| 131. |
|
|
| 132. |
- Reksten, Tove Ragna, et al.
(författare)
-
Genetic associations to germinal centre formation in primary Sjögren's syndrome
- 2014
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 73:6, s. 1253-1258
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune rheumatic disease mainly characterised by focal mononuclear cell infiltration in the salivary and lacrimal glands, and by the symptoms xerostomia and keratoconjunctivitis sicca. Germinal centre-like structures (GC) are found in the minor salivary glands of approximately 25% of patients. In this study, we aimed to assess genetic variations in pSS patients with GC-like formations (GC+) compared with patients without such formations (GC−).MethodsMinor salivary gland biopsies from Swedish and Norwegian pSS patients (n=320) were evaluated for GC-like formations, identifying 76 GC+ and 244 GC− patients. A panel of 1536 single-nucleotide polymorphisms (SNPs) in 107 genes was genotyped. Minor allele frequencies in GC+ and GC− patients were compared using Fisher's exact test, and associations were considered significant when p<4.7×10−4 and suggestive when p<0.01.ResultsIn this case-only analysis, we identified two SNPs in CCL11 (eotaxin) associated with GC-like structures (p<4.7×10−4, OR 0.45 and 0.41, respectively). A haplotype of the two minor alleles was associated with GC status with p=2.6×10−4, OR 0.40. Suggestive associations (p<0.01) were found in SNPs in the B cell activation and/or GC-formation related genes AICDA, BANK1 and BCL2. Furthermore, SNPs in IL17A, ICA1, PKN1 and SNPs in the NF-κB pathway genes CARD8, IKBKE and TANK were found suggestively associated with GC-like structures.ConclusionsOur findings suggest that genetic variations may explain why ectopic GC-like structures are present in some pSS patients, and support the hypothesis that GC+ and GC− patients represent distinct disease phenotypes.
|
|
| 133. |
- Reynolds, P., et al.
(författare)
-
Latitude, temperature and habitat complexity predict predation pressure in eelgrass beds across the Northern Hemisphere
- 2018
-
Ingår i: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 99:1, s. 29-35
-
Tidskriftsartikel (refereegranskat)abstract
- Latitudinal gradients in species interactions are widely cited as potential causes or consequences of global patterns of biodiversity. However, mechanistic studies documenting changes in interactions across broad geographic ranges are limited. We surveyed predation intensity on common prey (live amphipods and gastropods) in communities of eelgrass (Zostera marina) at 48 sites across its Northern Hemisphere range, encompassing over 370 of latitude and four continental coastlines. Predation on amphipods declined with latitude on all coasts but declined more strongly along western ocean margins where temperature gradients are steeper. Whereas in situ water temperature at the time of the experiments was uncorrelated with predation, mean annual temperature strongly positively predicted predation, suggesting a more complex mechanism than simple increased metabolic activity at the time of predation. This large-scale biogeographic pattern was modified by local habitat characteristics; predation declined with higher shoot density both among and within sites. Predation rates on gastropods, by contrast, were uniformly low and varied little among sites. The high replication and geographic extent of our study not only provides additional evidence to support biogeographic variation in intensity, but also insight into the mechanisms that relate temperature and biogeographic gradients in species interactions.
|
|
| 134. |
- Räikkönen, Katri, et al.
(författare)
-
Insulin, Glucose, and the Metabolic Syndrome in Cardiovascular Behavioral Medicine
- 2022
-
Ingår i: Handbook of Cardiovascular Behavioral Medicine. - New York, NY : Springer New York. - 9780387859606 - 9780387859590 ; , s. 809-831
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- It has been known for decades that risk factors for diabetes and cardiovascular disease (CVD) tend to cluster. Metabolic syndrome refers to this risk factor clustering for some of the more well-established and dangerous risk factors. This chapter provides a historical overview on the concept of the metabolic syndrome; describes the clinical criteria used in the definition of the metabolic syndrome and how to measure components of the metabolic syndrome, emphasizing measurements related to insulin and glucose; provides a brief overview of the genetic, endocrine, and early life determinants of the metabolic syndrome; and presents findings from studies that have focused on psychological correlates, determinants, and consequences of the metabolic syndrome, focusing in particular on psychosocial stress and depression.
|
|
| 135. |
- Scott, Robert A., et al.
(författare)
-
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
- 2017
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
-
Tidskriftsartikel (refereegranskat)abstract
- To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
|
|
| 136. |
- Sepulveda, Jorge I. Ramirez, et al.
(författare)
-
Long-term follow-up in primary Sjögren's syndrome reveals differences in clinical presentation between female and male patients
- 2017
-
Ingår i: Biology of Sex Differences. - : BioMed Central. - 2042-6410. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Despite men being less prone to develop autoimmune diseases, male sex has been associated with a more severe disease course in several systemic autoimmune diseases. In the present study, we aimed to investigate differences in the clinical presentation of primary Sjogren's syndrome (pSS) between the sexes and establish whether male sex is associated with a more severe form of long-term pSS. Methods: Our study population included 967 patients with pSS (899 females and 68 males) from Scandinavian clinical centers. The mean follow-up time (years) was 8.8 +/- 7.6 for women and 8.5 +/- 6.2 for men (ns). Clinical data including serological and hematological parameters and glandular and extraglandular manifestations were compared between men and women. Results: Male patient serology was characterized by more frequent positivity for anti-Ro/SSA and anti-La/SSB (p = 0. 02), and ANA (p = 0.02). Further, men with pSS were more frequently diagnosed with interstitial lung disease (p = 0. 008), lymphadenopathy (p = 0.04) and lymphoma (p = 0.007). Conversely, concomitant hypothyroidism was more common among female patients (p = 0.009). Conclusions: We observe enhanced serological responses and higher frequencies of lymphoma-related extraglandular manifestations in men with pSS. Notably, lymphoma itself was also significantly more common in men. These observations may reflect an aggravated immune activation and a more severe pathophysiological state in male patients with pSS and indicate a personalized managing of the disease due to the influence of the sex of patients with pSS.
|
|
| 137. |
- Sohail, Hafiz Muhammad, et al.
(författare)
-
First principles study of electronic and atomic structures of a √3x√3 superstructures induced by Ag on Si(111) and Ge(111)
- 2014
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We have employed first principles density functional theory (DFT) based calculations (WIEN2k) to study the electronic and atomic structures of the reconstruction induced by Ag on Si(111) and Ge(111). The Ag/Si(111) surface, in particular, has acted as a model system when it comes to the interaction between adsorbed metals and semiconductor surfaces. Two models have been studied, i.e., the honeycomb-chained-triangle (HCT) and the in-equivalenttriangle (IET) model. The band structures of these models were calculated using density functional theory within the generalized gradient approximation (GGA) and the local density approximation (LDA). The band structures calculated from the fully relaxed versions of the two models were found to be quite similar except for the occupancy of the free electron like band at the - point. The IET model gives a slightly lower energy minimum compared to the HCT model for both Si and Ge. Further, we find that the energy minima are deeper for Ge when comparing the results with Si for the HCT and IET models, respectively. The theoretical surface band structure is qualitatively in good general agreement with the experimental dispersions of the main surface states, while the theoretical band widths are approximately half of the experimental ones. The calculated band structures show a gap between the two uppermost, fully occupied, bands at the - point only when the IET model is used to account for the electronic structure of Ag/Si(111) . Neither the IET nor the HCT model resulted in a gap when applied to Ag/Ge(111) .
|
|
| 138. |
- Stancar, Z., et al.
(författare)
-
Experimental validation of an integrated modelling approach to neutron emission studies at JET
- 2021
-
Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 61:12
-
Tidskriftsartikel (refereegranskat)abstract
- An integrated modelling methodology for the calculation of realistic plasma neutron sources for the JET tokamak has been developed. The computational chain comprises TRANSP plasma transport and DRESS neutron spectrum calculations, and their coupling to the MCNP neutron transport code, bridging plasma physics and neutronics. In the paper we apply the developed methodology to the analysis of neutron emission properties of deuterium and helium plasmas at JET, and validate individual modelling steps against neutron diagnostic measurements. Two types of JET discharges are modelled-baseline-like and three-ion radio-frequency scenarios-due to their diversity in plasma heating, characteristics of the induced fast ion population, and the imprint of these on neutron emission properties. The neutron emission modelling results are quantitatively compared to the total neutron yield from fission chambers, neutron emissivity profiles from the neutron camera, neutron spectra from the time-of-flight spectrometer, and neutron activation measurements. The agreement between measured and calculated quantities is found to be satisfactory for all four diagnostic systems within the estimated experimental and computational uncertainties. Additionally, the effect of neutrons not originating from the dominating D(D, n)He-3 reactions is studied through modelling of triton burnup DT neutrons, and, in mixed D-He-3 plasmas, neutrons produced in the Be-9(D, n gamma)B-10 reaction on impurities. It is found that these reactions can contribute up to several percent to the total neutron yield and dominate the neutron activation of samples. The effect of MeV-range fast ions on the neutron activation of In-115 and Al-27 samples is measured and computationally validated.
|
|
| 139. |
- Strawbridge, Rona J., et al.
(författare)
-
Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation
- 2017
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 266, s. 196-204
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.
|
|
| 140. |
- Taal, H. Rob, et al.
(författare)
-
Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
-
Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
|
|
