| 1. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 2. |
- Jakobsdottir, Johanna, et al.
(författare)
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Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease
- 2016
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.
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| 3. |
- Maróti, Zoltán, et al.
(författare)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Tidskriftsartikel (refereegranskat)abstract
- Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this “immigrant core” of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common “proto-Ugric” gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring “native European” ancestry.
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| 4. |
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| 5. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 6. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 7. |
- Alfonso, Fernando, et al.
(författare)
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Authorship : from credit to accountability. Reflections from the Editors' Network.
- 2019
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Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 108:7, s. 723-729
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Tidskriftsartikel (refereegranskat)abstract
- The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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| 8. |
- Alfonso, Fernando, et al.
(författare)
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Authorship : From credit to accountability - Reflections from the Editors' network.
- 2019
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Ingår i: Archivos de cardiologia de Mexico. - 1665-1731. ; 89:1, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new -(fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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| 9. |
- Alfonso, Fernando, et al.
(författare)
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Authorship : From credit to accountability. Reflections from the Editors' Network.
- 2019
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Ingår i: Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. - : Elsevier BV. - 2174-2030. ; 38:7, s. 519-525
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Tidskriftsartikel (refereegranskat)abstract
- The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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| 10. |
- Alfonso, Fernando, et al.
(författare)
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Authorship : From credit to accountability - Reflections from the Editors' network.
- 2019
-
Ingår i: Archivos de cardiologia de Mexico. - 1665-1731. ; 89:2, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- The Editors' Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new -(fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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| 11. |
- Alfonso, Fernando, et al.
(författare)
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Authorship : from credit to accountability. Reflections from the Editors' Network.
- 2019
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Ingår i: Basic Research in Cardiology. - : Springer Science and Business Media LLC. - 0300-8428 .- 1435-1803. ; 114:3
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Tidskriftsartikel (refereegranskat)abstract
- The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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| 12. |
- Alfonso, Fernando, et al.
(författare)
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Authorship : From Credit to Accountability Reflections From the Editors´ Network.
- 2019
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Ingår i: Anatolian journal of cardiology. - 2149-2263 .- 2149-2271. ; 21:5, s. 281-286
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Tidskriftsartikel (refereegranskat)abstract
- The Editors´ Network of the European Society of Cardiology (ESC) provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.
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| 13. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 14. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 15. |
- Finy, Peter, et al.
(författare)
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Exploring diversity within the genus Tulostoma (Basidiomycota, Agaricales) in the Pannonian sandy steppe : four fascinating novel species from Hungary
- 2023
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; :100, s. 153-170
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Tidskriftsartikel (refereegranskat)abstract
- Steppe vegetation on sandy soil in Hungary has recently been revealed as one of the hot spots in Europe for the stalked puffballs (genus Tulostoma). In the framework of the taxonomic revision of gasteroid fungi in Hungary, four Tulostoma species are described here as new to science: T. dunense, T. hungaricum, T. sacchariolens and T. shaihuludii. The study is based on detailed macro-and micromorphological investigations (including light and scanning electron microscopy), as well as a three-locus phylogeny of nrDNA ITS, nrDNA LSU and tef1-alpha sequences. The ITS and LSU sequences generated from the type specimen of T. cretaceum are provided and this resolved partly the taxonomy of the difficult species complex of T. aff. cretaceum.
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| 16. |
- Fretts, Amanda M., et al.
(författare)
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Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores : a meta-analysis of 50,345 Caucasians
- 2015
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 102:5, s. 1266-1278
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined l) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-1n-pmon (95% CI: 0.035, 0.063-1n-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. Conclusion: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms.
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| 17. |
- Kraja, Aldi T., et al.
(författare)
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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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| 18. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 19. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 20. |
- Matthews, Bethany E., et al.
(författare)
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Micro- and Nanoscale Surface Analysis of Late Iron Age Glass from Broborg, a Vitrified Swedish Hillfort
- 2023
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Ingår i: Microscopy and Microanalysis. - : Oxford University Press. - 1431-9276 .- 1435-8115. ; 29:1, s. 50-68
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Tidskriftsartikel (refereegranskat)abstract
- Archaeological glasses with prolonged exposure to biogeochemical processes in the environment can be used to understand glass alteration, which is important for the safe disposal of vitrified nuclear waste. Samples of mafic and felsic glasses with different chemistries, formed from melting amphibolitic and granitoid rocks, were obtained from Broborg, a Swedish Iron Age hillfort. Glasses were excavated from the top of the hillfort wall and from the wall interior. A detailed microscopic, spectroscopic, and diffraction study of surficial textures and chemistries were conducted on these glasses. Felsic glass chemistry was uniform, with a smooth surface showing limited chemical alteration (<150 nm), irrespective of the position in the wall. Mafic glass was heterogeneous, with pyroxene, spinel, feldspar, and quartz crystals in the glassy matrix. Mafic glass surfaces in contact with topsoil were rougher than those within the wall and had carbon-rich material consistent with microbial colonization. Limited evidence for chemical or physical alteration of mafic glass was found; the thin melt film that coated all exposed surfaces remained intact, despite exposure to hydraulically unsaturated conditions, topsoil, and associated microbiome for over 1,500 years. This supports the assumption that aluminosilicate nuclear waste glasses will have a high chemical durability in near-surface disposal facilities.
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| 21. |
- Perdikari, A., et al.
(författare)
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BATLAS: Deconvoluting Brown Adipose Tissue
- 2018
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- Recruitment and activation of thermogenic adipocytes have received increasing attention as a strategy to improve systemic metabolic control. The analysis of brown and brite adipocytes is complicated by the complexity of adipose tissue biopsies. Here, we provide an in-depth analysis of pure brown, brite, and white adipocyte transcriptomes. By combining mouse and human transcriptome data, we identify a gene signature that can classify brown and white adipocytes in mice and men. Using a machine-learning-based cell deconvolution approach, we develop an algorithm proficient in calculating the brown adipocyte content in complex human and mouse biopsies. Applying this algorithm, we can show in a human weight loss study that brown adipose tissue (BAT) content is associated with energy expenditure and the propensity to lose weight. This online available tool can be used for in-depth characterization of complex adipose tissue samples and may support the development of therapeutic strategies to increase energy expenditure in humans.
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| 22. |
- Popescu, Bogdan A, et al.
(författare)
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European Association of Echocardiography recommendations for training, competence, and quality improvement in echocardiography
- 2009
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Ingår i: European Journal of Echocardiography. - : Oxford University Press (OUP). - 1525-2167 .- 1532-2114. ; 10:8, s. 893-905
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Tidskriftsartikel (refereegranskat)abstract
- The main mission statement of the European Association of Echocardiography (EAE) is 'to promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular ultrasound in Europe'. As competence and quality control issues are increasingly recognized by patients, physicians, and payers, the EAE has established recommendations for training, competence, and quality improvement in echocardiography. The purpose of this document is to provide the requirements for training and competence in echocardiography, to outline the principles of quality measurement, and to recommend a set of measures for improvement, with the ultimate goal of raising the standards of echocardiographic practice in Europe.
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| 23. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 24. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 25. |
- Weaver, Jamie L., et al.
(författare)
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Pre‐Viking Swedish Hillfort Glass : A Prospective Long‐Term Alteration Analogue for Vitrified Nuclear Waste
- 2018
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Ingår i: The International Journal of Applied Glass Science (IJAGS). - : John Wiley & Sons. - 2041-1294 .- 2041-1286. ; 9:4, s. 540-554
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Tidskriftsartikel (refereegranskat)abstract
- Models for long‐term glass alteration are required to satisfy performance predictions of vitrified nuclear waste in various disposal scenarios. Durability parameters are usually extracted from short‐term laboratory tests, and sometimes checked with long‐term natural experiments on glasses, termed analogues. In this paper, a unique potential ancient glass analogue from Sweden is discussed. The hillfort glass found at Broborg represents a unique case study as a vitrified waste glass analogue to compare to Low Activity Waste glass to be emplaced in near surface conditions at Hanford (Washington State). Glasses at Broborg have similar and dissimilar compositions to LAW glass, allowing the testing of long‐term alteration of different glass chemistries. Additionally, the environmental history of the site is reasonably well documented. Initial investigations on previously collected samples established methodologies for handling and characterizing these artifacts by laboratory methods while preserving their alteration layers and cultural context. Evidence of possible biologically influenced glass alteration, and differential alteration in the two types of glass found at the Broborg site is presented.
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