| 1. |
- Hossein Abbasi, Mohammad, et al.
(author)
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Haunted by shadows of the future : ARTEFACTS
- 2014
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Other publication (pop. science, debate, etc.)abstract
- Haunted by Shadows of the Future: ARTEFACTS identifierar föremål från slutet av1960-talet till slutet av 1970-talet som har ett personligt eller familjärt samband medmänniskorna och samhället under denna tid, och som innefattar en särskild känslaav tillhörighet, en önskan att vara en del av det moderna svenska samhälle som togform vid den tiden. Resultatet av detta kollektiva sökande är en samling artefakter,företeelser och föremål i hemmet, sammanflätade med rika personliga berättelser ochupptäckter. Dessa inbegriper en försäkringsförsäljares portfölj, en rullbandspelaresom fångade ett populärt radioprogram med en pratshow, en inspelning med enlandsflyktig somalisk författare, tidiga exemplar av plastleksaker, diabilder frånsemestrar, vykortssamlingar och super 8 filmer, textiltryck med popmönster ochmönster för klädesplagg, lokala grönplanteringar, en affärskedjas lansering av ettanti-varumärke, den revolutionerande ”du”-reformen, och andra samtida referenser,som ett svenskt kvinnomanifest och en populär oljevärmare från Iran. Stadsmuseetsvisningslägenhet i Tensta på Kämpingebacken 13, tjänar här som en tidskapsel somöppnar en hel värld bakom dessa YTTERST vardagliga föremål.
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| 2. |
- Ameur, Adam, et al.
(author)
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Genetic Adaptation of Fatty-Acid Metabolism : A Human-Specific Haplotype Increasing the Biosynthesis of Long-Chain Omega-3 and Omega-6 Fatty Acids
- 2012
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:5, s. 809-820
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Journal article (peer-reviewed)abstract
- Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease.
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| 3. |
- Apweiler, Rolf, et al.
(author)
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Approaching clinical proteomics : current state and future fields of application in cellular proteomics
- 2009
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In: Cytometry. Part A : the journal of the International Society for Analytical Cytology. - : Wiley. - 1552-4922. ; 75A:10, s. 816-832
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Research review (peer-reviewed)abstract
- Recent developments in proteomics technology offer new opportunities for clinical applications in hospital or specialized laboratories including the identification of novel biomarkers, monitoring of disease, detecting adverse effects of drugs, and environmental hazards. Advanced spectrometry technologies and the development of new protein array formats have brought these analyses to a standard, which now has the potential to be used in clinical diagnostics. Besides standardization of methodologies and distribution of proteomic data into public databases, the nature of the human body fluid proteome with its high dynamic range in protein concentrations, its quantitation problems, and its extreme complexity present enormous challenges. Molecular cell biology (cytomics) with its link to proteomics is a new fast moving scientific field, which addresses functional cell analysis and bioinformatic approaches to search for novel cellular proteomic biomarkers or their release products into body fluids that provide better insight into the enormous biocomplexity of disease processes and are suitable for patient stratification, therapeutic monitoring, and prediction of prognosis. Experience from studies of in vitro diagnostics and especially in clinical chemistry showed that the majority of errors occurs in the preanalytical phase and the setup of the diagnostic strategy. This is also true for clinical proteomics where similar preanalytical variables such as inter- and intra-assay variability due to biological variations or proteolytical activities in the sample will most likely also influence the results of proteomics studies. However, before complex proteomic analysis can be introduced at a broader level into the clinic, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement, and data analysis is another issue which has to be improved. In this report, we discuss the recent advances and applications that fulfill the criteria for clinical proteomics with the focus on cellular proteomics (cytoproteomics) as related to preanalytical and analytical standardization and to quality control measures required for effective implementation of these technologies and analytes into routine laboratory testing to generate novel actionable health information. It will then be crucial to design and carry out clinical studies that can eventually identify novel clinical diagnostic strategies based on these techniques and validate their impact on clinical decision making.
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| 4. |
- Apweiler, Rolf, et al.
(author)
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Approaching clinical proteomics : current state and future fields of application in fluid proteomics
- 2009
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In: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 47:6, s. 724-744
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Research review (peer-reviewed)abstract
- The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
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| 5. |
- Demir, Selvan, et al.
(author)
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Pursuing the excision of carbon-centred hexanuclear scandium clusters {CSc6} from solid {CSc6}I12Sc
- 2022
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In: Australian journal of chemistry (Print). - : CSIRO Publishing. - 0004-9425 .- 1445-0038. ; 75:9, s. 523-531
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Journal article (peer-reviewed)abstract
- A multi-gram synthetic route to black solid {CSc6}I12Sc (1) was developed which comprises the reaction of scandium triiodide, ScI3, with graphite and scandium metal at 850°C. Compound 1 dissolved in N,N-dimethylacetamide (DMA) to form a red solution. Results derived from 45Sc NMR and EPR spectroscopy indicated that a scandium cluster species exists in this solution along with a complex cation [Sc(DMA)6]3+. From these solutions crystals of [Sc(DMA)6]I3 (2) and a red oily product was isolated. Compound 2 was also prepared independently by dissolving ScI3 in DMA and two polymorphs, orthorhombic 2O and monoclinic 2M were crystallised. {CSc6}I12Sc (1) also dissolved in THF yielding a red solution which contains [ScI6]3− and a scandium cluster species, as analysed by 45Sc NMR and EPR spectroscopy.
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| 6. |
- Demirkan, Ayse, et al.
(author)
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Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations
- 2012
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:2, s. e1002490-
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Journal article (peer-reviewed)abstract
- Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88 x 10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10 x 10(-57)). After a correction for multiple comparisons (P-value, 2.2 x 10(-9)), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits.
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| 7. |
- Demirkan, Ayse, et al.
(author)
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Plasma phosphatidylcholine and sphingomyelin concentrations are associated with depression and anxiety symptoms in a Dutch family-based lipidomics study
- 2013
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In: Journal of Psychiatric Research. - : Elsevier BV. - 0022-3956 .- 1879-1379. ; 47:3, s. 357-362
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Journal article (peer-reviewed)abstract
- The central nervous system has the second highest concentration of lipids after adipose tissue. Alterations in neural membrane phospho- and sphingolipid composition can influence crucial intra- and intercellular signalling and alter the membrane's properties. Recently, the polyunsaturated fatty acids (PUFA) hypothesis for depression suggests that phospho- and sphingolipid metabolism includes potential pathways for the disease. In 742 people from a Dutch family-based study, we assessed the relationships between 148 different plasma phospho- and sphingolipid species and depression/anxiety symptoms as measured by the Hospital Anxiety and Depression Scales (HADS-A and HADS-D) and the Centre for Epidemiological Studies Depression Scale (CES-D). We observed significant differences in plasma sphingomyelins (SPM), particularly the SPM 23:1/SPM 16:0 ratio, which was inversely correlated with depressive symptom scores. We observed a similar trend for plasma phosphatidylcholines (PC), particularly the molar proportion of PC O 36:4 and its ratio to ceramide CER 20:0. Absolute levels of PC O 36:4 were also associated with depression symptoms in an independent replication. To our knowledge this is the first study on depressive symptoms that focuses on specific phospho- and sphingolipid molecules in plasma rather than total PUFA concentrations. The findings of this lipidomic study suggests that plasma sphingomyelins and ether phospholipids should be further studied for their potential as biomarkers and for a better understanding of the underlying mechanisms of this systemic disease.
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| 8. |
- Hicks, Andrew A., et al.
(author)
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Genetic determinants of circulating sphingolipid concentrations in European populations
- 2009
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:10, s. e1000672-
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Journal article (peer-reviewed)abstract
- Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic β-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08×10−66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1–3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10−4 or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases.
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| 9. |
- Igl, Wilmar, et al.
(author)
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Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population
- 2013
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In: International Journal of Circumpolar Health. - : Informa UK Limited. - 1239-9736 .- 2242-3982. ; 72, s. 421-427
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Journal article (peer-reviewed)abstract
- Background. The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. Objective. To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. Study design. We compared a group with traditional lifestyle (TLS) based on reindeer herding (TLS group) with those from the same area with a non-traditional lifestyle (NTLS) typical of more industrialized regions of Sweden (NTLS group). The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs) and the serum blood level of a number of lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), glycerophospholipids and sphingolipids]. Results. The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (>= 240 mg/dl), as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. Conclusions. The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS) group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.
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| 10. |
- Igl, Wilmar, et al.
(author)
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Glycomics meets lipidomics-associations of N-glycans with classical lipids, glycerophospholipids, and sphingolipids in three European populations
- 2011
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In: Molecular BioSystems. - : Royal Society of Chemistry (RSC). - 1742-206X .- 1742-2051. ; 7:6, s. 1852-1862
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Journal article (peer-reviewed)abstract
- Recently, high-throughput technologies have been made available which allow the measurement of a broad spectrum of glycomics and lipidomics parameters in many samples. The aim of this study was to apply these methods and investigate associations between 46 glycan and 183 lipid traits measured in blood of 2041 Europeans from three different local populations (Croatia - VIS cohort; Sweden - NSPHS cohort; Great Britain - ORCADES cohort). N-glycans have been analyzed with High Performance Liquid Chromatography (HPLC) and lipids with Electrospray Ionization Tandem Mass Spectrometry (ESI-MS/MS) covering sterol lipids, glycerolipids, glycerophospholipids and sphingolipids in eight subclasses. Overall, 8418 associations were calculated using linear mixed effect models adjusted for pedigree, sex, age and multiple testing. We found 330 significant correlations in VIS. Pearson's correlation coefficient r ranged from -0.27 to 0.34 with corresponding p-values between 1.45 x 10(-19) and 4.83 x 10(-6), indicating statistical significance. A total of 71 correlations in VIS could be replicated in NSPHS (r = [-0.19; 0.35], p = [4.16 x 10(-18); 9.38 x 10(-5)]) and 31 correlations in VIS were also found in ORCADES (r = [-0.20; 0.24], p = [2.69 x 10(-10); 7.55 x 10(-5)]). However, in total only 10 correlations between a subset of triantennary glycans and unsaturated phosphatidylcholine, saturated ceramide, and sphingomyelin lipids in VIS (r = [0.18; 0.34], p = [2.98 x 10(-21); 1.69 x 10(-06)]) could be replicated in both NSPHS and ORCADES. In summary, the results show strong and consistent associations between certain glycans and lipids in all populations, but also population-specific correlations which may be caused by environmental and genetic differences. These associations point towards potential interactive metabolic pathways.
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