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Sökning: WFRF:(Hellgren Lars I.)

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1.
  • Mullins, N., et al. (författare)
  • Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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2.
  • Shin, J. H., et al. (författare)
  • IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
  • 2007
  • Ingår i: Genes Immun. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
  • Tidskriftsartikel (refereegranskat)abstract
    • In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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3.
  • Tjellström, Henrik, et al. (författare)
  • Lipid asymmetry in plant plasma membranes : phosphate deficiency-induced phospholipid replacement is restricted to the cytosolic leaflet
  • 2010
  • Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 24:4, s. 1128-1138
  • Tidskriftsartikel (refereegranskat)abstract
    • As in other eukaryotes, plant plasma membranes contain sphingolipids, phospholipids, and free sterols. In addition, plant plasma membranes also contain sterol derivatives and usually <5 mol% of a galactolipid, digalactosyldiacylglycerol (DGDG). We earlier reported that compared to fully fertilized oats (Avena sativa), oats cultivated without phosphate replaced up to 70 mol% of the root plasma membrane phospholipids with DGDG. Here, we investigated the implications of a high DGDG content on membrane properties. The phospholipid-to-DGDG replacement almost exclusively occurred in the cytosolic leaflet, where DGDG constituted up to one-third of the lipids. In the apoplastic (exoplasmic) leaflet, as well as in rafts, phospholipids were not replaced by DGDG, but by acylated sterol glycosides. Liposome studies revealed that the chain ordering in free sterol/phospholipid mixtures clearly decreased when > 5mol% DGDG was included. As both the apoplastic plasma membrane leaflet (probably the major water permeability barrier) and rafts both contain only trace amounts of DGDG, we conclude that this lipid class is not compatible with membrane functions requiring a high degree of lipid order. By not replacing phospholipids site specifically with DGDG, negative functional effects of this lipid in the plasma membrane are avoided.
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4.
  • Sedimbi, S. K., et al. (författare)
  • SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
  • 2007
  • Ingår i: Genes Immun. - : Nature Publishing Group. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
  • Tidskriftsartikel (refereegranskat)abstract
    • SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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5.
  • Bendsen, Nathalie T., et al. (författare)
  • Effect of industrially produced trans fat on markers of systemic inflammation : evidence from a randomized trial in women
  • 2011
  • Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 52:10, s. 1821-1828
  • Tidskriftsartikel (refereegranskat)abstract
    • Consumption of industrially produced trans fatty acids (IP-TFA) has been positively associated with systemic markers of low-grade inflammation and endothelial dysfunction in cross-sectional studies, but results from intervention studies are inconclusive. Therefore, we conducted a 16 week double-blind parallel intervention study with the objective to examine the effect of IP-TFA intake on bio-markers of inflammation, oxidative stress, and endothelial dysfunction. Fifty-two healthy overweight postmenopausal women (49 completers) were randomly assigned to receive either partially hydrogenated soybean oil (15.7 g/day IP-TFA) or control oil without IP-TFA. After 16 weeks, IP-TFA intake increased baseline-adjusted serum tumor necrosis factor (TNF) alpha by 12% [95% confidence interval (CI): 5-20; P = 0.002] more in the IP-TFA group compared with controls. Plasma soluble TNF receptors 1 and 2 were also increased by IP-TFA [155 pg/ml (CI: 63-247); P < 0.001 and 480 pg/ml (CI: 72-887); P = 0.02, respectively]. Serum C-reactive protein, interleukin (IL) 6 and adiponectin and subcutaneous abdominal adipose tissue mRNA expression of IL6, IL8, TNF alpha, and adiponectin as well as ceramide content were not affected by IP-TFA, nor was urinary 8-iso-prostaglandin-F(2 alpha). In conclusion, this dietary trial indicates that the mechanisms linking dietary IP-TFA to cardiovascular disease may involve activation of the TNF alpha system.
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6.
  • Broitman, E, et al. (författare)
  • Letter: Electrical properties of carbon nitride thin films : Role of morphology and hydrogen content
  • 2002
  • Ingår i: Journal of Electronic Materials. - 0361-5235 .- 1543-186X. ; 31:9, s. 957-961
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • The influence of hydrogen content and ambient humidity on the electrical properties of carbon nitride (CNX) films deposited by reactive magnetron sputtering from a graphite target in Ar discharges mixed with N-2 and H-2 at a substrate temperature of 350degreesC have been investigated. Carbon films deposited in pure Ar exhibit a dark resistivity at room temperature of similar to4 X 10(-2) Omegacm, while the resistivity is one order of magnitude lower for CN0.25 films deposited in pure N-2, due to their denser morphology. The increasing H-2 fraction in the discharge gas leads to an increased resistivity for all gas mixtures. This is most pronounced for the nitrogen-free films deposited in an Ar/H-2 mixture, where the resistivity increases by over four orders of magnitude. This can be related to a decreased electron mobility as H inhibits the formation of double bonds. After exposure to air, the resistivity increases with time through two different diffusion regimes. The measured electrical properties of the films are related to the apparent film microstructure, bonding nature, and ambient humidity.
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7.
  • Broitman, E., et al. (författare)
  • Structural and mechanical properties of diamond-like carbon films deposited by direct current magnetron sputtering
  • 2003
  • Ingår i: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - 0734-2101 .- 1520-8559. ; 21:4, s. 851-859
  • Tidskriftsartikel (refereegranskat)abstract
    • A systematic study of physical properties of sputter-deposited DLC films was performed as a function of flux ratio and ion energy. The energy and flux ions and neutral atoms impinging on the surface of the growing films were deduced from Langmuir probe measurements and theoretical calculations. The bombardment of growing films by the energetic particles led to changes in microstructure and mechanical properties. Results suggest that the presence of defective graphite formed by subplanted C and Ar atoms is the dominant influence on the mechanical properties of the DLC films.
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8.
  • Brunell, I.F., et al. (författare)
  • In-situ  stress measurement during the deposition of CN x thin films by unbalanced magnetron sputtering; formation of high levels of stress with 28 eV ion irradiation
  • 2004
  • Ingår i: Philosophical Magazine Letters. - 0950-0839 .- 1362-3036. ; 84:6, s. 395-403
  • Tidskriftsartikel (refereegranskat)abstract
    • Stress development during growth of CN x films by unbalanced magnetron sputtering has been investigated with an in-situ laser deflection technique. The stress is initially tensile, then it becomes compressive, reaching a maximum of as much as 7 GPa. These are anomalously high stress levels compared with pure carbon, considering the low ion energies (28 eV) and ion-to-neutral arrival rate ratio (<1) employed. This phenomenon is explained by the formation of a fullerene-like microstructure and nitrogen substitution at the growth surface. An accompanying increased reactivity of carbon atoms promotes sp3 bonding or other cross-linking of curved basal planes with resulting film densification.
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9.
  • Dantoft, Thomas M., et al. (författare)
  • Gene expression profiling in persons with multiple chemical sensitivity before and after a controlled n-butanol exposure session
  • 2017
  • Ingår i: BMJ Open. - 2044-6055 .- 2044-6055. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure.DESIGN: Participants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure.SETTINGS: Participants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper.PARTICIPANTS: 36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls.OUTCOME MEASURES: 17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels.RESULTS: MCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls.CONCLUSIONS: MCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.
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10.
  • Garcia, I.A., et al. (författare)
  • How hard is fullerene-like CNx? Some observations from the nanoindentation response of a magnetron-sputtered coating
  • 2002
  • Ingår i: Philosophical magazine. A. Physics of condensed matter. Defects and mechanical properties. - 0141-8610. ; 82:10 SPEC., s. 2133-2147
  • Tidskriftsartikel (refereegranskat)abstract
    • Thin fullerene-like CNx coatings deposited on hard substrates (e.g. SiC) show very shallow residual impressions when investigated by nanoindentation at displacements less than the coating thickness. The low work of indentation (i.e. the small area enclosed by the loading and unloading curves) of these materials implies a large amount of recovery of indent depth which is often associated with materials of high hardness. However, analysis of the unloading curves by the Oliver-Pharr method generates hardness values which are usually less than that of silicon. Detailed analysis of the loading curve shows three distinct regimes of behaviour corresponding to behaviour controlled by surface roughness, elastic deformation and plasticity. Measurements of Young's modulus from the elastic part of the loading curve, from the Oliver-Pharr method and from elastic wave measurements are all consistently low. This implies that the material behaves like a very hard rubber which undergoes considerable elastic recovery on unloading but does not have a very high resistance to penetration on loading. The very high H/E values for fullerene-like CNx confirms this view.
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