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Sökning: WFRF:(Fabian Alexander)

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11.
  • MacKenzie, Alison, et al. (författare)
  • Dissolving the Dichotomies Between Online and Campus-Based Teaching : a Collective Response to The Manifesto for Teaching Online (Bayne et al. 2020)
  • 2022
  • Ingår i: Postdigital Science and Education. - : Springer. - 2524-4868 .- 2524-485X. ; 4, s. 271-329
  • Tidskriftsartikel (refereegranskat)abstract
    • This article is a collective response to the 2020 iteration of The Manifesto for Teaching Online. Originally published in 2011 as 20 simple but provocative statements, the aim was, and continues to be, to critically challenge the normalization of education as techno-corporate enterprise and the failure to properly account for digital methods in teaching in Higher Education. The 2020 Manifesto continues in the same critically provocative fashion, and, as the response collected here demonstrates, its publication could not be timelier. Though the Manifesto was written before the Covid-19 pandemic, many of the responses gathered here inevitably reflect on the experiences of moving to digital, distant, online teaching under unprecedented conditions. As these contributions reveal, the challenges were many and varied, ranging from the positive, breakthrough opportunities that digital learning offered to many students, including the disabled, to the problematic, such as poor digital networks and access, and simple digital poverty. Regardless of the nature of each response, taken together, what they show is that The Manifesto for Teaching Online offers welcome insights into and practical advice on how to teach online, and creatively confront the supremacy of face-to-face teaching.
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14.
  • Roemer, Sebastian N., et al. (författare)
  • Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies
  • 2024
  • Ingår i: BRAIN. - 0006-8950 .- 1460-2156. ; 147:7, s. 2428-2439
  • Tidskriftsartikel (refereegranskat)abstract
    • Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies.We included 51 A beta-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5-2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres.As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion.Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity. Four-repeat tauopathies are rapidly progressive neurodegenerative diseases with mixed subcortical and cortical symptoms. Using advanced neuroimaging methods, Roemer et al. show that subcortical tau accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions.
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15.
  • Rönn, Tina, et al. (författare)
  • Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by β-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1, FOXP1, GABRA2, GLR1A, RHOT1, and TBC1D4. We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1-deficiency in β-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca2+, and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1-deficient β-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets.
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16.
  • Sikkema, Lisa, et al. (författare)
  • An integrated cell atlas of the lung in health and disease
  • 2023
  • Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
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17.
  • Zhou Hagström, Nanna, 1993-, et al. (författare)
  • Megahertz-rate Ultrafast X-ray Scattering and Holographic Imaging at the European XFEL
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The advent of X-ray free-electron lasers (XFELs) has revolutionized fundamental science, from atomic to condensed matter physics, from chemistry to biology, giving researchers access to X-rays with unprecedented brightness, coherence, and pulse duration. All XFEL facilities built until recently provided X-ray pulses at a relatively low repetition rate, with limited data statistics. Here, we present the results from the first megahertz repetition rate X-ray scattering experiments at the Spectroscopy and Coherent Scattering (SCS) instrument of the European XFEL. We illustrate the experimental capabilities that the SCS instrument offers, resulting from the operation at MHz repetition rates and the availability of the novel DSSC 2D imaging detector. Time-resolved magnetic X-ray scattering and holographic imaging experiments in solid state samples were chosen as representative examples, providing an ideal test-bed for operation at megahertz rates. Nevertheless, our results are relevant and applicable to any other non-destructive XFEL experiments in the soft X-ray range. 
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18.
  • Zhou Hagström, Nanna, 1993-, et al. (författare)
  • Megahertz-rate ultrafast X-ray scattering and holographic imaging at the European XFEL
  • 2022
  • Ingår i: Journal of Synchrotron Radiation. - : International Union of Crystallography (IUCr). - 0909-0495 .- 1600-5775. ; 29, s. 1454-1464
  • Tidskriftsartikel (refereegranskat)abstract
    • The advent of X-ray free-electron lasers (XFELs) has revolutionized fundamental science, from atomic to condensed matter physics, from chemistry to biology, giving researchers access to X-rays with unprecedented brightness, coherence and pulse duration. All XFEL facilities built until recently provided X-ray pulses at a relatively low repetition rate, with limited data statistics. Here, results from the first megahertz-repetition-rate X-ray scattering experiments at the Spectroscopy and Coherent Scattering (SCS) instrument of the European XFEL are presented. The experimental capabilities that the SCS instrument offers, resulting from the operation at megahertz repetition rates and the availability of the novel DSSC 2D imaging detector, are illustrated. Time-resolved magnetic X-ray scattering and holographic imaging experiments in solid state samples were chosen as representative, providing an ideal test-bed for operation at megahertz rates. Our results are relevant and applicable to any other non-destructive XFEL experiments in the soft X-ray range.
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19.
  • Zuntini, Alexandre R., et al. (författare)
  • Phylogenomics and the rise of the angiosperms
  • 2024
  • Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
  • Tidskriftsartikel (refereegranskat)abstract
    • Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
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20.
  • Abé, Christoph, et al. (författare)
  • Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.
  • 2022
  • Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 91:6, s. 582-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD.Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables.Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18
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