| 1. |
- Gao, YX, et al.
(författare)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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| 2. |
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| 3. |
- Willasch, AM, et al.
(författare)
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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
- 2020
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 55:98, s. 1540-1551
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Tidskriftsartikel (refereegranskat)abstract
- Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2–18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective “real-world-practice” study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
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| 4. |
- Ljungman, P., et al.
(författare)
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Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry
- 2023
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Ingår i: FRONTIERS IN IMMUNOLOGY. - : Frontiers Media SA. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionCOVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. MethodsThis study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. ResultsThe median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. DiscussionAlthough the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.
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| 5. |
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| 6. |
- Lankester, Arjan C, et al.
(författare)
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Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006-2014 European cohort.
- 2022
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 149:5
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome.We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome.HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed.Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P<.001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P< .001). Genetic subgroups did not differ in 2-year OS (P= .1) and EFS (P=.073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor-deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5×10e3/μL at+1 year were identified as independent predictors of favorable clinical and immunologic outcome.Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.
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| 7. |
- Biber, H., et al.
(författare)
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Sputtering Behavior of Rough, Polycrystalline Mercury Analogs
- 2022
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Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- The solar wind continuously impacts on rocky bodies in space, eroding their surface, thereby contributing significantly to the exosphere formations. The BepiColombo mission to Mercury will investigate the Hermean exosphere, which makes an understanding of the precise formation processes crucial for evaluation of the acquired data. We therefore developed an experimental setup with two microbalances that allows us to compare the sputter behavior of deposited thin solid layers with that of real mineral samples in the form of pressed powder. In addition, this technique is used to study the angular distribution of the sputtered particles. Using 4 keV He+ and 2 keV Ar+ ions, the sputter behavior of pellets of the minerals enstatite (MgSiO3) and wollastonite (CaSiO3) is studied, because these minerals represent analogs for the surface of the planet Mercury or the Moon. Pellets of powdered enstatite show significantly lower sputter yields than thin amorphous enstatite films prepared by pulsed laser deposition. 3D simulations of sputtering based on surface topography data from atomic force microscopy show that the observed reduction can be explained by the much rougher pellet surface alone. We therefore conclude that sputter yields from amorphous thin films can be applied to surfaces of celestial bodies exposed to ion irradiation, provided the effects of surface roughness, as encountered in realistic materials in space, are adequately accounted for. This also implies that taking surface roughness into account is important for modeling of the interaction of the solar wind with the surface of Mercury.
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| 8. |
- Binder, Eva, 1990-, et al.
(författare)
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Temperature-Dependent Behavior of Mature Cement Paste : Creep Testing and Multiscale Modeling
- 2023
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Ingår i: International RILEM Conference on Synergising Expertise towards Sustainability and Robustness of Cement-based Materials and Concrete Structures. SynerCrete 2023. - : Springer. - 9783031332104 - 9783031332111 ; , s. 171-180
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Konferensbidrag (refereegranskat)abstract
- The elastic compliance of cementitious materials increases slightly, and their time-dependent “creep” compliance increases significantly with increasing temperature. The present contribution provides quantitative insight into this topic. Thereby, the focus rests on mature cement paste made from Ordinary Portland cement and distilled water. Macroscopic creep experiments were performed, in order to quantify both elastic and creep moduli in the range of temperatures from 20 ℃ to 45 ℃. The experimental results regarding temperature-dependent values of the modulus of elasticity are validated herein using original results from ultrasonics testing. Finally, a multiscale model was used to establish a link to well-known stiffness constants of unhydrated cement clinker, as well as to temperature-dependent elastic and creep stiffness properties of nanoscopic hydrate-gel needles.
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| 9. |
- Binder, Eva, 1990-, et al.
(författare)
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Thermally activated viscoelasticity of cement paste : Minute-long creep tests and micromechanical link to molecular properties
- 2023
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Ingår i: Cement and Concrete Research. - : Elsevier. - 0008-8846 .- 1873-3948. ; 163
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Tidskriftsartikel (refereegranskat)abstract
- The stiffness of cementitious materials decreases with increasing temperature. Herein, macroscopic samples of mature cement pastes are subjected at 20, 30, and 45 degrees C, respectively, to three-minutes-long creep compression experiments. The test evaluation is based on the linear theory of viscoelasticity and Boltzmann's superposition principle. This yields macroscopic elastic and creep moduli as a function of temperature. A state-of-the-art multiscale model for creep homogenization of cement paste is extended to account for temperature-dependent elastic and creep moduli of the hydrate gel. This extension is based on results from published molecular simulations. Temperature-independent stiffness is assumed for cement clinker. Upscaling to the macroscale of cement paste yields elastic and creep moduli which agree well with the aforementioned experimental results. The Arrhenius-type activation energy of the creep modulus is found to be independent of scale, composition, and maturity, because of ineffective stress redistributions from creeping to non-creeping constituents.
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| 10. |
- Maresova, A., et al.
(författare)
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Improved syntheses of P2X(7) ligands based on substituted benzyl amide of pyroglutamic acid motif labelled with iodine-123 or iodine-125
- 2023
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Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - 0236-5731.
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Tidskriftsartikel (refereegranskat)abstract
- P2X(7) sites are emerging targets for molecular imaging research, notably in the context of neurodegeneration and inflammatory conditions. Therefore, we prepared a precursor for (radio)iodination of the P2X(7) ligand VPGIS191. We then developed a radioiodination method with I-123 for SPECT with a radiochemical yield of 71 +/- 13% and I-125 for autoradiography with a radiochemical yield of 85 +/- 6% Autoradiography of [I-125]VPGIS191 in mouse brain cryostat sections demonstrated approximately 36 nM binding affinity and B-max of approximately 400 pmol/gram tissue for P2X(7) binding sites. VPGIS191 (cis) had a two-fold lower affinity compared to its geometric trans-isomer TZ6019.
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| 11. |
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| 12. |
- Sebastiani, Federica, et al.
(författare)
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Apolipoprotein E Binding Drives Structural and Compositional Rearrangement of mRNA-Containing Lipid Nanoparticles
- 2021
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:4, s. 6709-6722
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Tidskriftsartikel (refereegranskat)abstract
- Emerging therapeutic treatments based on the production of proteins by delivering mRNA have become increasingly important in recent times. While lipid nanoparticles (LNPs) are approved vehicles for small interfering RNA delivery, there are still challenges to use this formulation for mRNA delivery. LNPs are typically a mixture of a cationic lipid, distearoylphosphatidylcholine (DSPC), cholesterol, and a PEG-lipid. The structural characterization of mRNA-containing LNPs (mRNA-LNPs) is crucial for a full understanding of the way in which they function, but this information alone is not enough to predict their fate upon entering the bloodstream. The biodistribution and cellular uptake of LNPs are affected by their surface composition as well as by the extracellular proteins present at the site of LNP administration, e.g., apolipoproteinE (ApoE). ApoE, being responsible for fat transport in the body, plays a key role in the LNP’s plasma circulation time. In this work, we use small-angle neutron scattering, together with selective lipid, cholesterol, and solvent deuteration, to elucidate the structure of the LNP and the distribution of the lipid components in the absence and the presence of ApoE. While DSPC and cholesterol are found to be enriched at the surface of the LNPs in buffer, binding of ApoE induces a redistribution of the lipids at the shell and the core, which also impacts the LNP internal structure, causing release of mRNA. The rearrangement of LNP components upon ApoE incubation is discussed in terms of potential relevance to LNP endosomal escape.
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| 13. |
- Waldie, Sarah, et al.
(författare)
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Lipoprotein ability to exchange and remove lipids from model membranes as a function of fatty acid saturation and presence of cholesterol.
- 2020
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier. - 1388-1981 .- 1879-2618. ; 1865:10
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Tidskriftsartikel (refereegranskat)abstract
- Lipoproteins play a central role in the development of atherosclerosis. High and low-density lipoproteins (HDL and LDL), known as 'good' and 'bad' cholesterol, respectively, remove and/or deposit lipids into the artery wall. Hence, insight into lipid exchange processes between lipoproteins and cell membranes is of particular importance in understanding the onset and development of cardiovascular disease. In order to elucidate the impact of phospholipid tail saturation and the presence of cholesterol in cell membranes on these processes, neutron reflection was employed in the present investigation to follow lipid exchange with both HDL and LDL against model membranes. Mirroring clinical risk factors for the development of atherosclerosis, lower exchange was observed in the presence of cholesterol, as well as for an unsaturated phospholipid, compared to faster exchange when using a fully saturated phospholipid. These results highlight the importance of membrane composition on the interaction with lipoproteins, chiefly the saturation level of the lipids and presence of cholesterol, and provide novel insight into factors of importance for build-up and reversibility of atherosclerotic plaque. In addition, the correlation between the results and well-established clinical risk factors suggests that the approach taken can be employed also for understanding a broader set of risk factors including, e.g., effects of triglycerides and oxidative stress, as well as local effects of drugs on atherosclerotic plaque formation.
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| 14. |
- Ahmadi, Delaram, et al.
(författare)
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Nanoscale Structure and Dynamics of Model Membrane Lipid Raft Systems, Studied by Neutron Scattering Methods
- 2022
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Ingår i: Frontiers in Physics. - : Frontiers Media SA. - 2296-424X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quasi-elastic neutron scattering (QENS) and small angle neutron scattering (SANS), in combination with isotopic contrast variation, have been used to determine the structure and dynamics of three-component lipid membranes, in the form of vesicles, comprising an unsaturated [palmitoyl-oleoyl-phosphatidylcholine (POPC) or dioleoyl-phosphatidylcholine (DOPC)], a saturated phospholipid (dipalmitoyl-phosphatidylcholine (DPPC)), and cholesterol, as a function temperature and composition. SANS studies showed vesicle membranes composed of a 1:1:1 molar ratio of DPPC:DOPC:cholesterol and a 2:2:1 molar ratio of DPPC:POPC:cholesterol phase separated, forming lipid rafts of ∼18 and ∼7 nm diameter respectively, when decreasing temperature from 308 to 297 K. Phase separation was reversible upon increasing temperature. The larger rafts observed in systems containing DOPC are attributed to the greater mis-match in lipid alkyl chains between DOPC and DPPC, than for POPC and DPPC. QENS studies, over the temperature range 283–323K, showed that the resulting data were best modelled by two Lorentzian functions: a narrow component, describing the “in-plane” lipid diffusion, and a broader component, describing the lipid alkyl chain segmental relaxation. The overall “in-plane” diffusion was found to show a significant reduction upon increasing temperature due to the vesicle membranes transitioning from one containing rafts to one where the component lipids are homogeneously mixed. The use of different isotopic combinations allowed the measured overall reduction of in-plane diffusion to be understood in terms of an increase in diffusion of the saturated DPPC lipid and a corresponding decrease in diffusion of the unsaturated DOPC/POPC lipid. As the rafts are considered to be composed principally of saturated lipid and cholesterol, the breakdown of rafts decreases the exposure of the DPPC to cholesterol whilst increasing the exposure of cholesterol to unsaturated lipid. These results show the sensitivity of lipid diffusion to local cholesterol concentration, and the importance of considering the local, rather that the global composition of a membrane when understanding the diffusion processes of lipids within the membrane. The novel combination of SANS and QENS allows a non-intrusive approach to characterize the structure and dynamics occurring in phase-separated model membranes which are designed to mimic the lateral heterogeneity of lipids seen in cellular membranes–a heterogeneity that can have pathological consequences.
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| 15. |
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| 16. |
- Binder, Eva, 1990-, et al.
(författare)
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Temperature-dependent creep of mature cement paste
- 2021
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Ingår i: ERICA CASH II Final Conference, January 25-27, 2021. - Vienna.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Mature cement pastes are subjected to isothermal, three-minute creep test under uniaxial compression at 20°C, 30°C, and 45°C. The macroscopic experiments are evaluated in the framework of linear viscoelasticity, based on a power-law creep function, considering that spontaneous elastic and time-dependent creep deformations are developing during the short loading phase. The modulus of elasticity is found to decrease slightly, and the creep modulus to decrease significantly with increasing temperature. These macroscopic findings are downscaled, in the field of continuum micromechanics, to microscopic hydrate-gel needles, based on a multiscale model. This allows for quantification of the activation energy of creep of the hydrate-gel, which is close to the activation energy of water.
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| 17. |
- Correa, Yubexi, et al.
(författare)
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High-Density Lipoprotein function is modulated by the SARS-CoV-2 spike protein in a lipid-type dependent manner
- 2023
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 645, s. 627-638
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Tidskriftsartikel (refereegranskat)abstract
- There is a close relationship between the SARS-CoV-2 virus and lipoproteins, in particular high-density lipoprotein (HDL). The severity of the coronavirus disease 2019 (COVID-19) is inversely correlated with HDL plasma levels. It is known that the SARS-CoV-2 spike (S) protein binds the HDL particle, probably depleting it of lipids and altering HDL function. Based on neutron reflectometry (NR) and the ability of HDL to efflux cholesterol from macrophages, we confirm these observations and further identify the preference of the S protein for specific lipids and the consequent effects on HDL function on lipid exchange ability. Moreover, the effect of the S protein on HDL function differs depending on the individuals lipid serum profile. Contrasting trends were observed for individuals presenting low triglycerides/high cholesterol serum levels (LTHC) compared to high triglycerides/high cholesterol (HTHC) or low triglycerides/low cholesterol serum levels (LTLC). Collectively, these results suggest that the S protein interacts with the HDL particle and, depending on the lipid profile of the infected individual, it impairs its function during COVID-19 infection, causing an imbalance in lipid metabolism.
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| 18. |
- Fischer, Katrin, et al.
(författare)
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The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- During beta -adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1 alpha. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1 alpha promoter. P62(Delta 69-251) mice show reduced expression of Ucp1 and Pgc-1 alpha with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1 alpha expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62(Delta 69-251) mice, global p62(-/-) and Ucp1-Cre p62(flx/flx) mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding. Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1 alpha. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1 alpha induction.
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| 19. |
- Geist, Juergen, et al.
(författare)
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Captive breeding of European freshwater mussels as a conservation tool : A review
- 2023
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Ingår i: Aquatic conservation. - : John Wiley & Sons. - 1052-7613 .- 1099-0755. ; 33:11, s. 1321-1359
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Tidskriftsartikel (refereegranskat)abstract
- Freshwater mussels are declining throughout their range. Their important ecological functions along with insufficient levels of natural recruitment have prompted captive breeding for population augmentation and questions about the usefulness and applicability of such measures. This article reviews the current state of captive breeding and rearing programmes for freshwater mussels in Europe. It considers the various species, strategies, and techniques of propagation, as well as the different levels of effort required according to rearing method, highlighting the key factors of success. Within the last 30 years, 46 breeding activities in 16 European countries have been reported, mainly of Margaritifera margaritifera and Unio crassus. Some facilities propagate species that are in a very critical situation, such as Pseudunio auricularius, Unio mancus, and Unio ravoisieri, or multiple species concurrently. In some streams, the number of released captive-bred mussels already exceeds the size of the remaining natural population. Rearing efforts range from highly intensive laboratory incubation to lower intensity methods using in-river mussel cages or silos. Most breeding efforts are funded by national and EU LIFE(+) grants, are well documented, and consider the genetic integrity of the propagated mussels. Limited long-term funding perspectives, the availability of experienced staff, water quality, and feeding/survival during early life stages are seen as the most important challenges. Successful captive breeding programmes need to be combined with restoration of the habitats into which the mussels are released. This work will benefit from an evidence-based approach, knowledge exchange among facilities, and an overall breeding strategy comprising multiple countries and conservation units.
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| 20. |
- Pichler, M. J., et al.
(författare)
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Butyrate producing colonic Clostridiales metabolise human milk oligosaccharides and cross feed on mucin via conserved pathways
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The early life human gut microbiota exerts life-long health effects on the host, but the mechanisms underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune- and metabolic disorders is enigmatic. Here, we describe catabolic pathways that support the growth of Roseburia and Eubacterium members on distinct human milk oligosaccharides (HMOs). The HMO pathways, which include enzymes with a previously unknown structural fold and specificity, were upregulated together with additional glycan-utilization loci during growth on selected HMOs and in co-cultures with Akkermansia muciniphila on mucin, suggesting an additional role in enabling cross-feeding and access to mucin O-glycans. Analyses of 4599 Roseburia genomes underscored the preponderance and diversity of the HMO utilization loci within the genus. The catabolism of HMOs by butyrate-producing Clostridiales may contribute to the competitiveness of this group during the weaning-triggered maturation of the microbiota. The assembly and maturation of the early life microbiome has life-long effects on human health. Here, the authors combine omics, functional assays and structural analyses to characterize the catabolic pathways that support the growth of butyrate producing Clostridiales members from the Roseburia and Eubacterium, on distinct human milk oligosaccharides.
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| 21. |
- Prasuhn, Jannik, et al.
(författare)
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Task matters-challenging the motor system allows distinguishing unaffected Parkin mutation carriers from mutation-free controls
- 2021
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 86, s. 101-104
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heterozygous carriers of Parkin mutations are suggested to be at risk of developing Parkinson's disease, while biallelic variants are associated with typical autosomal recessive early-onset PD. Investigating unaffected heterozygous mutation carriers holds the potential of a deeper understanding of monogenic PD and has implications for PD in general, in particular regarding the prodromal phase.Objectives: To discriminate healthy Parkin mutation carriers from healthy non-mutation carriers using a multimodal approach.Methods: Twenty-seven healthy heterozygous Parkin mutation carriers (13 female. age: 48 +/- 13 years) and 24 healthy non-mutation carriers (14 female. age: 48 +/- 15 years) from the CHRIS study (Cooperative Health Research in South Tyrol) were recalled based on their genetic profile and underwent a blinded assessment of motor and non-motor PD symptoms, transcranial sonography and sensor-based posturography and gait analyses under different conditions with increasing difficulty. For the latter, gradient-boosted trees were used to discriminate between carriers and non-carriers. The classification accuracy and the area under the curve of the receiver-operator characteristics curve were calculated.Results: We observed no differences concerning motor or non-motor symptoms and substantia nigra hyperechogenicity. The best gradient-boosted trees-based model on posturography measurements (tandem feet, eyes closed, firm surface), however, showed a classification accuracy of up to 86%. The best-performing gradientboosted trees-based model for gait analyses showed a balanced accuracy of up to 87% (dual-tasking).Conclusions: Sensor-based quantification of movements allows to discriminate unaffected heterozygous mutation carriers from mutation-free controls. Thereby, it is crucial to challenge the motor system with more difficult tasks to unmask subtle motor alterations.
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| 22. |
- Stelzer, C. P., et al.
(författare)
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Comparative analysis reveals within-population genome size variation in a rotifer is driven by large genomic elements with highly abundant satellite DNA repeat elements
- 2021
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Ingår i: BMC Biology. - : BioMed Central (BMC). - 1741-7007. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Eukaryotic genomes are known to display an enormous variation in size, but the evolutionary causes of this phenomenon are still poorly understood. To obtain mechanistic insights into such variation, previous studies have often employed comparative genomics approaches involving closely related species or geographically isolated populations within a species. Genome comparisons among individuals of the same population remained so far understudied-despite their great potential in providing a microevolutionary perspective to genome size evolution. The rotifer Brachionus asplanchnoidis represents one of the most extreme cases of within-population genome size variation among eukaryotes, displaying almost twofold variation within a geographic population.Results: Here, we used a whole-genome sequencing approach to identify the underlying DNA sequence differences by assembling a high-quality reference genome draft for one individual of the population and aligning short reads of 15 individuals from the same geographic population including the reference individual. We identified several large, contiguous copy number variable regions (CNVs), up to megabases in size, which exhibited striking coverage differences among individuals, and whose coverage overall scaled with genome size. CNVs were of remarkably low complexity, being mainly composed of tandemly repeated satellite DNA with only a few interspersed genes or other sequences, and were characterized by a significantly elevated GC-content. CNV patterns in offspring of two parents with divergent genome size and CNV patterns in several individuals from an inbred line differing in genome size demonstrated inheritance and accumulation of CNVs across generations.Conclusions: By identifying the exact genomic elements that cause within-population genome size variation, our study paves the way for studying genome size evolution in contemporary populations rather than inferring patterns and processes a posteriori from species comparisons.
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| 23. |
- Waldie, Sarah, et al.
(författare)
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ApoE and ApoE Nascent-Like HDL Particles at Model Cellular Membranes : Effect of Protein Isoform and Membrane Composition
- 2021
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Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (ApoE), an important mediator of lipid transportation in plasma and the nervous system, plays a large role in diseases such as atherosclerosis and Alzheimer's. The major allele variants ApoE3 and ApoE4 differ only by one amino acid. However, this difference has major consequences for the physiological behaviour of each variant. In this paper, we follow (i) the initial interaction of lipid-free ApoE variants with model membranes as a function of lipid saturation, (ii) the formation of reconstituted High-Density Lipoprotein-like particles (rHDL) and their structural characterisation, and (iii) the rHDL ability to exchange lipids with model membranes made of saturated lipids in the presence and absence of cholesterol [1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) with and without 20 mol% cholesterol]. Our neutron reflection results demonstrate that the protein variants interact differently with the model membranes, adopting different protein conformations. Moreover, the ApoE3 structure at the model membrane is sensitive to the level of lipid unsaturation. Small-angle neutron scattering shows that the ApoE containing lipid particles form elliptical disc-like structures, similar in shape but larger than nascent or discoidal HDL based on Apolipoprotein A1 (ApoA1). Neutron reflection shows that ApoE-rHDL do not remove cholesterol but rather exchange saturated lipids, as occurs in the brain. In contrast, ApoA1-containing particles remove and exchange lipids to a greater extent as occurs elsewhere in the body.
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| 24. |
- Zhang, Jiao-Long, et al.
(författare)
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Assessment of the Added Value of Multiscale Modeling of Concrete for Structural Analysis of Segmental Tunnel Rings
- 2021
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Ingår i: Encyclopedia of Materials. - : Elsevier. - 9780128197318 - 9780128197240 ; , s. 69-78
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Bokkapitel (refereegranskat)abstract
- This contribution deals with an assessment of the added value resulting from the use of a multiscale model of concrete as the basis for structural analysis of a segmental tunnel ring. The assessment rests on the comparison of a triad of results. They are obtained from a real-scale test of a segmental tunnel ring, from conventional structural analysis based on the concrete model of the fib Model Code, and from multiscale structural analysis based on a more recently developed multiscale model of concrete. In the experiment, a segmental tunnel ring was subjected to point loads simulating ground pressure. For both modes of structural analysis, a nonlinear hybrid method was used. It is termed hybrid, because not only the external loading was part of the input, but also the displacements at the joints were measured during testing. The method is nonlinear, because bending-induced cracking of concrete is accounted for. The analyzed segmental tunnel ring was subdivided into elements that are either intact or contain one central crack band. Structural analysis was based on transfer relations, representing analytical solutions of the linear theory of circular arches. As for the convergences, it is shown that conventional and multiscale structural analysis are equally reliable. Concerning cracking of concrete, it is demonstrated that multiscale structural analysis allows for a correct prediction of the initiation of cracking, while the results from conventional structural analysis overestimate the external loading at initiation of cracking by 86%. This underlines the added value of multiscale structural analysis for durability analysis of segmental tunnel linings with a designed service life of 100 years and more. © 2021 Elsevier Ltd. All rights reserved.
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| 25. |
- Zhang, Jiaolong, et al.
(författare)
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On the added value of multi-scale modeling of concrete
- 2022
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Ingår i: Frontiers of Structural and Civil Engineering. - : Springer. - 2095-2430 .- 2095-2449. ; 16:1, s. 1-23
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Tidskriftsartikel (refereegranskat)abstract
- This review of the added value of multi-scale modeling of concrete is based on three representative examples. The first one is concerned with the analysis of experimental data, taken from four high-dynamic tests. The structural nature of the high-dynamic strength increase can be explained by using a multi-scale model. It accounts for the microstructure of the specimens. The second example refers to multi-scale thermoelastic analysis of concrete pavements, subjected to solar heating. A sensitivity analysis with respect to the internal relative humidity (RH) of concrete has underlined the great importance of the RH for an assessment of the risk of microcracking of concrete. The third example deals with multi-scale structural analysis of a real-scale test of a segmental tunnel ring. It has turned out that multi-scale modeling of concrete enables more reliable predictions of crack opening displacements in tunnel segments than macroscopic models taken from codes of practice. Overall, it is concluded that multi-scale models have indeed a significant added value. However, its degree varies with these examples. In any case, it can be assessed by means of a comparison of the results from three sources, namely, multi-scale structural analysis, conventional structural analysis, and experiments.
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