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| 2. |
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| 3. |
- Asselbergs, Folkert W., et al.
(författare)
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Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
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| 4. |
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| 5. |
- Postmus, Iris, et al.
(författare)
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Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
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| 6. |
- Ilieva, S., et al.
(författare)
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Coulomb excitation of neutron-rich Cd isotopes
- 2014
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 89:1
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Tidskriftsartikel (refereegranskat)abstract
- The isotopes (122),(124),Cd-126 were studied in a "safe" Coulomb-excitation experiment at the radioactive ion-beam facility REX-ISOLDE at CERN. The reduced transition probabilities B(E2; 0(g. s)(vertical bar) -> 2(1)(+)) and limits for the quadrupole moments of the first 2(+) excited states in the three isotopes were determined. The onset of collectivity in the vicinity of the Z = 50 and N = 82 shell closures is discussed by comparison with shell model and beyond mean-field calculations.
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| 7. |
- Roy, Sushmita, et al.
(författare)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Tidskriftsartikel (refereegranskat)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 8. |
- Weber, H., et al.
(författare)
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The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis
- 2014
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 24:1, s. 65-85
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Tidskriftsartikel (refereegranskat)abstract
- NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. (C) 2013 Elsevier B.V. and ECNP. All rights reserved.
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| 9. |
- Assimes, Themistocles L., et al.
(författare)
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Lack of Association Between the Trp719Arg Polymorphism in Kinesin-Like Protein-6 and Coronary Artery Disease in 19 Case-Control Studies
- 2010
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:19, s. 1552-1563
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Tidskriftsartikel (refereegranskat)abstract
- Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. (J Am Coll Cardiol 2010;56:1552-63) (C) 2010 by the American College of Cardiology Foundation
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| 10. |
- Donahue, N. M., et al.
(författare)
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Aging of biogenic secondary organic aerosol via gas-phase OH radical reactions
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:34, s. 13503-13508
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Tidskriftsartikel (refereegranskat)abstract
- The Multiple Chamber Aerosol Chemical Aging Study (MUCHACHAS) tested the hypothesis that hydroxyl radical (OH) aging significantly increases the concentration of first-generation biogenic secondary organic aerosol (SOA). OH is the dominant atmospheric oxidant, and MUCHACHAS employed environmental chambers of very different designs, using multiple OH sources to explore a range of chemical conditions and potential sources of systematic error. We isolated the effect of OH aging, confirming our hypothesis while observing corresponding changes in SOA properties. The mass increases are consistent with an existing gap between global SOA sources and those predicted in models, and can be described by a mechanism suitable for implementation in those models.
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| 11. |
- Peloso, Gina M, et al.
(författare)
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Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
- 2014
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
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| 12. |
- Treusch, Sebastian, et al.
(författare)
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Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast
- 2011
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Ingår i: Science. - Washington : American association of advancement in science. - 0036-8075 .- 1095-9203. ; 334:6060, s. 1241-1245
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Tidskriftsartikel (refereegranskat)abstract
- Aβ (beta amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained using yeast as a model system.
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| 13. |
- Franke, Andre, et al.
(författare)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 14. |
- Naylor, Mary D, et al.
(författare)
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Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations from the Ware Invitational Summit.
- 2012
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 8:5, s. 445-52
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Tidskriftsartikel (refereegranskat)abstract
- To address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled "State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care," on June 21-22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article.
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| 15. |
- Eliasson, Kent, et al.
(författare)
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All in the Family : self Selection and Migration by Couples
- 2014
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Ingår i: Papers in regional science (Print). - : John Wiley & Sons. - 1056-8190 .- 1435-5957. ; 93:1, s. 101-124
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines determinants of couple migration in a model that accounts for self-selection of migrant couples. The study is based on a sample of married couples from the Swedish population. The model incorporates controls for earnings of both spouses preceding the move, and explicitly addresses unmeasured heterogeneity in the family decision to migrate. Two statistical formulations are presented. In the first version, migration is measured as a dichotomous move/stay decision. A second formulation replaces the dichotomous indicator with the distance moved by migrants. Results suggest that family migration is selective of relatively low earning wives with unmeasured potential for strong earnings.
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| 16. |
- Furberg, Helena, et al.
(författare)
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Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
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Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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| 17. |
- Landström, Fredrik J., 1966-, et al.
(författare)
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Electroporation therapy for T1 and T2 oral tongue cancer
- 2011
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Ingår i: Acta Oto-Laryngologica. - : Informa Healthcare. - 0001-6489 .- 1651-2251. ; 131:6, s. 660-664
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Electroporation therapy appears to be a safe treatment achieving excellent local tumor control and very good functional results in our study and it should be further clinically evaluated.Objectives: The objectives of this study were to assess local tumor control, survival, and effects on speech and eating after treatment of tongue cancer with electroporation therapy, a new local therapeutic modality. In this approach intracellular accumulation of a chemotherapeutic agent is achieved by using a locally applied electrical field.Methods: Fifteen patients with primary T1 and T2 oral tongue cancer were treated with electroporation therapy with intratumorally administered bleomycin. Postoperative radiotherapy was performed when the tumor infiltration was 5 mm or more. The follow-up time was 24 months for the surviving patients and 20.4 months overall. The effects on eating and speech were assessed using the PSS-HN scale and voice recordings.Results: No local recurrence was recorded in any patient during the follow-up. Three patients died, two from progressive regional disease. Of the 12 surviving patients, 2 patients had regional recurrence and 10 patients including the 5 patients treated with EPT alone were tumor-free both locally and regionally at the last follow-up. The functional outcome for speech and eating were very good.
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| 18. |
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| 19. |
- Taylor, M. J., et al.
(författare)
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Isospin symmetry in the odd-odd mirror nuclei (44)V/(44)Sc
- 2011
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:6
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Tidskriftsartikel (refereegranskat)abstract
- Excited states in the N = Z - 2 nucleus (44)V have been observed for the first time. The states have been identified through particle-gamma-gamma coincidence relationships and comparison with analog states in themirror nucleus (44)Sc. Mirror energy differences have been extracted and compared to state-of-the-art shell-model calculations which include charge-symmetry-breaking forces. Observed decay pattern asymmetries between the mirror pair are discussed in terms of core excitations, electromagnetic spin-orbit effects and isospin mixing.
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| 20. |
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| 21. |
- Broitman, Esteban, 1958-, et al.
(författare)
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Comparative study on the properties of ZnO nanowires and nanocrystalline thin films
- 2012
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 213, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- The microstructural, morphological, optical and water-adsorption properties of nanocrystalline ZnO thin films and ZnO nanowires were studied and compared. The ZnO thin films were obtained by a sol–gel process, while the ZnO nanowires were electrochemically grown onto a ZnO sol–gel spin-coated seed layer. Thin films and nanowire samples were deposited onto crystalline quartz substrates covered by an Au electrode, able to be used in a quartz crystal microbalance. X-ray diffraction measurements reveal in both cases a typical diffraction pattern of ZnO wurtzite structure. Scanning electron microscopic images of nanowire samples show the presence of nanowires with hexagonal sections, with diameters ranging from 30 to 90 nm. Optical characterization reveals a bandgap energy of 3.29 eV for the nanowires and 3.35 eV for the thin films. A quartz crystal microbalance placed in a vacuum chamber was used to quantify the amount and kinetics of water adsorption onto the samples. Nanowire samples, which have higher surface areas than the thin films, adsorb significantly more water.
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| 22. |
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| 23. |
- Fossos-Wong, Nicole, et al.
(författare)
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Changes in Alcohol Expectancies, Drinking and Alcohol-Related Negative Consequences in the Transition out of High School
- 2014
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Ingår i: Alcoholism. - : John Wiley & Sons. - 0145-6008 .- 1530-0277. ; 38:s1, s. 59A-59A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The transition fromadolescence to emerging adulthood is a period of increased risk for heavy drinking behavior. Prior research has found that college students drink more and experience more consequences than their non-college counterparts. However, sparse research has examined whether students who are college- versus work-bound show differences in drinking and related consequences in high school (HS) as well. In addition, little research has explored whether alcohol expectancies also change over time as a function of selection into college versus non-college environments. The current study examined whether alcohol-related expectancies, consequences, and drinking changed over the course of a year as a function of whether participants transitioned into a four-year university (UNI), community college/trade school (CC), or workforce setting (WF). Participants (N=848) were HS seniors (mean age=17.5 years; 37%male, 73%Caucasian) taking part in a larger study examining alcohol use trajectories.Measures included alcohol expectancies (CEOA), drinking (DDQ), and alcohol-related problems (RAPI) assessed during their senior year and one year later. Repeatedmeasures ANOVAs revealed significant main effects for time, indicating increases in drinks per week F(1, 807)=19.18, p>0.001 and alcohol-related problems F(1, 808)=8.78, p>0.01 and a decrease in alcohol expectancies F(1, 808)=14.35, p>0.001 from baseline to 12 month follow-up. Results also found a main effect for group, indicating UNI students held higher expectancies F(2, 808)=8.15, p>0.001 and drank more F(2, 807)=6.26, p>0.01 than other participants. A significant time9group interaction showed that whereas UNI-bound students drank less thanWF-bound students in HS, the roles reversed one year later with UNI students drinking more thanWF students F (2, 807)=27.56, p>0.001. Similarly, WF-bound students had more alcohol-related problems in HS followed by CC-bound students and UNI-bound students, but one year later the order reversed with UNI students exhibiting the most alcohol-related problems F(2, 807)=5.21, p>0.01. Results indicate that whereas UNI-bound seniors exhibit the highest expectancies, drink less, and experience fewer problems during HS, upon entry into UNI, they experience more problems and out-drink their CC andWF counterparts. These results highlight the importance of prevention strategies, including an expectancy challenge component, especially for UNI-bound HS seniors.
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| 24. |
- Goodson, J. M., et al.
(författare)
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Control of periodontal infections: A randomized controlled trial I. The primary outcome attachment gain and pocket depth reduction at treated sites
- 2012
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Ingår i: Journal of Clinical Periodontology. - 0303-6979. ; 39:6, s. 526-536
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare the treatment outcome of scaling and root planing (SRP) in combination with systemic antibiotics, local antibiotic therapy and/or periodontal surgery. Material and Methods One hundred and eighty-seven patients were assigned to eight groups treated by SRP plus none, one, two or three adjunctive treatments and monitored for 24 similar to months in a randomized controlled clinical trial using a 2 similar to 2 similar to 2 factorial design. Systemic amoxicillin similar to metronidazole (SMA), local tetracycline delivery (LTC) and periodontal surgery (SURG) were evaluated as adjuncts. Changes in clinical attachment level (CAL) and probing pocket depth (PPD) were statistically evaluated by ancova of main effects. Results Effects of adjunctive therapy to SRP were minimal at 3 similar to months. Between 3 and 6 similar to months PPD reduction occurred particularly in patients receiving periodontal surgery. After 6 similar to months, both CAL gain and PPD reduction reached a plateau that was maintained at 24 similar to months in all groups. The 24-month CAL gain was improved by SMA (0.50 similar to mm) while PPD was reduced by SMA (0.51 similar to mm) and SURG (0.36 similar to mm). Smoking reduced CAL gain and PPD reduction. Conclusion Patients receiving adjunctive therapies generally exhibited improved CAL gain and/or PPD reduction when compared with the outcome of SRP alone. Only additive, not synergistic effects of the various adjunctive therapies were observed.
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| 25. |
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| 26. |
- Jungersted, Jakob Mutanu, et al.
(författare)
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In vivo studies of aquaporins 3 and 10 in human stratum corneum.
- 2013
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Ingår i: Archives of dermatological research. - : Springer Science and Business Media LLC. - 1432-069X .- 0340-3696. ; 305:8, s. 699-704
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Tidskriftsartikel (refereegranskat)abstract
- Aquaporins (AQPs) constitute one family of transmembrane proteins facilitating transport of water across cell membranes. Due to their specificity, AQPs have a broad spectrum of physiological functions, and for keratinocytes there are indications that these channel proteins are involved in cell migration and proliferation with consequences for the antimicrobial defense of the skin. AQP3 and AQP10 are aqua-glyceroporins, known to transport glycerol as well as water. AQP3 is the predominant AQP in human skin and has previously been demonstrated in the basal layer of epidermis in normal human skin, but not in stratum corneum (SC). AQP10 has not previously been identified in human skin. Previous studies have demonstrated the presence of AQP3 and AQP10 mRNA in keratinocytes. In this study, our aim was to investigate if these aquaporin proteins were actually present in human SC cells. This can be seen as a first step toward elucidating the possible functional role of AQP3 and AQP10 in SC hydration. Specifically we investigate the presence of AQP3 and AQP10 in vivo in human SC using "minimal-invasive" technique for obtaining SC samples. SC samples were obtained from six healthy volunteers. Western blotting and immunohistochemistry were used to demonstrate the presence of AQP3 as well as AQP10. The presence of AQP3 and AQP10 was verified by Western blotting, allowing for detection of proteins by specific antibodies. Applying immunohistochemistry, cell-like structures in the shape of corneocytes were identified in all samples by AQP3 and AQP10 antibodies. In conclusion, identification of AQP3 and AQP10 protein in SC in an in vivo model is new. Together with the new "minimal-invasive" method for SC collection presented, this opens for new possibilities to study the role of AQPs in relation to function of the skin barrier.
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| 27. |
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| 28. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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A high-resolution map of human evolutionary constraint using 29 mammals
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 478:7370, s. 476-482
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Tidskriftsartikel (refereegranskat)abstract
- The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering similar to 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for similar to 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate-and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.
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| 29. |
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| 30. |
- McGovern, Dermot P B, et al.
(författare)
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Genome-wide association identifies multiple ulcerative colitis susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:4, s. 332-337
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Tidskriftsartikel (refereegranskat)abstract
- Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan, comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5). Seven of these loci exceeded genome-wide significance (P < 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis.
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| 31. |
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| 32. |
- Olofsson, Niclas, et al.
(författare)
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Long-term health consequences of violence exposure in adolescence : A 26–year prospective study
- 2012
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Ingår i: BMC Public Health. - London : Springer Science and Business Media LLC. - 1471-2458. ; 12:411
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Tidskriftsartikel (refereegranskat)abstract
- Background: Violence victimization represents a serious risk factor for health related symptoms, for both men and women. The aim of this study was to evaluate the long-term effects of violence exposure in late adolescence and early adulthood on adult health, physical as well as mental, using a long-term prospective population-based study, with a follow up of 9, 19, and 26 years.Methods: The primary data source is a longitudinal panel from one of the longest running social science surveys in the world, the Swedish Level-of-Living surveys (LNU). We analyzed three cohorts, individuals aged 15-19 in 1974 and 1981, and individuals aged 18-19 in 1991 which were followed up 2000. Structured interviews on childhood, family relationships, life-events, living conditions, health history and status, working conditions, behavioral, psychosocial, and demographic variables were repeatedly used in all cohorts.Results: Multivariate models of violence exposures in adolescence in the 1974-91 cohorts as predictors of adult health in 2000 are reported for both men and women. Women exposed to violence had raised odds ratios for ill health, measured as heavy illness burden, and poor self rated health, after controlling for possible confounders. No such associations were found for men.Conclusions: This study’s findings provide additional empirical support for the importance of policies and practices to identify and prevent violence exposure in adolescence and young adulthood and to supply treatments for adolescence exposed to violence and above all the young women.
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| 33. |
- Sandberg, Kenneth, 1945, et al.
(författare)
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Fetal nicotine exposure increases airway responsiveness and alters airway wall composition in young lambs.
- 2011
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Ingår i: Respiratory physiology & neurobiology. - : Elsevier BV. - 1878-1519 .- 1569-9048. ; 176:1-2, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- To test the hypotheses that fetal nicotine exposure alters airway wall composition and enhances the airway response to inhaled methacholine (MCh), lambs were exposed during the last fetal trimester to (1) a low dose (LN) (n=13, 0.5mg/kg/d (maternal weight) of free base nicotine, (2) a moderate dose (MN) (n=10, 1.5mg/kg/d) or (3) saline (n=14). Studies were performed at postnatal days 12, 26 and 52. Prenatal nicotine exposure induced a dose- and age-related hyper-responsiveness to MCh in the proximal airways. Moment analysis of nitrogen decay curves showed no nicotine or MCh effects on ventilation homogeneity or gas-mixing efficiency in the distal airways during MCh inhalations suggesting a bimodal response. Fetal nicotine exposure increased epithelial mucosubstance volume in central (LN, MN) and distal bronchi (LN), increased smooth muscle volume in distal bronchi and bronchioles (LN) and decreased bronchiolar diameter (MN). In conclusion, third trimester nicotine exposure causes hyperreactive proximal airways and alters proximal airway wall composition associated with airflow limitation.
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| 34. |
- Selig, Elizabeth R, et al.
(författare)
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Global priorities for marine biodiversity conservation.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- In recent decades, many marine populations have experienced major declines in abundance, but we still know little about where management interventions may help protect the highest levels of marine biodiversity. We used modeled spatial distribution data for nearly 12,500 species to quantify global patterns of species richness and two measures of endemism. By combining these data with spatial information on cumulative human impacts, we identified priority areas where marine biodiversity is most and least impacted by human activities, both within Exclusive Economic Zones (EEZs) and Areas Beyond National Jurisdiction (ABNJ). Our analyses highlighted places that are both accepted priorities for marine conservation like the Coral Triangle, as well as less well-known locations in the southwest Indian Ocean, western Pacific Ocean, Arctic and Antarctic Oceans, and within semi-enclosed seas like the Mediterranean and Baltic Seas. Within highly impacted priority areas, climate and fishing were the biggest stressors. Although new priorities may arise as we continue to improve marine species range datasets, results from this work are an essential first step in guiding limited resources to regions where investment could best sustain marine biodiversity.
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| 35. |
- Svartvik, Jesper, et al.
(författare)
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Rendering the Rending of the Veil: What Difference Does It Make?
- 2012
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Ingår i: Making a Difference: Essays on the Bible and Judiams in Honor fo Tamara Cohn Eskenazi. - 9781907534720 ; , s. 257-276
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Bokkapitel (refereegranskat)abstract
- This article explores how the NT accounts of the rending of the veil in the Temple at the time of Jesus have been interpreted: as a sign of wrath, joy and grief.
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| 36. |
- Taylor, M. J., et al.
(författare)
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First Gamma-Ray Spectroscopy and Isospin Symmetry Study of the N = Z-2 Nucleus V-44
- 2010
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Ingår i: Modern Physics Letters A. - 0217-7323. ; 25:21-23, s. 2028-2029
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Konferensbidrag (refereegranskat)abstract
- Excited states in the T-z = -1 nucleus V-44 have been observed for the first time. The states have been identified through recoil-gamma-gamma coincidences and comparison with analogue states in the mirror nucleus Sc-44. Mirror energy differences have been extracted and compared to state-of-the-art fp shell-model calculations which include charge symmetry breaking forces.
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| 37. |
- Turner, Stephen T., et al.
(författare)
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Genomic Association Analysis of Common Variants Influencing Antihypertensive Response to Hydrochlorothiazide
- 2013
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Ingår i: Hypertension. - 1524-4563. ; 62:2, s. 391-397
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes influencing blood pressure response to thiazide diuretic therapy for hypertension, we conducted genome-wide association meta-analyses of approximate to 1.1 million single-nucleotide polymorphisms in a combined sample of 424 European Americans with primary hypertension treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses study (n=228) and the Genetic Epidemiology of Responses to Antihypertensive study (n=196). Polymorphisms associated with blood pressure response at P<10(-5) were tested for replication of the associations in independent samples of hydrochlorothiazide-treated European hypertensives. The rs16960228 polymorphism in protein kinase C, replicated for same-direction association with diastolic blood pressure response in the Nordic Diltiazem study (n=420) and the Genetics of Drug Responsiveness in Essential Hypertension study (n=206), and the combined 4-study meta-analysis P value achieved genome-wide significance (P=3.3x10(-8)). Systolic or diastolic blood pressure responses were consistently greater in carriers of the rs16960228 A allele than in GG homozygotes (>4/4 mm Hg) across study samples. The rs2273359 polymorphism in the GNAS-EDN3 region also replicated for same-direction association with systolic blood pressure response in the Nordic Diltiazem study, and the combined 3-study meta-analysis P value approached genome-wide significance (P=5.5x10(-8)). The findings document clinically important effects of genetic variation at novel loci on blood pressure response to a thiazide diuretic, which may be a basis for individualization of antihypertensive drug therapy and identification of new drug targets.
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| 38. |
- von Beckerath, Mathias P., 1966-, et al.
(författare)
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Outcome of primary treatment of early laryngeal malignancies using photodynamic therapy
- 2014
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 134:8, s. 852-858
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion: Photodynamic therapy (PDT) is a viable and safe option for early laryngeal cancer that would be less suitably treated with radiation or trans-oral laser surgery (TLS). The cure rates with PDT appear to be comparable to those of conventional therapy, and the voice outcomes are also comparable. In the case of many sarcomas, PDT appears to be an organ- and function-sparing therapy, although it is more costly than other treatments.Objectives: The aim of this study was to show the results of PDT when it is used as a primary treatment of early laryngeal cancer. Methods: We studied the results of PDT when used as a primary treatment. We looked at survival, effect on tumor, side effects, voice, and costs.Results: The follow-up period was a median of 59 months. Nine of 10 patients were cured of their laryngeal cancer. PDT alone cured seven patients. All four of the sarcomas were cured using temoporfin. Two of three tumors that involved the anterior commissure were cured using only interstitial illumination with PDT. No serious side effects were noted. The patient's voices were improved after treatment in 5 of 10 cases, and none had a worsened voice.
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