37 research outputs found

    Programutbildningar pÄ distans - Erfarenhetsutbyte och utvÀrdering

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    The aim of this project has been to survey the advantages and problems that arise when a programme is transformed from being a campus education to a distance education. The paper is based on experiences gained during discussions in the project group and on the results from two surveys answered by programme coordinators from more than 20 universities in Sweden. By sharing experiences the members of the project group have been more successful in their work to improve distance education and support other teachers during planning and realization. The experiences from distance education have a positive effect on campus education. The project group found that it is very important to share experiences and discuss how to realize a successful distance education; forums for discussion must be created. The paper ends with recommendations and matters to consider when starting a distance programme. Examination process must be adapted to distance education (i.e. net based examination, virtual oral examination). Increase the use of synchronous communication to enhance collaborative learning. Develop a common policy for how distance education should be carried out and disseminate it among all teachers and students (i.e. response time, handling of examination, compulsory meetings). Facilitate possibilities for students to change from a distance program to a campus based program and vice versa. Facilitate planed flexibilities to make it easier for students that want to combine studies with work (life long learning)

    Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia : a case report

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    Background Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD. However, it is unknown whether there is a common genetic cause to DD and laterality defects or ciliopathies. Case presentation Here, we studied two individuals with co-occurring situs inversus (SI) and DD using whole genome sequencing to identify genetic variants of importance for DD and SI. Individual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). Both variants are predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified. Conclusions We identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD and further studies into the association between laterality, ciliopathies and DD are needed.Peer reviewe

    Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

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    We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue

    Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

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    We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue

    The clinical significance of inflammatory cytokines in primary cell culture in endometrial carcinoma

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    Endometrial cancer is the most common malignancy of the female genital tract, and the incidence and mortality rates from this disease are increasing. Although endometrial carcinoma has been regarded as a tissue‐specific disease mediated by female sex steroid pathways, considerable evidence implicates a role for an inflammatory response in the development and propagation of endometrial cancer. We hypothesized that if specific patterns of cytokine expression were found to be predictive of adverse outcome, then selective receptor targeting may be a therapeutic option. This study was therefore undertaken to determine the relationship between cytokine production in primary cell culture and clinical outcome in endometrial adenocarcinoma. Fresh endometrial tissues were fractionated into epithelial and stromal fractions and cultured. After 6–7 days, supernatants were collected and cells enumerated. Batched aliquots were assayed using ELISA kits specific for CSF‐1, GMCSF, G‐CSF, TNF‐α, IL‐6, IL‐8, and VEGF. Data were compared using ANOVA, Fisher's exact, and log rank tests. Increased epithelial VEGF production was observed more often in tumors with Type 2 variants (p = 0.039) and when GPR30 receptor expression was high (p = 0.038). Although increased stromal VEGF production was detected more often in grade 3 endometrioid tumors (p = 0.050), when EGFR expression was high (p = 0.003), and/or when ER/PR expression was low (p = 0.048), VEGF production did not correlated with overall survival (OS). Increased epithelial CSF‐1 and TNF‐α production, respectively, were observed more often in tumors with deep myometrial invasion (p = 0.014) and advanced stage (p = 0.018). Increased CSF‐1 (89.5% vs. 42.9%, p = 0.032), TNF‐α (88.9% vs. 42.9%, p = 0.032, and IL‐6 (92.3% vs. 61.5%, p = 0.052) also correlated with low OS. In Cox multivariate models, CSF‐1 was an independent predictor of low survival when stratified by grade (p = 0.046) and histology (p = 0.050), and TNF‐α, when stratified by histology (p = 0.037). In this study, high CSF‐1, TNF‐α, and IL‐6 production rates identified patients at greatest risk for death, and may signify patients likely to benefit from receptor‐specific therapy

    Studies of Tight Junctions and Airway Surface Liquid in Airway Epithelium with Relevance to Cystic Fibrosis

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    Cystic fibrosis (CF) is a multi-organ autosomal recessive disease of fluid-transporting epithelia, due to a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is a cAMP-regulated Cl-channel involved in various regulatory processes. Salt and water transport depend on CFTR and the epithelial sodium channel (ENaC), operating in concert with the paracellular pathway through the tight junctions (TJ). The ionic composition of the ASL has been assumed to be altered in CF, resulting in a fatal accumulation of viscous mucus in the airways. ASL samples were collected from tracheal and nasal fluid in normal and transgenic CF mice and from the fluid covering the apical surface of normal bronchial cells (16HBE14o-) and a CF human bronchial cell line (CFBE41o-). Analysis of the elemental content of the ASL was performed by X-ray microanalysis. The ASL contained more Na and Cl in CFTR-deficient or DF508-CFTR-containing cells than in control cells with wild- type CFTR. The relation between osmolarity and TJ permeability was examined by the addition of salt or sugar (295-700 mOsm) to 16HBE14o- cells, where the integrity of TJ was evaluated by transepithelial electrical resistance (TEER) measurements. Studies of interaction between the activity of CFTR, TJ and cytoskeleton were performed in CFBE41o-, plasmid corrected CFBE41o- (CFBE41o pCep4), and 16HBE14o- cells exposed to an inhibitor of CFTR (CFTRinh-172). The TJ were investigated by determining the paracellular permeability to lanthanum ions or with [14C] mannitol. Cytoskeletal changes were evaluated by immunofluorescence. Hyperosmotic stress resulted in opening of TJ. Inhalation of hypertonic salt or sugar solutions may open TJ, leading to enhanced paracellular water transport and increased ASL volume, diluted mucus and enhanced mucociliary clearance. This may explain the beneficial effect of this treatment for CF-patients. In healthy airway epithelial cells, inhibition of CFTR by CFTRinh-172 resulted in an increased TEER, whereas stimulation of CFTR by IBMX/forskolin caused a decrease. The paracellular permeability was inversely proportional to TEER. Immunofluorescence revealed a disorganization of cytoskeletal proteins in CF-cells. These results point toward a possible interaction between the activity of CFTR and TJ protein complex, presumably via the cytoskeleton

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    Decarbonising Economies

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    Based on an interdisciplinary investigation of future visions, scenarios, and case-studies of low carbon innovation taking place across economic domains, Decarbonising Economies analyses the ways in which questions of agency, power, geography and materiality shape the conditions of possibility for a low carbon future. It explores how and why the challenge of changing our economies are variously ascribed to a lack of finance, a lack of technology, a lack of policy and a lack of public engagement, and shows how the realities constraining change are more fundamentally tied to the inertia of our existing high carbon society and limited visions for what a future low carbon world might become. Through showcasing the first seeds of innovation seeking to enable transformative change, Decarbonising Economies will also chart a course for future research and policy action towards our climate goals. This title is also available as Open Access on Cambridge Core

    IdrottslÀraren som kulturbÀrare - dÄ, nu och i framtiden

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    Rapport frÄn Nordisk idrottslÀrarkongress, 4-9 augusti, 2009, Grebbestads folkhögskol
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