| 1. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 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
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 2. |
- Adiels, Martin, 1976, et al.
(författare)
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Kinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans.
- 2015
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 6:NOV, s. 342-
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Forskningsöversikt (refereegranskat)abstract
- To develop novel strategies for prevention and treatment of dyslipidemia, it is essential to understand the pathophysiology of dyslipoproteinemia in humans. Lipoprotein metabolism is a complex system in which abnormal concentrations of various lipoprotein particles can result from alterations in their rates of production, conversion, and/or catabolism. Traditional methods that measure plasma lipoprotein concentrations only provide static estimates of lipoprotein metabolism and hence limited mechanistic information. By contrast, the use of tracers labeled with stable isotopes and mathematical modeling, provides us with a powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering our understanding of the pathogenesis of dyslipoproteinemia.
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| 3. |
- Adler, Jeremy, et al.
(författare)
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Membrane topography and the overestimation of protein clustering in single molecule localisation microscopy - identification and correction
- 2024
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- According to single-molecule localisation microscopy almost all plasma membrane proteins are clustered. We demonstrate that clusters can arise from variations in membrane topography where the local density of a randomly distributed membrane molecule to a degree matches the variations in the local amount of membrane. Further, we demonstrate that this false clustering can be differentiated from genuine clustering by using a membrane marker to report on local variations in the amount of membrane. In dual colour live cell single molecule localisation microscopy using the membrane probe DiI alongside either the transferrin receptor or the GPI-anchored protein CD59, we found that pair correlation analysis reported both proteins and DiI as being clustered, as did its derivative pair correlation-photoactivation localisation microscopy and nearest neighbour analyses. After converting the localisations into images and using the DiI image to factor out topography variations, no CD59 clusters were visible, suggesting that the clustering reported by the other methods is an artefact. However, the TfR clusters persisted after topography variations were factored out. We demonstrate that membrane topography variations can make membrane molecules appear clustered and present a straightforward remedy suitable as the first step in the cluster analysis pipeline. Variations in membrane topography can lead to the overestimation of protein clustering which can be avoided using a second image of a membrane marker, demonstrated with simulations and live cell SMLM.
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| 4. |
- Ahlberg, Martina, et al.
(författare)
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Freezing and thawing magnetic droplet solitons
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic droplets are a type of non-topological magnetic soliton, which are stabilised and sustained by spin-transfer torques for instance. Without this, they would collapse. Here Ahlberg et al show that by decreasing the applied magnetic field, droplets can be frozen, forming a static nanobubble Magnetic droplets are non-topological magnetodynamical solitons displaying a wide range of complex dynamic phenomena with potential for microwave signal generation. Bubbles, on the other hand, are internally static cylindrical magnetic domains, stabilized by external fields and magnetostatic interactions. In its original theory, the droplet was described as an imminently collapsing bubble stabilized by spin transfer torque and, in its zero-frequency limit, as equivalent to a bubble. Without nanoscale lateral confinement, pinning, or an external applied field, such a nanobubble is unstable, and should collapse. Here, we show that we can freeze dynamic droplets into static nanobubbles by decreasing the magnetic field. While the bubble has virtually the same resistance as the droplet, all signs of low-frequency microwave noise disappear. The transition is fully reversible and the bubble can be thawed back into a droplet if the magnetic field is increased under current. Whereas the droplet collapses without a sustaining current, the bubble is highly stable and remains intact for days without external drive. Electrical measurements are complemented by direct observation using scanning transmission x-ray microscopy, which corroborates the analysis and confirms that the bubble is stabilized by pinning.
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| 5. |
- Ahlquist, Mårten, et al.
(författare)
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Dispersion and Back-Donation Gives Tetracoordinate [Pd(PPh3)4]
- 2011
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 50:49, s. 11794-11797
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Tidskriftsartikel (refereegranskat)abstract
- 18e R.I.P. The apparent compliance of [Pd(PPh3)4] ("tetrakis") with the 18-electron rule is not due to an electronic preference on the central metal. Pd is valence-saturated already by two ligands. Further ligand addition gives a minor energy gain, and is only possible due to strong back-bonding. Dispersion corrections are needed for properly describing the interactions between the ligands.
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| 6. |
- Ahlquist, Mårten, et al.
(författare)
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Oxidative addition of aryl chlorides to monoligated palladium(0): A DFT-SCRF study
- 2007
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Ingår i: Organometallics. - : American Chemical Society (ACS). - 0276-7333 .- 1520-6041. ; 26:3, s. 550-553
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative addition of aryl chlorides to palladium has been investigated by hybrid density functional theory methods (B3LYP), including a continuum model describing the solvent implicitly. A series of para-substituted aryl chlorides were studied to see the influence of electronic effects on the reaction. It was found that the experimentally observed higher reactivity of the more electron deficient aryl chlorides is due to their ability to accept back-donation from Pd-0 and form reasonably strong pre-reactive complexes. This effect is less pronounced in the transition state; when it is measured from the pre-reactive complex, the barrier to oxidative addition is actually higher for the electron-deficient aryl chlorides, but the overall reaction barrier is still lower than for the electron-rich aryl chlorides.
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| 7. |
- Ahmadi, K., et al.
(författare)
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Inducing Dzyaloshinskii-Moriya interaction in symmetrical multilayers using post annealing
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The interfacial Dzyaloshinskii-Moriya Interaction (iDMI) is an antisymmetric exchange interaction that is induced by the broken inversion symmetry at the interface of, e.g., a ferromagnet/heavy metal. Thus, the presence of iDMI is not expected in symmetrical multilayer stacks of such structures. Here, we use thermal annealing to induce the iDMI in a [Py/Pt](x10) symmetrical multilayer stack. Brillouin light scattering spectroscopy is used to directly evidence the iDMI induction in the annealed sample. Structural characterizations highlight the modified crystallinity as well as a higher surface roughness of the sample after annealing. First principles electronic structure calculations demonstrate a monotonic increase of the iDMI with the interfacial disorder due to the interdiffusion of atoms, depicting the possible origin of the induced iDMI. The presented method can be used to tune the iDMI strength in symmetric multilayers, which are the integral part of racetrack memories, magnonic devices as well as spin-orbitronic elements.
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| 8. |
- Ahmed, M., et al.
(författare)
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Human serum albumin-based probes for molecular targeting of macrophage scavenger receptors
- 2019
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Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 14, s. 3723-3741
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammation and accumulation of macrophages are key features of unstable atherosclerotic plaques. The ability of macrophages to take up molecular probes can be exploited in new clinical imaging methods for the detection of unstable atherosclerotic lesions. We investigated whether modifications of human serum albumin (HSA) could be used to target macrophages efficiently in vitro. Materials and methods: Maleylated and aconitylated HSA were compared with unmodified HSA. Fluorescent or radiolabeled (89 Zr) modified HSA was used in in vitro experiments to study cellular uptake by differentiated THP-1 cells and primary human macrophages. The time course of uptake was evaluated by flow cytometry, confocal microscopy, real-time microscopy and radioactivity measurements. The involvement of scavenger receptors (SR-A1, SR-B2, LOX-1) was assessed by knockdown experiments using RNA interference, by blocking experiments and by assays of competition by modified low-density lipoprotein. Results: Modified HSA was readily taken up by different macrophages. Uptake was mediated nonexclusively via the scavenger receptor SR-A1 (encoded by the MSR1 gene). Knockdown of CD36 and ORL1 had no influence on the uptake. Modified HSA was preferentially taken up by human macrophages compared with other vascular cell types such as endothelial cells and smooth muscle cells. Conclusions: Modified89Zr-labeled HSA probes were recognized by different subsets of polarized macrophages, and maleylated HSA may be a promising radiotracer for radio-nuclide imaging of macrophage-rich inflammatory vascular diseases. © 2019 Ahmed et al.
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| 9. |
- Ahmed, M., et al.
(författare)
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Molecular Imaging of a New Multimodal Microbubble for Adhesion Molecule Targeting
- 2019
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Ingår i: Cellular and Molecular Bioengineering. - : Springer Science and Business Media LLC. - 1865-5025 .- 1865-5033. ; 12:1, s. 15-32
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionInflammation is an important risk-associated component of many diseases and can be diagnosed by molecular imaging of specific molecules. The aim of this study was to evaluate the possibility of targeting adhesion molecules on inflammation-activated endothelial cells and macrophages using an innovative multimodal polyvinyl alcohol-based microbubble (MB) contrast agent developed for diagnostic use in ultrasound, magnetic resonance, and nuclear imaging.MethodsWe assessed the binding efficiency of antibody-conjugated multimodal contrast to inflamed murine or human endothelial cells (ECs), and to peritoneal macrophages isolated from rats with peritonitis, utilizing the fluorescence characteristics of the MBs. Single-photon emission tomography (SPECT) was used to illustrate Tc-99m-labeled MB targeting and distribution in an experimental in vivo model of inflammation.ResultsFlow cytometry and confocal microscopy showed that binding of antibody-targeted MBs to the adhesion molecules ICAM-1, VCAM-1, or E-selectin, expressed on cytokine-stimulated ECs, was up to sixfold higher for human and 12-fold higher for mouse ECs, compared with that of non-targeted MBs. Under flow conditions, both VCAM-1- and E-selectin-targeted MBs adhered more firmly to stimulated human ECs than to untreated cells, while VCAM-1-targeted MBs adhered best to stimulated murine ECs. SPECT imaging showed an approximate doubling of signal intensity from the abdomen of rats with peritonitis, compared with healthy controls, after injection of anti-ICAM-1-MBs.ConclusionsThis novel multilayer contrast agent can specifically target adhesion molecules expressed as a result of inflammatory stimuli in vitro, and has potential for use in disease-specific multimodal diagnostics in vivo using antibodies against targets of interest.
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| 10. |
- Al-Khalili, A, et al.
(författare)
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Dissociative recombination cross section and branching ratios of protonated dimethyl disulfide and N-methylacetamide
- 2004
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 121:12, s. 5700-5708
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Tidskriftsartikel (refereegranskat)abstract
- Dimethyl disulfide (DMDS) and N-methylacetamide are two first choice model systems that represent the disulfide bridge bonding and the peptide bonding in proteins. These molecules are therefore suitable for investigation of the mechanisms involved when proteins fragment under electron capture dissociation (ECD). The dissociative recombination cross sections for both protonated DMDS and protonated N-methylacetamide were determined at electron energies ranging from 0.001 to 0.3 eV. Also, the branching ratios at 0 eV center-of-mass collision energy were determined. The present results give support for the indirect mechanism of ECD, where free hydrogen atoms produced in the initial fragmentation step induce further decomposition. We suggest that both indirect and direct dissociations play a role in ECD.
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