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Sökning: LAR1:oru > Kungliga Tekniska Högskolan

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1.
  • Abrahamsson, Thomas, et al. (författare)
  • Low diversity of the gut microbiota in infants with atopic eczema
  • 2012
  • Ingår i: Journal of Allergy and Clinical Immunology. - New York, USA : Elsevier BV. - 0091-6749 .- 1097-6825. ; 129:2, s. 434-U244
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. OBJECTIVE: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. METHODS: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). RESULTS: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P= .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P= .02 and P= .01) and the phylum Proteobacteria at 12 months of age (P= .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R edgeR test: P= .008, q= 0.02). CONCLUSION: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.
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2.
  • Abrahamsson, Thomas, et al. (författare)
  • Low gut microbiota diversity in early infancy precedes asthma at school age
  • 2014
  • Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:6, s. 842-850
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.
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4.
  • Agélii Genlott, Annika, 1968-, et al. (författare)
  • Disseminating digital innovation in school : leading second-order educational change
  • 2019
  • Ingår i: Education and Information Technologies. - : Springer. - 1360-2357 .- 1573-7608. ; 24:5, s. 3021-3039
  • Tidskriftsartikel (refereegranskat)abstract
    • Using digital technology effectively in schools requires profound changes in traditional teaching and learning activities. Pedagogical innovations often start small-scale and developing good ideas into shared practice across schools is challenging in many ways, especially if the innovation requires second-order change, i.e. challenges to fundamental beliefs about teaching and learning. This study investigates how a validated pedagogical method requiring integrated Information and Communication Technology (ICT) use and second-order change can be disseminated and sustained over time. We surveyed 92 primary school teachers who at different times over a 5-year period participated in a training course designed to implement an innovative technology-supported teaching method, Write To Learn, across an entire city. We found that organized teacher development programs can drive second-order change, but this requires considerable, active, and sustained effort from leaders at both school and district level. Additional factors include immediate and extended social systems and handling diversity among teachers. The results are useful for both practitioners and researchers since they contribute to a deeper understanding of the opportunities and challenges involved in disseminating effective ICT-based methods that requires profound changes of thinking about teaching and learning to guide the transformation of teaching practice.
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5.
  • Agélii Genlott, Annika, 1968-, et al. (författare)
  • Leading dissemination of digital, science-based innovation in school–a case study
  • 2021
  • Ingår i: Interactive Learning Environments. - : Informa UK Limited. - 1049-4820 .- 1744-5191. ; , s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Digitalizing school is a process that comes with challenges. It requires strategic leadership and transformational change to work processes. Nevertheless, some succeed, and it is useful to understand what makes for success. This paper studies the challenges of leading digitalization of education in a city which decided to implement an IT-supported method for teaching literacy in primary schools. The method required transformational change; teachers not only had to learn to use technologies, they also had to review their pedagogy. This study is guided by the Diffusion of Innovation theory and draws on interviews with school principals. We find that the critical factors relate to the communication channel, the social system within and across schools, and the time perspective.
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6.
  • Ahlberg, Ernst, et al. (författare)
  • Using conformal prediction to prioritize compound synthesis in drug discovery
  • 2017
  • Ingår i: Proceedings of Machine Learning Research. - Stockholm : Machine Learning Research. ; , s. 174-184
  • Konferensbidrag (refereegranskat)abstract
    • The choice of how much money and resources to spend to understand certain problems is of high interest in many areas. This work illustrates how computational models can be more tightly coupled with experiments to generate decision data at lower cost without reducing the quality of the decision. Several different strategies are explored to illustrate the trade off between lowering costs and quality in decisions.AUC is used as a performance metric and the number of objects that can be learnt from is constrained. Some of the strategies described reach AUC values over 0.9 and outperforms strategies that are more random. The strategies that use conformal predictor p-values show varying results, although some are top performing.The application studied is taken from the drug discovery process. In the early stages of this process compounds, that potentially could become marketed drugs, are being routinely tested in experimental assays to understand the distribution and interactions in humans.
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7.
  • Alijagic, Andi, 1992-, et al. (författare)
  • A Novel Nanosafety Approach Using Cell Painting, Metabolomics, and Lipidomics Captures the Cellular and Molecular Phenotypes Induced by the Unintentionally Formed Metal-Based (Nano)Particles
  • 2023
  • Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.
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8.
  • Andersson, Johanna, et al. (författare)
  • Comparison of steaming and boiling of root vegetables for enhancing carbohydrate content and sensory profile
  • 2022
  • Ingår i: Journal of Food Engineering. - : Elsevier BV. - 0260-8774 .- 1873-5770. ; 312
  • Tidskriftsartikel (refereegranskat)abstract
    • Root vegetables have unique techno-functional and nutritional properties however, their use in processed foods is limited to a few species, partially due to a lack of knowledge related to the impact of thermal treatments on the sensory properties. This study investigated the effect of steaming and boiling on the microstructure, mechanical properties, and sensory profile of three model root vegetables with distinct carbohydrate composition: Jerusalem artichoke (Helianthus tuberosus L.), parsnip (Pastinaca sativa), and beetroot (Beta vulgaris). Thermally treated Jerusalem artichoke and parsnip showed higher content of cell wall polysaccharides, particularly β-glucans (e.g. cellulose) and pectic components, compared to raw. Steaming produced more cell shrinkage and loss of cell-cell adhesion than boiling, leading to softer vegetables. Processed beetroot showed loss of cell turgor and drastic softening but not clear changes in overall carbohydrate content. The scores for several flavour and in-mouth attributes were higher for steamed vegetables compared to boiled. Our results give insights on the processability of root vegetables towards products with enhanced sensory and nutritional properties.
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9.
  • Andersson, Linda, 1973, et al. (författare)
  • Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:43, s. 4481-4492
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function.METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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