1,506 research outputs found

    No good surprises: intending lecturers' preconceptions and initial experiences of further education

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    Current initiatives to promote lifelong learning and a broader inclusiveness in post-16 education have focused attention on further education (FE). The article examines the experiences and reactions of 41 intending lecturers studying full-time for a Postgraduate Certificate in Further Education and Training (PGCET), as they enter FE colleges on teaching practice and encounter FE students for the first time. It argues that the sector may have something to learn from the contrast between these intending lecturers' expectations and their subsequent experiences, and that attempts to address problems which are endemic within the current FE sector by initiatives to improve teacher competence, such as the Further Education National Training Organisation (FENTO)'s recently introduced FE teacher training standards, are inadequate and misdirected

    Spatial and Seasonal Distribution of American Whaling and Whales in the Age of Sail

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    American whalemen sailed out of ports on the east coast of the United States and in California from the 18th to early 20th centuries, searching for whales throughout the world’s oceans. From an initial focus on sperm whales (Physeter macrocephalus) and right whales (Eubalaena spp.), the array of targeted whales expanded to include bowhead whales (Balaena mysticetus), humpback whales (Megaptera novaeangliae), and gray whales (Eschrichtius robustus). Extensive records of American whaling in the form of daily entries in whaling voyage logbooks contain a great deal of information about where and when the whalemen found whales. We plotted daily locations where the several species of whales were observed, both those caught and those sighted but not caught, on world maps to illustrate the spatial and temporal distribution of both American whaling activity and the whales. The patterns shown on the maps provide the basis for various inferences concerning the historical distribution of the target whales prior to and during this episode of global whaling

    Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration

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    Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic 'gain of function', such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases

    Microbiological Evaluation of Water Quality from Urban Watersheds for Domestic Water Supply Improvement

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    Agricultural and urban runoffs may be major sources of pollution of water bodies and major sources of bacteria affecting the quality of drinking water. Of the different pathways by which bacterial pathogens can enter drinking water, this one has received little attention to date; that is, because soils are often considered to be near perfect filters for the transport of bacterial pathogens through the subsoil to groundwater. The goals of this study were to determine the distribution, diversity, and antimicrobial resistance of pathogenic Escherichia coli isolates from low flowing river water and sediment with inputs from different sources before water is discharged into ground water and to compare microbial contamination in water and sediment at different sampling sites. Water and sediment samples were collected from 19 locations throughout the watershed for the isolation of pathogenic E. coli. Heterotrophic plate counts and E. coli were also determined after running tertiary treated water through two tanks containing aquifer sand material. Presumptive pathogenic E. coli isolates were obtained and characterized for virulent factors and antimicrobial resistance. None of the isolates was confirmed as Shiga toxin E. coli (STEC), but as others, such as enterotoxigenic E. coli (ETEC). Pulsed field gel electrophoresis (PFGE) was used to show the diversity E. coli populations from different sources throughout the watershed. Seventy six percent of the isolates from urban sources exhibited resistance to more than one antimicrobial agent. A subsequent filtration experiment after water has gone through filtration tanks containing aquifer sand material showed that there was a 1 to 2 log reduction in E. coli in aquifer sand tank. Our data showed multiple strains of E. coli without virulence attributes, but with high distribution of resistant phenotypes. Therefore, the occurrence of E. coli with multiple resistances in the environment is a matter of great concern due to possible transfer of resistant genes from nonpathogenic to pathogenic strains that may result in increased duration and severity of morbidity

    Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration

    Get PDF
    Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic ‘gain of function’, such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases

    AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

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    <p>Abstract</p> <p>Background</p> <p>The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD.</p> <p>Methods</p> <p>Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP.</p> <p>Results</p> <p>Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination.</p> <p>Conclusion</p> <p>We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.</p

    Development and validation of the Arizona Cognitive Test Battery for Down syndrome

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    Neurocognitive assessment in individuals with intellectual disabilities requires a well-validated test battery. To meet this need, the Arizona Cognitive Test Battery (ACTB) has been developed specifically to assess the cognitive phenotype in Down syndrome (DS). The ACTB includes neuropsychological assessments chosen to 1) assess a range of skills, 2) be non-verbal so as to not confound the neuropsychological assessment with language demands, 3) have distributional properties appropriate for research studies to identify genetic modifiers of variation, 4) show sensitivity to within and between sample differences, 5) have specific correlates with brain function, and 6) be applicable to a wide age range and across contexts. The ACTB includes tests of general cognitive ability and prefrontal, hippocampal and cerebellar function. These tasks were drawn from the Cambridge Neuropsychological Testing Automated Battery (CANTAB) and other established paradigms. Alongside the cognitive testing battery we administered benchmark and parent-report assessments of cognition and behavior. Individuals with DS (n = 74, ages 7–38 years) and mental age (MA) matched controls (n = 50, ages 3–8 years) were tested across 3 sites. A subsample of these groups were used for between-group comparisons, including 55 individuals with DS and 36 mental age matched controls. The ACTB allows for low floor performance levels and participant loss. Floor effects were greater in younger children. Individuals with DS were impaired on a number ACTB tests in comparison to a MA-matched sample, with some areas of spared ability, particularly on tests requiring extensive motor coordination. Battery measures correlated with parent report of behavior and development. The ACTB provided consistent results across contexts, including home vs. lab visits, cross-site, and among individuals with a wide range of socio-economic backgrounds and differences in ethnicity. The ACTB will be useful in a range of outcome studies, including clinical trials and the identification of important genetic components of cognitive disability

    Uukuniemi Phlebovirus Assembly and Secretion Leave a Functional Imprint on the Virion Glycome

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    Uukuniemi virus (UUKV) is a model system for investigating the genus Phlebovirus of the Bunyaviridae. We report the UUKV glycome, revealing differential processing of the Gn and Gc virion glycoproteins. Both glycoproteins display poly-N-acetyllactosamines, consistent with virion assembly in the medial Golgi apparatus, whereas oligomannose-type glycans required for DC-SIGN-dependent cellular attachment are predominant on Gc. Local virion structure and the route of viral egress from the cell leave a functional imprint on the phleboviral glycome
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