| 81. |
- Erriah, M., et al.
(author)
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Galectin-3 enhances monocyte-derived macrophage efferocytosis of apoptotic granulocytes in asthma
- 2019
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In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-993X. ; 20
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Journal article (peer-reviewed)abstract
- BackgroundGalectin-3 is a 32kDa protein secreted by macrophages involved in processes such as cell activation, chemotaxis and phagocytosis. Galectin-3 has previously been shown to improve the ability of airway macrophages to ingest apoptotic cells (efferocytosis) in chronic obstructive pulmonary disease (COPD) and may be of interest in non-eosinophilic asthma (NEA) which is also characterised by impaired efferocytosis. It was hypothesised that the addition of exogenous galectin-3 to monocyte-derived macrophages (MDMs) derived from donors with NEA would enhance their ability to engulf apoptotic granulocytes.MethodsEligible non-smoking adults with asthma (n=19), including 7 with NEA and healthy controls (n=10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50g/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array.ResultsBaseline efferocytosis (mean (standard deviation)) was lower in participants with asthma (33.2 (+/- 17.7)%) compared with healthy controls (45.3 (+/- 15.9)%; p=0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (+/- 19.2)%) and NEA (28.7 (+/- 21.5)%; p=0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (+/- 18.1)%) compared with baseline (30.4 (+/- 19.7)%; p=0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r=-0.671; p=0.017). Galectin-3 was diffusely distributed in most MDMs but formed punctate structures in 5% of MDMs. MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p=0.044) while IL-6 and CXCL8 levels were similar.Conclusions p id=Par4 Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.
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| 82. |
- Fall, Tove, et al.
(author)
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The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
- 2013
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
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Journal article (peer-reviewed)abstract
- Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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| 84. |
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| 85. |
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| 86. |
- Graslund, S, et al.
(author)
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Protein production and purification
- 2008
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In: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 5:2, s. 135-146
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Journal article (peer-reviewed)
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| 87. |
- Hallberg, Josef, et al.
(author)
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HomeRuleML : a model for the exchange of decision support rules within smart environments
- 2007
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In: IEEE International Conference on Automation Science and Engineering, 2007. - Piscataway, NJ : IEEE Communications Society. - 1424411548 - 9781424411542 ; , s. 513-520
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Conference paper (peer-reviewed)abstract
- The demands for smart environments, which can help to facilitate as well as monitor independent living are increasing. With this comes a desire for decision support rules to process data recorded from such environments. However, testing and evaluating rules can be both time-consuming and indeed stressful for the inhabitants. Within this paper we propose a model, referred to as HomeRuleML, for representing decision support rules for smart environments. The motivating factor behind such a proposal is to provide a widely and freely accessible set of rules which can be openly used and exchanged within the research domain and beyond. This model has the potential to decrease the time required for deployment, and inevitability improve the inhabitants' quality of life. In the paper we explain in detail the structure of adopting this approach and also provide an indication of the typical types of software tools required for its use.
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| 88. |
- Jallow, Muminatou, et al.
(author)
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Genome-wide and fine-resolution association analysis of malaria in West Africa.
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; , s. 657-665
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Journal article (peer-reviewed)abstract
- We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 x 10(-7) to P = 4 x 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
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| 89. |
- Lappalainen, Tuuli, et al.
(author)
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Transcriptome and genome sequencing uncovers functional variation in humans
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 506-511
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Journal article (peer-reviewed)abstract
- Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project-the first uniformly processed high-throughput RNA-sequencing data from multiple human populations with high-quality genome sequences. We discover extremely widespread genetic variation affecting the regulation of most genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on the cellular mechanisms of regulatory and loss-of-function variation, and allows us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome.
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