| 1. |
- Sarwar, Nadeem, et al.
(författare)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
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Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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| 2. |
- Svahn, Sara L, et al.
(författare)
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Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis
- 2016
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Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 84:4, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics, S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus. Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.
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| 3. |
- Zendejas Medina, León, et al.
(författare)
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Enhancing corrosion resistance, hardness, and crack resistance in magnetron sputtered high entropy CoCrFeMnNi coatings by adding carbon
- 2021
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Ingår i: Materials & design. - : Elsevier BV. - 0264-1275 .- 1873-4197. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- This study explores carbon addition as a materials design approach for simultaneously improving the hardness, crack resistance, and corrosion resistance of high entropy thin films. CoCrFeMnNi was selected as a starting point, due to its high concentration of weak carbide formers. The suppression of carbides is crucial to the approach, as carbide formation can decrease both ductility and corrosion resistance. Films with 0, 6, and 11 at.% C were deposited by magnetron co-sputtering, using a graphite target and a sintered compound target. The samples with 0 at.% C crystallized with a mixture of a cubic closed packed (ccp) phase and the intermetallic chi-phase. With 6 and 11 at.% C, the films were amorphous and homogenous down to the nm-scale. The hardness of the films increased from 8 GPa in the carbon-free film to 16 GPa in the film with 11 at.% C. Furthermore, the carbon significantly improved the crack resistance as shown in fragmentation tests, where the crack density was strongly reduced. The changes in mechanical properties were primarily attributed to the shift from crystalline to amorphous. Lastly, the carbon improved the corrosion resistance by a progressive lowering of the corrosion current and the passive current with increasing carbon concentration.
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| 4. |
- Zendejas Medina, León, 1993-, et al.
(författare)
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Magnetron sputtered high entropy alloy/amorphous carbon nanocomposite coatings
- 2023
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Ingår i: Materials Today Communications. - : Elsevier. - 2352-4928. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Magnetron sputter deposition of metal/carbon nanocomposites has been explored for many metals and a few alloys. In this paper, the formation of nanocomposites based on complex high entropy alloys (HEAs) was explored, focusing on the effect of the average carbon affinity on the phase formation. Two HEA systems were compared: CoCrFeMnNi and Cr26Fe27Ni27Ta20. For each alloy, around 20–50 at% carbon was added through combinatorial co-sputtering. Thermodynamic calculations predicted decomposition of these materials into multiple alloy phases, metal carbides, and, at higher concentrations, free graphitic carbon. Free carbon was found in the coatings at carbon concentrations above 28 and 33 at% for the CoCrFeMnNi and Cr26Fe27Ni27Ta20 systems, respectively, which agreed with the theoretical predictions. However, the segregation of metallic elements and the formation of crystalline carbides were suppressed by the rapid quenching during deposition. All coatings were, instead, amorphous and consisted of either a single metallic phase or a mixture of a metallic phase and sp2- and sp3-hybridized carbon. Mechanical and electrochemical tests were performed, including in-situ fragmentation tests to quantify the crack resistance. The presence of free carbon made the coatings softer than the corresponding single-phase materials. Under tensile strain, the nanocomposite coatings formed a larger number of narrower cracks and exhibited less delamination at high strains.
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| 5. |
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| 6. |
- Berggren, Martin, et al.
(författare)
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Quality transformation of dissolved organic carbon during water transit through lakes : contrasting controls by photochemical and biological processes
- 2018
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Ingår i: Biogeosciences. - : European Geosciences Union (EGU). - 1726-4170 .- 1726-4189. ; 15:2, s. 457-470
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Tidskriftsartikel (refereegranskat)abstract
- Dissolved organic carbon (DOC) may be removed, transformed, or added during water transit through lakes, resulting in changes in DOC composition and pigmentation (color). However, the process-based understanding of these changes is incomplete, especially for headwater lakes. We hypothesized that because heterotrophic bacteria preferentially consume noncolored DOC, while photochemical processing removes colored fractions, the overall changes in DOC color upon water passage through a lake depend on the relative importance of these two processes, accordingly. To test this hypothesis we combined laboratory experiments with field studies in nine boreal lakes, assessing both the relative importance of different DOC decay processes (biological or photochemical) and the loss of color during water transit time (WTT) through the lakes. We found that influence from photo-decay dominated changes in DOC quality in the epilimnia of relatively clear headwater lakes, resulting in systematic and selective net losses of colored DOC. However, in highly pigmented brown-water lakes (absorbance at 420 nm > 7 m(-1)) biological processes dominated, and there was no systematic relationship between color loss and WTT. Moreover, in situ data and dark experiments supported our hypothesis on the selective microbial removal of nonpigmented DOC, mainly of low molecular weight, leading to persistent water color in these highly colored lakes. Our study shows that brown headwater lakes may not conform to the commonly reported pattern of the selective removal of colored constituents in freshwaters, as DOC can show a sustained degree of pigmentation upon transit through these lakes.
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| 7. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 8. |
- Brydegaard, Mikkel, et al.
(författare)
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Can the narrow red bands of dragonflies be used to perceive wing interference patterns?
- 2018
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 8:11, s. 5369-5384
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Tidskriftsartikel (refereegranskat)abstract
- Despite numerous studies of selection on position and number of spectral vision bands, explanations to the function of narrow spectral bands are lacking. We investigate dragonflies (Odonata), which have the narrowest spectral bands reported, in order to investigate what features these narrow spectral bands may be used to perceive. We address whether it is likely that narrow red bands can be used to identify conspecifics by the optical signature from wing interference patterns (WIPs). We investigate the optical signatures of Odonata wings using hyperspectral imaging, laser profiling, ellipsometry, polarimetric modulation spectroscopy, and laser radar experiments. Based on results, we estimate the prospects for Odonata perception of WIPs to identify conspecifics in the spectral, spatial, intensity, polarization, angular, and temporal domains. We find six lines of evidence consistent with an ability to perceive WIPs. First, the wing membrane thickness of the studied Odonata is 2.3 μm, coinciding with the maximal thickness perceivable by the reported bandwidth. Second, flat wings imply that WIPs persist from whole wings, which can be seen at a distance. Third, WIPs constitute a major brightness in the visual environment only second after the solar disk. Fourth, WIPs exhibit high degree of polarization and polarization vision coincides with frontal narrow red bands in Odonata. Fifth, the angular light incidence on the Odonata composite eye provides all prerequisites for direct assessment of the refractive index which is associated with age. Sixth, WIPs from conspecifics in flight make a significant contribution even to the fundamental wingbeat frequency within the flicker fusion bandwidth of Odonata vision. We conclude that it is likely that WIPs can be perceived by the narrow red bands found in some Odonata species and propose future behavioral and electrophysiological tests of this hypothesis.
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| 9. |
- Buggert, Marcus, et al.
(författare)
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CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
- 2016
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Ingår i: AIDS. - 0269-9370. ; 30:16, s. 2415-2426
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome. DESIGN:: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T cell subpopulations linked to infection type and disease stage. RESULTS:: HIV-2-infected individuals had early- and late-differentiated CD4+ T cell clusters with lower activation (CD38+HLA-DR+) and exhaustion (PD-1) than HIV-1 and HIV-D-infected subjects. We also noted that aviremic HIV-2-infected individuals possessed fewer CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegatives, aviremic HIV-2-infected subjects had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with suboptimal percentage of CD4+ T cells. CONCLUSIONS:: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of ART also to individuals with aviremic HIV-2 infection.
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| 10. |
- Buggert, Marcus, et al.
(författare)
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Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease
- 2018
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- CD4+ T cells subsets have a wide range of important helper and regulatory functions in the immune system. Several studies have specifically suggested that circulating effector CD4+ T cells may play a direct role in control of HIV replication through cytolytic activity or autocrine β-chemokine production. However, it remains unclear whether effector CD4+ T cells expressing cytolytic molecules and β-chemokines are present within lymph nodes (LNs), a major site of HIV replication. Here, we report that expression of β-chemokines and cytolytic molecules are enriched within a CD4+ T cell population with high levels of the T-box transcription factors T-bet and eomesodermin (Eomes). This effector population is predominately found in peripheral blood and is limited in LNs regardless of HIV infection or treatment status. As a result, CD4+ T cells generally lack effector functions in LNs, including cytolytic capacity and IFNγ and β-chemokine expression, even in HIV elite controllers and during acute/early HIV infection. While we do find the presence of degranulating CD4+ T cells in LNs, these cells do not bear functional or transcriptional effector T cell properties and are inherently poor to form stable immunological synapses compared to their peripheral blood counterparts. We demonstrate that CD4+ T cell cytolytic function, phenotype, and programming in the peripheral blood is dissociated from those characteristics found in lymphoid tissues. Together, these data challenge our current models based on blood and suggest spatially and temporally dissociated mechanisms of viral control in lymphoid tissues.
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