| 1. |
- Allentoft, Morten E., et al.
(författare)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 2. |
- Allentoft, Morten E., et al.
(författare)
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Population genomics of post-glacial western Eurasia
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 3. |
- Petersen, Anders Ø., et al.
(författare)
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Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.
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| 4. |
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| 5. |
- Banasik, Karina, et al.
(författare)
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The FOXO3A rs2802292 G-Allele Associates with Improved Peripheral and Hepatic Insulin Sensitivity and Increased Skeletal Muscle-FOXO3A mRNA Expression in Twins.
- 2011
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96, s. 119-124
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The minor G allele of FOXO3A rs2802292 has been associated with longevity. We aimed to investigate whether a phenotype related to healthy metabolic aging could be identified in individuals carrying the longevity-associated FOXO3A rs2802292 G allele. Research Design and Methods: rs2802292 was genotyped in a phenotypically well-characterized population of young and elderly twins (n = 190) and in the population-based Inter99 cohort (n = 5768). All participants underwent oral glucose tolerance tests, and the twin population was additionally examined with an iv glucose tolerance test and a hyperinsulinemic, euglycemic clamp. Basal and insulin-stimulated FOXO3A mRNA expression was assessed in skeletal muscle biopsies from the twin population. Results: In the twin sample, carriers of the minor G allele of rs2802292 showed reduced fasting plasma insulin [per allele effect (β) = -13% (-24; -1) (95% confidence interval), P = 0.03] and lower incremental area under the curve 0-120 min for insulin after an oral glucose load [β = -14% (-23; -), P = 0.005]. The G allele was associated with increased peripheral insulin action [glucose disposal rate clamp, β = 0.85 mg·kgfat-free mass(-1) · min(-1) (0.049; 1.64), P = 0.04] and lower hepatic insulin resistance index [β = -13% (-25; -1), P = 0.03]. Furthermore, carriers of the G allele had increased basal FOXO3A mRNA expression in skeletal muscle compared with T-allele carriers [β = 16% (0; 33), P = 0.047]. In the Inter99 sample, we found an association with reduced incremental area under the curve 0-120 min for insulin after an oral glucose load [β = -3% (-5; -0.07), P = 0.04], but this association was not significant after adjustment for body mass index. Conclusion: Our data indicate that the minor G allele of FOXO3A rs2802292 is associated with enhanced peripheral and hepatic insulin sensitivity in our small twin cohort, which may be mediated through increased FOXO3A mRNA expression, although no major metabolic impact of rs2802292 was found in the large Inter99 cohort.
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| 6. |
- Gammelgaard Wallstroem, Iben, et al.
(författare)
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A Systematic review of individual Placement and Support, Employment, and Personal and Clinical recovery
- 2021
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Ingår i: Psychiatric Services. - : American Psychiatric Association Publishing. - 1075-2730 .- 1557-9700. ; 72:9, s. 1040-1047
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Forskningsöversikt (refereegranskat)abstract
- Objective:The objective of this review was to assess associations between Individual Placement and Support (IPS), employment, and personal and clinical recovery among persons with severe mental illness at 18-month follow-up.Methods:A systematic literature search identified randomized controlled trials (RCTs) comparing IPS with services as usual. Outcomes were self-esteem, empowerment, quality of life, symptoms of depression, negative or psychotic symptoms, anxiety, and level of functioning. A total of six RCTs reported data suitable for meta-analyses, and pooled original data from five studies were also analyzed.Results:Meta-analyses and analyses of pooled original data indicated that receipt of the IPS intervention alone did not improve any of the recovery outcomes. Participants who worked during the study period, whether or not they were IPS participants, experienced improved negative symptoms, compared with those who did not work (standardized mean difference [SMD]=−0.41, 95% confidence interval [CI]=−0.56, –0.26). For participants who worked, whether or not they were IPS participants, improvements were also found in level of functioning and quality of life (SMD=0.59, 95% CI=0.42, 0.77 and SMD=0.34, 95% CI=0.14, 0.54, respectively).Conclusions:Employment was associated with improvements in negative symptoms, level of functioning, and quality of life.
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| 7. |
- Grunnet, Louise G., et al.
(författare)
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Regulation and Function of FTO mRNA Expression in Human Skeletal Muscle and Subcutaneous Adipose Tissue
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:10, s. 2402-2408
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Common variants in FTO (the fat mass- and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and nongenetic regulation of FTO mRNA in skeletal muscle and adipose tissue and their influence on in vivo glucose and fat metabolism. RESEARCH DESIGN AND METHODS-The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years) and elderly (58-66 years) nondiabetic twins examined by a hyperinsulinemic-euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n = 226) and skeletal muscle biopsies (n = 158). RESULTS-Heritability of FTO expression in both tissues was low, and FTO expression was not influenced by FTO rs9939609 genotype. FTO mRNA expression in skeletal muscle was regulated by age and sex, whereas age and BMI were predictors of adipose tissue FTO mRNA expression. FTO mRNA expression in adipose tissue was associated with an atherogenic lipid profile. In skeletal muscle, FTO mRNA expression was negatively associated to fat and positively to glucose oxidation rates as well as positively correlated with expression of genes involved in oxidative phosphorylation including PGC1 alpha. CONCLUSIONS-The heritability of FTO expression in adipose tissue and skeletal muscle is low and not influenced by obesity-associated FTO genotype. The age-dependent decline in FTO expression is associated with peripheral defects of glucose and fat metabolism. Diabetes 58:2402-2408, 2009
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| 8. |
- Hellström, Lone, et al.
(författare)
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Vocational Outcomes of the Individual Placement and Support Model in Subgroups of Diagnoses, Substance Abuse, and Forensic Conditions : A Systematic Review and Analysis of Pooled Original Data
- 2021
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Ingår i: Journal of Occupational Rehabilitation. - : Springer Science and Business Media LLC. - 1053-0487 .- 1573-3688. ; 31:4, s. 699-710
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Forskningsöversikt (refereegranskat)abstract
- Purpose: To investigate the effect of Individual Placement and Support (IPS) according to diagnoses of schizophrenia, bipolar disorder, major depression, substance use disorders, or forensic psychiatric conditions. Methods: A systematic search of the literature was conducted in June 2017 and repeated in December 2020. The systematic review included 13 studies. Analyses of pooled original data were based on the six studies providing data (n = 1594). No studies on forensic psychiatric conditions were eligible. Hours and weeks worked were analyzed using linear regression. Employment, and time to employment was analyzed using logistic regression, and cox-regression, respectively. Results: The effects on hours and weeks in employment after 18 months were comparable for participants with schizophrenia, and bipolar disorder but only statistically significant for participants with schizophrenia compared to services as usual (SAU) (EMD 109.1 h (95% CI 60.5–157.7), 6.1 weeks (95% CI 3.9–8.4)). The effect was also significant for participants with any drug use disorder (121.2 h (95% CI 23.6–218.7), 6.8 weeks (95% CI 1.8–11.8)). Participants with schizophrenia, bipolar disorder, and any drug use disorder had higher odds of being competitively employed (OR 2.1 (95% CI 1.6–2.7); 2.4 (95% CI 1.3–4.4); 3.0 (95% CI 1.5–5.8)) and returned to work faster than SAU (HR 2.1 (95% CI 1.6–2.6); 1.8 (95% CI 1.1–3.1); 3.0 (95% CI 1.6–5.7)). No statistically significant effects were found regarding depression. Conclusions: IPS was effective regarding schizophrenia, bipolar disorder, and substance use disorder; however, the effect on hours, and weeks worked was not statistically significant regarding bipolar disorder. For people with depression the impact of IPS remains inconclusive. Non-significant results may be due to lack of power. Trial Registration: PROSPERO protocol nr. CRD42017060524.
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| 9. |
- Jensen, Vivi F.H., et al.
(författare)
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Inner histopathologic changes and disproportionate zone volumes in foetal growth plates following gestational hypoglycaemia in rats
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Maternal hypoglycaemia throughout gestation until gestation day (GD)20 delays foetal growth and skeletal development. While partially prevented by return to normoglycaemia after completed organogenesis (GD17), underlying mechanisms are not fully understood. Here, we investigated the pathogenesis of these changes and significance of maternal hypoglycaemia extending beyond organogenesis in non-diabetic rats. Pregnant rats received insulin-infusion until GD20 or GD17, with sacrifice on GD20. Hypoglycaemia throughout gestation increased maternal corticosterone levels, which correlated with foetal levels. Growth plates displayed central histopathologic changes comprising disrupted cellular organisation, hypertrophic chondrocytes, and decreased cellular density; expression of pro-angiogenic factors, HIF-1α and VEGF-A increased in surrounding areas. Disproportionately decreased growth plate zone volumes and lower expression of the structural protein MATN-3 were seen, while bone ossification parameters were normal. Ending maternal/foetal hypoglycaemia on GD17 reduced incidence and severity of histopathologic changes and with normal growth plate volume. Compromised foetal skeletal development following maternal hypoglycaemia throughout gestation is hypothesised to result from corticosterone-induced hypoxia in growth plates, where hypoxia disrupts chondrocyte maturation and growth plate structure and volume, decreasing long bone growth. Maternal/foetal hypoglycaemia lasting only until GD17 attenuated these changes, suggesting a pivotal role of glucose in growth plate development.
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| 10. |
- Ladegaard-Pedersen, Pernille, et al.
(författare)
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Testing Late Bronze Age mobility in southern Sweden in the light of a new multi-proxy strontium isotope baseline of Scania
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The Bronze Age of Sweden’s southernmost region, Scania, is complex and intriguing. One could say that Scania represented in many ways a gateway for people, ideas and material culture connecting continental Europe with Sweden. Shedding light on the dynamics of human mobility in this region requires an in depth understanding of the local archaeological contexts across time. In this study, we present new archaeological human data from the Late Bronze Age Simris II site, located in an area of Scania showing a dynamic environment throughout the Late Bronze Age, thus likely involving various forms of mobility. Because the characterization of solid strontium isotope baselines is vital for delineating human mobility in prehistory using the strontium isotope methodology, we introduce the first environmentally based multi-proxy (surface water-, plant- and soil leachates) strontium isotope baselines for sub-regions of Scania. Our results show, that the highly complex and spatially scattered lithologies characterising Scania does not allow for a spatially meaningful, geology-based grouping of multi-proxy data that could be beneficial for provenance studies. Instead, we propose sub-regional baselines for areas that don’t necessarily fully correspond and reflect the immediate distribution of bedrock lithologies. Rather than working with a Scania-wide multi-proxy baseline, which we define as Sr/ Sr = 0.7133 ± 0.0059 (n = 102, 2σ), we propose sub-regional, multi-proxy baselines as follows: Area 1, farthest to the north, by Sr/ Sr = 0.7184 ± 0.0061 (n = 16, 2σ); Area 2, comprising the mid and western part of Scania, with Sr/ Sr = 0.7140 ± 0.0043 (n = 48, 2σ); Area 3–4, roughly corresponding to a NW-SE trending zone dominated by horst-graben tectonics across Scania, plus the carbonate dominated south western part of Scania with Sr/ Sr = 0.7110 ± 0.0030 (n = 39, 2σ). Our results also reflect that the complexity of the geology of Scania requires systematic, high density, statistically sound sampling of multiple proxies to adequately constrain the baseline ranges, particularly of those areas dominated by Precambrian lithologies. The averaging effect of biosphere Sr in surface water might be beneficial for the characterization of baselines in such terranes. Our sub-regional, area-specific baselines allow for a first comparison of different baseline construction strategies (single-proxy versus multi-proxy; Scania-wide versus sub-regional). From the Late Bronze Age Simris II site, we identified six individuals that could be analysed for Sr isotopes, to allow for an interpretation of their provenance using the newly established, environmental strontium isotope baselines. All but one signature agrees with the local baselines, including the Sr/ Sr value we measured for a young individual buried in a house urn, typically interpreted as evidence for long distance contacts. The results are somewhat unexpected and provides new aspects into the complexity of Scandinavian Bronze Age societies. 87 86 87 86 87 86 87 86 87 86
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