constitutive models. We also provide an initial validation of our model through comparisons to experimental data on stress and strain distributions in the left ventricle

    The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

    Get PDF
    The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

    Proteomics Portrait of Archival Lesions of Chronic Pancreatitis

    Get PDF
    Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL), mild chronic pancreatitis (MCP), severe chronic pancreatitis (SCP) and pancreatic ductal adenocarcinoma (PDAC) were subjected to proteomic analysis using a “label-free” comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma
    corecore