| 1. |
- Amundadottir, Laufey T., et al.
(författare)
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A common variant associated with prostate cancer in European and African populations
- 2006
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Ingår i: Nature Genetics. - DeCODE Genet, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Urol, IS-101 Reykjavik, Iceland. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:6, s. 652-658
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Tidskriftsartikel (refereegranskat)abstract
- With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
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| 2. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:5, s. 498-502
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P = 1.1 × 10(-11) (rs3204689).
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| 3. |
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| 4. |
- Horn, Armin, et al.
(författare)
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Natural Products from Bryophytes : From Basic Biology to Biotechnological Applications
- 2021
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Ingår i: Critical Reviews in Plant Sciences. - : Informa UK Limited. - 0735-2689 .- 1549-7836. ; 40:3, s. 191-217
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Tidskriftsartikel (refereegranskat)abstract
- Natural products from plants have served mankind in a wide range of applications, such as medicines, perfumes, or flavoring agents. For this reason, synthesis, regulation and function of plant-derived chemicals, as well as the evolution of metabolic diversity, has attracted researchers all around the world. In particular, vascular plants have been subject to such analyses due to prevalent characteristics such as appearance, fragrance, and ecological settings. In contrast, bryophytes, constituting the second largest group of plants in terms of species number, have been mostly overlooked in this regard, potentially due to their seemingly tiny, simple and obscure nature. However, the identification of highly interesting chemicals from bryophytes with potential for biotechnological exploitation is changing this perception. Bryophytes offer a high degree of biochemical complexity, as a consequence of their ecological and genetic diversification, which enable them to prosper in various, often very harsh habitats. The number of bioactive compounds isolated from bryophytes is growing rapidly. The rapidly increasing wealth of bryophyte genetics opens doors to functional and comparative genomics approaches, including disentangling of the biosynthesis of potentially interesting chemicals, mining for novel gene families and tracing the evolutionary history of metabolic pathways. Throughout the last decades, the moss Physcomitrella (Physcomitrium patens) has moved from being a model plant together with Marchantia polymorpha in fundamental biology into an attractive host for the production of biotechnologically relevant compounds such as biopharmaceuticals. In the future, bryophytes like the moss P. patens might also be attractive candidates for the production of novel bryophyte-derived chemicals of commercial interest. This review provides a comprehensive overview of natural product research in bryophytes from different perspectives together with biotechnological advances throughout the last decade.
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| 5. |
- Jóhannesson, Gauti, et al.
(författare)
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Kinetics of γ-cyclodextrin nanoparticle suspension eye drops in tear fluid
- 2014
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Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:6, s. 550-556
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We have developed nanoparticle γ-cyclodextrin dexamethasone (DexNP) and dorzolamide (DorzNP) eye drops that provide sustained high drug concentrations on the eye surface. To test these characteristics, we measured dexamethasone and dorzolamide levels in tear fluid in humans following eye drop administration.METHODS: Concentration of dexamethasone was measured by mass spectrometry. One drop of DexNP was instilled into one eye. Tear fluid was sampled with microcapillary pipettes at seven time-points after drop instillation. Control eyes received Maxidex(®) (dexamethasone). The same procedure was performed for dorzolamide with DorzNP and Trusopt(®) .RESULTS: Six subjects were included in each group. The peak concentration (μg/ml ± standard deviation) of dexamethasone for DexNP eye drops (636.6 ± 399.1) was up to 19-fold higher than with Maxidex(®) (39.3 ± 18.9) (p < 0.001). At 4 hr, DexNP was still 10 times higher than Maxidex(®) . In addition, DexNP resulted in about 30-fold higher concentration of dissolved dexamethasone in the tear fluid of extended time period allowing more drug to partition into the eye tissue. The overall concentration of dorzolamide was about 50% higher for DorzNP (59.5 ± 76.9) than Trusopt(®) (40.0 ± 76.7) (p < 0.05).CONCLUSION: The results indicate high and extended concentration of dissolved dexamethasone with DexNP, which can explain the greater and longer lasting effect of dexamethasone in the cyclodextrin nanoparticle drug delivery platform. Dexamethasone seems to fit the cyclodextrin nanoparticle suspension drug delivery platform with longer duration and higher concentrations in tear fluid than available commercial drops, while dorzolamide is less suitable.
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| 6. |
- Lu, Yi, et al.
(författare)
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Lipidomes of Icelandic bryophytes and screening of high contents of polyunsaturated fatty acids by using lipidomics approach
- 2022
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Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422. ; 206
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Tidskriftsartikel (refereegranskat)abstract
- Bryophytes (mosses, liverworts, and hornworts) have interested researchers because of their high chemical diversity and their potential uses in pharmaceutical, food, and cosmetic industries. Specifically, long-chain polyunsaturated fatty acids (l-PUFA) such as arachidonic acid (AA) and eicosapentaenoic acid (EPA) are commonly found in bryophytes, but not in vascular plants. Bryophytes accumulate PUFAs in cold or even freezing temperature to keep the cell fluidity. Iceland has a long history of bryophyte vegetation. These bryophytes are highly adapted to the harsh environment in Iceland and therefore are expected to produce high amounts of PUFAs. However, despite the fact that hundreds of mosses and liverworts have been found in Iceland, their lipid profiles largely remain unknown. In this study, we performed untargeted lipidomics by using UPLC-ESI-QTOF-MS as a rapid screening strategy to examine the lipid compositions of 39 local bryophyte species in Iceland and aimed to find high AA and EPA producers. A total of 280 lipid molecular species from 15 lipid classes were quantified with isotope-labeled internal standards. AA and EPA were abundantly distributed in the phospholipids (mainly PC and PE) and glycerolipids (MGDG and DGDG) in six moss species, namely Racomotrium lanuginosum, R. ericoides, Bryum psedotriquetrium, Plagiomnium ellipticum, Hylocomium splendens, and Rhytidiadelphus triquetrus. Two of the six species (B. psedotriquetrium and H. splendens) also accumulated high concentrations of PUFA-containing-triacylglycerols.
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| 7. |
- Sigurbergsdottir, Adalbjorg Yr, et al.
(författare)
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Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts: results from the population-based iStopMM study
- 2023
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Ingår i: REVISTA CHILENA DE LITERATURA. - 0718-2295. ; :108, s. 3392-3398
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with re-gards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumato-logical disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.
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| 8. |
- Thorgeirsson, Thorgeir E, et al.
(författare)
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A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7187, s. 9-638
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
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| 9. |
- Thorsteinsdóttir, Margrét
(författare)
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Separation of peptides by capillary electrophoresis : Application of chemometrics for evaluation of separation performance in micellar electrokinetic chromatography
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The separation of enkephalin-related peptides and protein kinase A peptide substrates werestudied in micellar electrokinetic chromatography and compared with capillary zoneelectrophoresis. Special interest was focused on systems where the electroosmosis wasreversed in combination with neutral micellar agents. Such systems involve the unique combination of minimizing surface interactions by electrostatic effects and increasing themigration time window. This was accomplished either by addition of cationic monomericamines to the background electrolyte or by using fused silica capillaries modified byimmobilizing an amine to the surface.The selectivities were enhanced by adding anionic taurodeoxycholate micelles to the BGE.The efficiencies obtained were highly dependent on the extent of distribution of the peptides tothe micellar phase. The effect of experimental factors that cause band broadening duringseparation were evaluated by fractional factorial design and response surface modelling. Partialleast square (PLS) regression analysis revealed that very high efficiencies were obtained forpeptides with low distribution to the micelles, while the efficiencies drastically decreased forpeptides strongly associated to the micelles, probably due to slow sorption-desorption kinetics.The separation of enkephalin-related peptides in a system with anionic sodium dodecylmicelles (SDS) was optimized by utilizing experimental design and response surfacemodelling. Such strategies have the advantages of greatly reducing the number of experimentsand allowing identification of interaction effects between the variables. The effect ofacetonitrile was studied, in four different concentration domains, together with SDSconcentration, temperature and the ionic strength of the buffer via central composite design,and related to resolution, migration factor and migration time window utilizing PLS-regression. The results revealed a complex system with very different influences of theexperimental variables in respective domain. The effect of acetonitrile is highly non-linear insystems of this kind and dependent on the temperature used. A change in the thermodynamicsof the distribution behaviour was observed at increasing acetonitrile concentrations. Further,the relationships between different parameters that influence the resolution were investigatedby principal component analysis.
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| 10. |
- Zhou, Yuye
(författare)
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Analysis of proteins related toautoimmune and inflammatorydiseases with focus on newenrichment methodologies and MALDI-TOF MS
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteins have been widely studied in biological sample analysis due to the association with diseases. In the present project, method and technique development was carried out on the analysis of two proteins, immunoglobulin G (IgG) and osteopontin (OPN). The changes in IgG glycosylation, and elevated plasma OPN levels have been reported to be associated with chronic inflammation and autoimmune diseases.Lab synthesized zeolitic imidazolate framework (ZIF) nanocomposites (paper I) and environmentally friendly wood materials (paper II) were successfully utilized for IgG glycopeptide enrichment in order to eliminate the interference caused by non‑glycopeptides. The quantification and identification of glycopeptides by matrix assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS) was simplified using label-free internal standard, and intact glycopeptide identification without glycan release. The separation of enriched glycopeptides was further studied on capillary electrophoresis.Due to the low abundance of OPN in plasma, preconcentration of OPN is required prior to MS analysis. In paper III, a fast, cheap and antibody-free method was developed for recombinant human OPN (rhOPN) preconcentration from a complex mixture, human plasma, together with MALDI-TOF/TOF MS identification.In proteomics, enzymatic digestion of proteins is a very common step. In paper IV, the utilization of thiol-ene microchips (TE microchip) immobilized with trypsin provided fast digestion with residence time of only 10 s. Furthermore, the TE microchip linked with ascorbic acid could be used for IgG glycopeptide enrichment. These applications made TE microchips ready for multifunctional tasks in proteomics.Methods and techniques developed in the present project can be applied in the future for the study of biological samples, to investigate the possible relation between these proteins and autoimmune and inflammatory diseases, as well as other related diseases.
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