| 1. |
- Andersson, A. F., et al.
(författare)
-
Comparative analysis of human gut microbiota by barcoded pyrosequencing
- 2008
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:7
-
Tidskriftsartikel (refereegranskat)abstract
- Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.
|
|
| 2. |
- Andersson, Magnus, et al.
(författare)
-
A proposed time-resolved X-ray scattering approach to track local and global conformational changes in membrane transport proteins
- 2008
-
Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 16:1, s. 21-28
-
Tidskriftsartikel (refereegranskat)abstract
- Time-resolved X-ray scattering has emerged as a powerful technique for studying the rapid structural dynamics of small molecules in solution. Membrane-protein-catalyzed transport processes frequently couple large-scale conformational changes of the transporter with local structural changes perturbing the uptake and release of the transported substrate. Using light-driven halide ion transport catalyzed by halorhodopsin as a model system, we combine molecular dynamics simulations with X-ray scattering calculations to demonstrate how small-molecule time-resolved X-ray scattering can be extended to the study of membrane transport processes. In particular, by introducing strongly scattering atoms to label specific positions within the protein and substrate, the technique of time-resolved wide-angle X-ray scattering can reveal both local and global conformational changes. This approach simultaneously enables the direct visualization of global rearrangements and substrate movement, crucial concepts that underpin the alternating access paradigm for membrane transport proteins.
|
|
| 3. |
- Bergström, Sofia, et al.
(författare)
-
Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease
- 2021
-
Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:7, s. 1456-1470
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Decreased amyloid beta (A beta) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of A beta 42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.
|
|
| 4. |
- Bjursell, Magnus K., et al.
(författare)
-
Adenosine Kinase Deficiency Disrupts the Methionine Cycle and Causes Hypermethioninemia, Encephalopathy, and Abnormal Liver Function
- 2011
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 89:4, s. 507-515
-
Tidskriftsartikel (refereegranskat)abstract
- Four inborn errors of metabolism (IEMs) are known to cause hypermethioninemia by directly interfering with the methionine cycle. Hypermethioninemia is occasionally discovered incidentally, but it is often disregarded as an unspecific finding, particularly if liver disease is involved. In many individuals the hypermethioninemia resolves without further deterioration, but it can also represent an early sign of a severe, progressive neurodevelopmental disorder. Further investigation of unclear hypermethioninemia is therefore important. We studied two siblings affected by severe developmental delay and liver dysfunction. Biochemical analysis revealed increased plasma levels of methionine, S-adenosylmethionine (Ado Met), and S-adenosylhomocysteine (AdoHcy) but normal or mildly elevated homocysteine (Hcy) levels, indicating a block in the methionine cycle. We excluded S-adenosylhomocysteine hydrolase (SAHH) deficiency, which causes a similar biochemical phenotype, by using genetic and biochemical techniques and hypothesized that there was a functional block in the SAHH enzyme as a result of a recessive mutation in a different gene. Using exome sequencing, we identified a homozygous c.902C>A (p.Ala301Glu) missense mutation in the adenosine kinase gene (ADK), the function of which fits perfectly with this hypothesis. Increased urinary adenosine excretion confirmed ADK deficiency in the siblings. Four additional individuals from two unrelated families with a similar presentation were identified and shown to have a homozygous c.653A>C (p.Asp218Ala) and c.38G>A (p.Gly13Glu) mutation, respectively, in the same gene. All three missense mutations were deleterious, as shown by activity measurements on recombinant enzymes. ADK deficiency is a previously undescribed, severe IEM shedding light on a functional link between the methionine cycle and adenosine metabolism.
|
|
| 5. |
- Björk, Mats, 1960-, et al.
(författare)
-
Methane emissions from macrophyte beach wrack on Baltic seashores
- 2023
-
Ingår i: Ambio. - : Springer Nature. - 0044-7447 .- 1654-7209. ; 52:1, s. 171-181
-
Tidskriftsartikel (refereegranskat)abstract
- Beach wrack of marine macrophytes is a natural component of many beaches. To test if such wrack emits the potent greenhouse gas methane, field measurements were made at different seasons on beach wrack depositions of different ages, exposure, and distance from the water. Methane emissions varied greatly, from 0 to 176 mg CH4-C m−2 day−1, with a clear positive correlation between emission and temperature. Dry wrack had lower emissions than wet. Using temperature data from 2016 to 2020, seasonal changes in fluxes were calculated for a natural wrack accumulation area. Such calculated average emissions were close to zero during winter, but peaked in summer, with very high emissions when daily temperatures exceeded 20 °C. We conclude that waterlogged beach wrack significantly contributes to greenhouse gas emissions and that emissions might drastically increase with increasing global temperatures. When beach wrack is collected into heaps away from the water, the emissions are however close to zero.
|
|
| 6. |
- Björnson, Elias, 1988, et al.
(författare)
-
Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization
- 2015
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 13:9, s. 2014-2026
-
Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) is a deadly form of liver cancer that is increasingly prevalent. We analyzed global gene expression profiling of 361 HCC tumors and 49 adjacent noncancerous liver samples by means of combinatorial network-based analysis. We investigated the correlation between transcriptome and proteome of HCC and reconstructed a functional genome-scale metabolic model (GEM) for HCC. We identified fundamental metabolic processes required for cell proliferation using the network centric view provided by the GEM. Our analysis revealed tight regulation of fatty acid biosynthesis (FAB) and highly significant deregulation of fatty acid oxidation in HCC. We predicted mitochondrial acetate as an emerging substrate for FAB through upregulation of mitochondrial acetyl-CoA synthetase (ACSS1) in HCC. We analyzed heterogeneous expression of ACSS1 and ACSS2 between HCC patients stratified by high and low ACSS1 and ACSS2 expression and revealed that ACSS1 is associated with tumor growth and malignancy under hypoxic conditions in human HCC.
|
|
| 7. |
- Burgos-Parra, E., et al.
(författare)
-
Investigation of magnetic droplet solitons using x-ray holography with extended references
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- A dissipative magnetic soliton, or magnetic droplet, is a structure that has been predicted to exist within a thin magnetic layer when non-linearity is balanced by dispersion, and a driving force counteracts the inherent damping of the spin precession. Such a soliton can be formed beneath a nano-contact (NC) that delivers a large spin-polarized current density into a magnetic layer with perpendicular magnetic anisotropy. Although the existence of droplets has been confirmed from electrical measurements and by micromagnetic simulations, only a few attempts have been made to directly observe the magnetic landscape that sustains these structures, and then only for a restricted set of experimental parameter values. In this work we use and x-ray holography technique HERALDO, to image the magnetic structure of the [ Co/ Ni] x4 multilayer within a NC orthogonal pseudo spin-valve, for different range of magnetic fields and injected electric currents. The magnetic configuration imaged at -33 mA and 0.3 T for devices with 90 nm NC diameter reveals a structure that is within the range of current where the droplet soliton exist based on our electrical measurements and have it is consistent with the expected size of the droplet (similar to 100 nm diameter) and its spatial position within the sample. We also report the magnetisation configurations observed at lower DC currents in the presence of fields (0-50 mT), where it is expected to observe regimes of the unstable droplet formation.
|
|
| 8. |
- Chen, Yun, 1966, et al.
(författare)
-
Characterization of VCAM-1-Binding Peptide-Functionalized Quantum Dots for Molecular Imaging of Inflamed Endothelium
- 2013
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammation-induced activation of endothelium constitutes one of the earliest changes during atherogenesis. New imaging techniques that allow detecting activated endothelial cells can improve the identification of persons at high cardiovascular risk in early stages. Quantum dots (QDs) have attractive optical properties such as bright fluorescence and high photostability, and have been increasingly studied and developed for bio-imaging and bio-targeting applications. We report here the development of vascular cell adhesion molecule-1 binding peptide (VCAM-1 binding peptide) functionalized QDs (VQDs) from amino QDs. It was found that the QD fluorescence signal in tumor necrosis factor alpha (TNF-alpha) treated endothelial cells in vitro was significantly higher when these cells were labeled with VQDs than amino QDs. The VQD labeling of TNF-alpha-treated endothelial cells was VCAM-1 specific since pre-incubation with recombinant VCAM-1 blocked cells' uptake of VQDs. Our ex vivo and in vivo experiments showed that in the inflamed endothelium, QD fluorescence signal from VQDs was also much stronger than that of amino QDs. Moreover, we observed that the QD fluorescence peak was significantly blue-shifted after VQDs interacted with aortic endothelial cells in vivo and in vitro. A similar blue-shift was observed after VQDs were incubated with recombinant VCAM-1 in tube. We anticipate that the specific interaction between VQDs and VCAM-1 and the blue-shift of the QD fluorescence peak can be very useful for VCAM-1 detection in vivo.
|
|
| 9. |
- Chung, Sunjae, et al.
(författare)
-
Direct Observation of Zhang-Li Torque Expansion of Magnetic Droplet Solitons
- 2018
-
Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 120:21
-
Tidskriftsartikel (refereegranskat)abstract
- Magnetic droplets are nontopological dynamical soli tons that can be nucleated in nanocontact based spin torque nano-oscillators (STNOs) with perpendicular magnetic anisotropy free layers. While theory predicts that the droplet should be of the same size as the nanocontact, its inherent drift instability has thwarted attempts at observing it directly using microscopy techniques. Here, we demonstrate highly stable magnetic droplets in all-perpendicular STNOs and present the first detailed droplet images using scanning transmission X-ray microscopy. In contrast to theoretical predictions, we find that the droplet diameter is about twice as large as the nanocontact. By extending the original droplet theory to properly account for the lateral current spread underneath the nanocontact, we show that the large discrepancy primarily arises from current-in-plane Zhang-Li torque adding an outward pressure on the droplet perimeter. Electrical measurements on droplets nucleated using a reversed current in the antiparallel state corroborate this picture.
|
|
| 10. |
- Chung, Sunjae, et al.
(författare)
-
Spin transfer torque generated magnetic droplet solitons (invited)
- 2014
-
Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 115:17
-
Tidskriftsartikel (refereegranskat)abstract
- We present recent experimental and numerical advancements in the understanding of spin transfer torque generated magnetic droplet solitons. The experimental work focuses on nano-contact spin torque oscillators (NC-STOs) based on orthogonal (pseudo) spin valves where the Co fixed layer has an easy-plane anisotropy, and the [Co/Ni] free layer has a strong perpendicular magnetic anisotropy. The NC-STO resistance and microwave signal generation are measured simultaneously as a function of drive current and applied perpendicular magnetic field. Both exhibit dramatic transitions at a certain current dependent critical field value, where the microwave frequency drops 10 GHz, modulation sidebands appear, and the resistance exhibits a jump, while the magnetoresistance changes sign. We interpret these observations as the nucleation of a magnetic droplet soliton with a large fraction of its magnetization processing with an angle greater than 90 degrees, i.e., around a direction opposite that of the applied field. This interpretation is corroborated by numerical simulations. When the field is further increased, we find that the droplet eventually collapses under the pressure from the Zeeman energy. (C) 2014 AIP Publishing LLC.
|
|
