| 281. |
- Skoglund, Pontus, et al.
(författare)
-
Genomic Diversity and Admixture Differs for Stone-Age Scandinavian Foragers and Farmers
- 2014
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 344:6185, s. 747-750
-
Tidskriftsartikel (refereegranskat)abstract
- Prehistoric population structure associated with the transition to an agricultural lifestyle in Europe remains a contentious idea. Population-genomic data from 11 Scandinavian Stone Age human remains suggest that hunter-gatherers had lower genetic diversity than that of farmers. Despite their close geographical proximity, the genetic differentiation between the two Stone Age groups was greater than that observed among extant European populations. Additionally, the Scandinavian Neolithic farmers exhibited a greater degree of hunter-gatherer–related admixture than that of the Tyrolean Iceman, who also originated from a farming context. In contrast, Scandinavian hunter-gatherers displayed no significant evidence of introgression from farmers. Our findings suggest that Stone Age foraging groups were historically in low numbers, likely owing to oscillating living conditions or restricted carrying capacity, and that they were partially incorporated into expanding farming groups.
|
|
| 282. |
- Skoglund, Pontus, et al.
(författare)
-
Origins and Genetic Legacy of Neolithic Farmers and Hunter-Gatherers in Europe
- 2012
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 336:6080, s. 466-469
-
Tidskriftsartikel (refereegranskat)abstract
- The farming way of life originated in the Near East some 11,000 years ago and had reached most of the European continent 5000 years later. However, the impact of the agricultural revolution on demography and patterns of genomic variation in Europe remains unknown. We obtained 249 million base pairs of genomic DNA from similar to 5000-year-old remains of three hunter-gatherers and one farmer excavated in Scandinavia and find that the farmer is genetically most similar to extant southern Europeans, contrasting sharply to the hunter-gatherers, whose distinct genetic signature is most similar to that of extant northern Europeans. Our results suggest that migration from southern Europe catalyzed the spread of agriculture and that admixture in the wake of this expansion eventually shaped the genomic landscape of modern-day Europe.
|
|
| 283. |
- Smith, Ruben, et al.
(författare)
-
The α-synuclein PET tracer [18F] ACI-12589 distinguishes multiple system atrophy from other neurodegenerative diseases
- 2023
-
Ingår i: Nature Communications. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- A positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately the treatment of α-synuclein-related diseases. Here we show that the PET ligand, [18F]ACI-12589, displays good in vitro affinity and specificity for pathological α-synuclein in tissues from patients with different α-synuclein-related disorders including Parkinson’s disease (PD) and Multiple-System Atrophy (MSA) using autoradiography and radiobinding techniques. In the initial clinical evaluation we include 23 participants with α-synuclein related disorders, 11 with other neurodegenerative disorders and eight controls. In vivo [18F]ACI-12589 demonstrates clear binding in the cerebellar white matter and middle cerebellar peduncles of MSA patients, regions known to be highly affected by α-synuclein pathology, but shows limited binding in PD. The binding statistically separates MSA patients from healthy controls and subjects with other neurodegenerative disorders, including other synucleinopathies. Our results indicate that α-synuclein pathology in MSA can be identified using [18F]ACI-12589 PET imaging, potentially improving the diagnostic work-up of MSA and allowing for detection of drug target engagement in vivo of novel α-synuclein targeting therapies.
|
|
| 284. |
- Sommer, Stefan, et al.
(författare)
-
Major Bottom Water Ventilation Events Do Not Significantly Reduce Basin-Wide Benthic N and P Release in the Eastern Gotland Basin (Baltic Sea)
- 2017
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 4:18
-
Tidskriftsartikel (refereegranskat)abstract
- Redox-sensitive mobilization of nutrients from sediments strongly affects the eutrophic state of the central Baltic Sea; a region associated with the spread of hypoxia and almost permanently anoxic and sulfidic conditions in the deeper basins. Ventilation of these basins depends on renewal by inflow of water enriched in oxygen (O2) from the North Sea, occurring roughly once per decade. Benthic fluxes and water column distributions of dissolved inorganic nitrogen species, phosphate (PO43-), dissolved inorganic carbon (DIC), sulfide (HS-) and total oxygen uptake (TOU) were measured along a depth gradient in the Eastern Gotland Basin (EGB). Campaigns were conducted during euxinic conditions of the deep basin in Aug./Sept. 2013 and after two inflow events in July/Aug. 2015 and March 2016 when O2 concentrations in deep waters reached 60 µM. The intrusion of O2-rich North Sea water into the EGB led to an approximate 33 % and 10 % reduction of the seabed PO43- and ammonium (NH4+) release from deep basin sediments. Post-inflow, the deep basin sediment was rapidly colonized by HS- oxidizing bacteria tentatively assigned to the family Beggiatoaceae, and HS- release was completely suppressed. The presence of a hypoxic transition zone (HTZ) between 80 and 120 m water depth was confirmed not only for euxinic deep-water conditions during 2013 but also for post-inflow conditions. Because deep-water renewal did not ventilate the HTZ, where PO43- and NH4+ fluxes were highest, high seabed nutrient release there was relatively unchanged. Extrapolation of the in situ nutrient fluxes indicated that, overall, the reduction in PO43- and NH4+ release in response to deep-water renewal can be considered as minor, reducing the internal nutrient load by 2 and 12 % only, respectively. Infrequent inflow events thus have a limited capacity to sustainably reduce internal nutrient loading in the EGB and mitigate eutrophication.
|
|
| 285. |
- Stevens, Kristen N, et al.
(författare)
-
19p13.1 is a triple negative-specific breast cancer susceptibility locus
- 2012
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
-
Tidskriftsartikel (refereegranskat)abstract
- The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
|
|
| 286. |
- Stigebrandt, Anders, 1942, et al.
(författare)
-
A new Phosphorus Paradigm for the Baltic Proper
- 2014
-
Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 43:5, s. 634-643
-
Tidskriftsartikel (refereegranskat)abstract
- The external phosphorus (P) loading has been halved, but the P content in the water column and the area of anoxic bottoms in Baltic proper has increased during the last 30 years. This can be explained by a temporary internal source of dissolved inorganic phosphorus (DIP) that is turned on when the water above the bottom sediment becomes anoxic. A load-response model, explaining the evolution from 1980 to 2005, suggests that the average specific DIP flux from anoxic bottoms in the Baltic proper is about 2.3 g P m-2 year-1. This is commensurable with fluxes estimated in situ from anoxic bottoms in the open Baltic proper and from hydrographic data in the deep part of Bornholm Basin. Oxygenation of anoxic bottoms, natural or manmade, may quickly turn off the internal P source from anoxic bottoms. This new P-paradigm should have far-reaching implications for abatement of eutrophication in the Baltic proper.
|
|
| 287. |
- Stigebrandt, Anders, 1942, et al.
(författare)
-
An Experiment with Forced Oxygenation of the Deepwater of the Anoxic By Fjord, Western Sweden
- 2015
-
Ingår i: Ambio. - : Springer Netherlands. - 0044-7447 .- 1654-7209. ; 44:1, s. 42-54
-
Tidskriftsartikel (refereegranskat)abstract
- In a 2.5-year-long environmental engineering experiment in the By Fjord, surface water was pumped into the deepwater where the frequency of deepwater renewals increased by a factor of 10. During the experiment, the deepwater became long-term oxic, and nitrate became the dominating dissolved inorganic nitrogen component. The amount of phosphate in the water column decreased by a factor of 5 due to the increase in flushing and reduction in the leakage of phosphate from the sediments when the sediment surface became oxidized. Oxygenation of the sediments did not increase the leakage of toxic metals and organic pollutants. The bacterial community was the first to show changes after the oxygenation, with aerobic bacteria also thriving in the deepwater. The earlier azoic deepwater bottom sediments were colonized by animals. No structural difference between the phytoplankton communities in the By Fjord and the adjacent Havsten Fjord, with oxygenated deepwater, could be detected during the experiment.
|
|
| 288. |
- Stitziel, Nathan O., et al.
(författare)
-
Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
- 2016
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
|
|
| 289. |
- Stolk, Lisette, et al.
(författare)
-
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
-
Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
|
|
| 290. |
- Strand, Fredrik, et al.
(författare)
-
Longitudinal fluctuation in mammographic percent density differentiates between interval and screen-detected breast cancer
- 2016
-
Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
-
Tidskriftsartikel (refereegranskat)abstract
- Interval breast cancer (IC) has a more aggressive phenotype and higher mortality than screen-detected cancer (SDC). In this case-case study, we investigated whether the size of longitudinal fluctuations in mammographic percent density (PD fluctuation) was associated with the ratio of IC versus SDC among screened women with breast cancer. The primary study population consisted of 1,414 postmenopausal breast cancer cases, and the validation population of 1,241 cases. We calculated PD fluctuation as the quadratic mean of deviations between actual PD and the long-term trend estimated by a mixed effects model. In a logistic regression model we examined the association between PD fluctuation and IC versus SDC including adjustments for PD at last screening, age at diagnosis, BMI and hormone replacement therapy. All statistical tests were two-sided. There were 385 IC and 1,029 SDC in the primary study population, with PD fluctuations of 0.44 and 0.41 respectively (p = 0.0309). After adjustments, PD fluctuation was associated with an increased ratio of IC versus SDC, with an estimated per-standard deviation odds ratio of 1.17 (95% CI = 1.03-1.33), compared to 1.19 (95% CI = 1.04-1.38) in the validation population. In screened women with breast cancer, high fluctuation in mammographic percent density was associated with an increased ratio of IC versus SDC. Whether this is entirely related to a reduced mammographic detectability or to a biological phenotype promoting faster tumor growth remains to be elucidated.
|
|
