| 1. |
- Alic, I., et al.
(författare)
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Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:10, s. 5766-5788
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Tidskriftsartikel (refereegranskat)abstract
- A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of beta-amyloid-(A beta)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar A beta deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome 21 gene BACE2, but prevented by combined chemical beta and gamma-secretase inhibition. We found that T21 organoids secrete increased proportions of A beta-preventing (A beta 1-19) and A beta-degradation products (A beta 1-20 and A beta 1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1 inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in similar to 30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases.
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| 2. |
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| 3. |
- Komm, M., et al.
(författare)
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Contribution to the multi-machine pedestal scaling from the COMPASS tokamak
- 2017
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Ingår i: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 57:5
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Tidskriftsartikel (refereegranskat)abstract
- First systematic measurements of pedestal structure during Ohmic and NBI-assisted Type I ELMy H-modes were performed on the COMPASS tokamak in two dedicated experimental campaigns during 2015 and 2016. By adjusting the NBI heating and a toroidal magnetic field, the electron pedestal temperature was increased from 200 eV up to 300 eV, which allowed reaching pedestal collisionality nu(ped)* < 1 at q(95) similar to 3. COMPASS has approached conditions for the Identity experiment done at JET & DIII-D, complementing the range of scanned rho(ped)*. The pedestal pressure was successfully reproduced by the EPED model. The dependence of pedestal pressure width on nu(ped)* and beta(pol)(ped) is discussed.
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| 4. |
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| 5. |
- Weinzettl, V., et al.
(författare)
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Dust remobilization experiments on the COMPASS tokamak
- 2017
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Ingår i: Fusion engineering and design. - : ELSEVIER SCIENCE SA. - 0920-3796 .- 1873-7196. ; 124, s. 446-449
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Tidskriftsartikel (refereegranskat)abstract
- Dust remobilization is one of the not yet fully understood mechanisms connected to the prompt erosion of material from plasma facing surfaces in fusion devices. As a part of a newly initiated cross-machine study, dust remobilization experiments have been performed on the COMPASS tokamak. Tungsten samples with well-defined deposited tungsten dust grains, prepared using a recently developed controlled pre-adhesion method, have been exposed to ELMy H-mode discharges as well as L-mode discharges with forced disruptions. Here we report on the technical aspects of the experiment realization as well as on the experimental results of dust remobilization. The latter is discussed in the light of data from other machines and a physical interpretation is suggested for the observed spatial localization of the dust remobilization activity. Evidence of rearrangement of isolated dust into clusters and strings is also presented.
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| 6. |
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| 7. |
- Bohm, P., et al.
(författare)
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Edge Thomson scattering diagnostic on COMPASS tokamak : Installation, calibration, operation, improvements
- 2014
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 85:11, s. 11E431-
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Tidskriftsartikel (refereegranskat)abstract
- The core Thomson scattering diagnostic (TS) on the COMPASS tokamak was put in operation and reported earlier. Implementation of edge TS, with spatial resolution along the laser beam up to similar to 1/100 of the tokamak minor radius, is presented now. The procedure for spatial calibration and alignment of both core and edge systems is described. Several further upgrades of the TS system, like a triggering unit and piezo motor driven vacuum window shutter, are introduced as well. The edge TS system, together with the core TS, is now in routine operation and provides electron temperature and density profiles.
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| 8. |
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| 10. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 11. |
- Pól, J., et al.
(författare)
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Spatial distribution of glycerophospholipids in the ocular lens
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge of the spatial distribution of lipids in the intraocular lens is important for understanding the physiology and biochemistry of this unique tissue and for gaining a better insight into the mechanisms underlying diseases of the lens. Following our previous study showing the spatial distribution of sphingolipids in the porcine lens, the current study used ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) to provide the whole lipidome of porcine lens and these studies were supplemented by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) of the lens using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) to determine the spatial distribution of glycerophospholipids. Altogether 172 lipid species were identified with high confidence and their concentration was determined. Sphingomyelins, phosphatidylcholines, and phosphatidylethanolamines were the most abundant lipid classes. We then determined the spatial and concentration-dependent distributions of 20 phosphatidylcholines, 6 phosphatidylethanolamines, and 4 phosphatidic acids. Based on the planar molecular images of the lipids, we report the organization of fiber cell membranes within the ocular lens and suggest roles for these lipids in normal and diseased lenses.
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| 12. |
- Zhao, Zhihong, et al.
(författare)
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Impact of stress on solute transport in a fracture network : A comparison study
- 2013
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Ingår i: Journal of Rock Mechanics and Geotechnical Engineering. - : Chinese Academy of Sciences. - 1674-7755. ; 5:2, s. 110-123
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Tidskriftsartikel (refereegranskat)abstract
- This paper compares numerical modeling of the effect of stress on solute transport (advection and matrix diffusion) in fractured rocks in which fracture apertures are correlated with fracture lengths. It is mainly motivated by the performance and safety assessments of underground radioactive waste repositories. Five research teams used different approaches to model stress/deformation, flow and transport processes, based on either discrete fracture network or equivalent continuum models. The simulation results derived by various teams generally demonstrated that rock stresses could significantly influence solute transport processes through stress-induced changes in fracture apertures and associated changes in permeability. Reasonably good agreement was achieved regarding advection and matrix diffusion given the same fracture network, while some observed discrepancies could be explained by different mechanical or transport modeling approaches.
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| 13. |
- Miörner, Håkan, et al.
(författare)
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Surface characteristics of group A streptococci with and without M-protein
- 1984
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Ingår i: Acta pathologica, microbiologica, et immunologica Scandinavica. Section B, Microbiology. - 0108-0180. ; 92:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Twenty M protein-positive and eight M protein-negative strains of group A streptococci were investigated with respect to surface hydrophobicity and amount of lipoteichoic acid (LTA). Surface hydrophobicity as determined in polymer two-phase systems varied substantially between individual strains and there was no correlation to the presence of antiphagocytic M protein. The amount of LTA on the surface of the bacteria varied with hydrophobic affinity of the cells. Strains with a high content of surface LTA were found among both M-positive and M-negative streptococci. Cellular and extracellular LTA was estimated on six strains by the ability of hot phenol extracts and culture fluids to sensitize erythrocytes and by rocket immunoelectrophoretic quantitation. Differences in content of surface LTA did not correlate to differences in the total amount of cellular LTA. Pepsin digestion of M-positive group A streptococci at suboptimal pH resulted in a loss of M antigen whereas surface LTA and the hydrophobic interaction liability was retained. The results indicate that the degree of surface hydrophobicity as measured by two-phase partitioning is not correlated to either the type-specific or the antiphagocytic moiety of M protein. The results support the correlation between surface LTA and surface hydrophobicity of group A streptococci.
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| 14. |
- Parma, Valentina, et al.
(författare)
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More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis
- 2020
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 45:7, s. 609-622
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Tidskriftsartikel (refereegranskat)abstract
- Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19–79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (−79.7 ± 28.7, mean ± standard deviation), taste (−69.0 ± 32.6), and chemesthetic (−37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
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