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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- 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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| 4. |
- 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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| 5. |
- Hait, A. S., et al.
(författare)
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Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans
- 2020
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Ingår i: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:54
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Tidskriftsartikel (refereegranskat)abstract
- Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret's meningitis that each carry a rare monoallelic variant in the autophagy proteins ATG4A or LC3B2. HSV2-activated autophagy was abrogated in patient primary fibroblasts, which also exhibited significantly increased viral replication and enhanced cell death. HSV2 antigen was captured in autophagosomes of infected cells, and genetic inhibition of autophagy by disruption of autophagy genes, including ATG4A and LC3B2, led to enhanced viral replication and cell death in primary fibroblasts and a neuroblastoma cell line. Activation of autophagy by HSV2 was sensitive to ultraviolet (UV) irradiation of the virus and inhibited in the presence of acyclovir, but HSV2-induced autophagy was independent of the DNA-activated STING pathway. Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.
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| 6. |
- van As, Dirk, et al.
(författare)
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Darkening of the Greenland ice sheet due to the melt-albedo feedback observed at PROMICE weather stations
- 2013
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Ingår i: Geological Survey of Denmark and Greenland Bulletin. - 1811-4598 .- 1604-8156. ; 28, s. 69-72
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Tidskriftsartikel (refereegranskat)abstract
- The Greenland ice sheet is losing mass (Barletta et al. 2012) and at least half of this loss is caused by an increase in surface melt (e.g. Tedesco et al. 2013). The other part is caused by increased dynamic mass loss, as marine-terminating glaciers lose resistive stresses (Nick et al. 2009) due to both retreat and meltwater lubrication at the bed (Sasgen et al. 2012).In 2007, the Programme for Monitoring of the Greenland Ice Sheet (PROMICE) was initiated with the aim of gaining an insight into the causes of the ice-mass budget changes based on quantitative observations. This is primarily done by assessing how much mass is gained as snow accumulation on the surface versus how much is lost by calving and surface ablation (Ahlstrøm et al. 2008). PROMICE monitors the surface mass balance by means of automatic weather stations (AWSs) designed to quantify accumulation and ablation, as well as the specific energy sources contributing to ablation. These observations are vital to interpreting the physical mechanisms for ice-sheet response to climate change and for the calibration and validation of both satellite observations and climate models.In the wake of several record-breaking warm summers – increasing surface melt rate and extent (Nghiem et al. 2012) – interest in Greenland’s surface mass balance has increased (Tedesco et al. 2013). Observations of net ablation at PROMICE stations provided in situ confirmation of extreme massloss events in 2010 (Fausto et al. 2012) and 2012, primarily documented by other workers through satellite data. In this paper, we present atmospheric temperatures and surface solar reflectivity (known as albedo) of the Greenland ice sheet in the PROMICE period. Albedo modulates the absorption of solar radiation, which is the primary source of melt energy. It is reported to be decreasing in Greenland in recent years (Box et al. 2012), causing the monitoring of albedo variability to be increasingly important. Air temperatures, besides being strongly correlated to surface melt rates, affect surface albedo by controlling the rate of snow-grain metamorphism and the fraction of summer precipitation falling as rain versus snow. To elucidate the so-called melt-albedo feedback, whereby increased melt darkens the ice sheet and further enhances melt, the relationship between albedo and air temperature, observed at PROMICE stations, is examined in this study.
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| 7. |
- van As, Dirk, et al.
(författare)
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Katabatic winds and piteraq storms : observations from the Greenland ice sheet
- 2014
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Ingår i: Geological Survey of Denmark and Greenland Bulletin. - 1811-4598 .- 1604-8156. ; 31, s. 83-86
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Tidskriftsartikel (refereegranskat)abstract
- In 2007 the Programme for Monitoring the Greenland Ice Sheet (PROMICE) was initiated to observe and gain insight into the mass budget of Greenland ice masses. By means of in situ observations and remote sensing, PROMICE assesses how much mass is gained as snow accumulation on the surface versus how much is lost by iceberg calving and surface ablation (Ahlstrøm et al. 2008). A key element of PROMICE is a network of automatic weather stations (AWSs) designed to quantify components of the surface mass balance, including the energy exchanges contributing to surface ablation (Van As et al. 2013).The use of these AWS observations is not limited to studies of ice-sheet mass balance. PROMICE contributes to CryoNet (www.globalcryospherewatch.org/cryonet), the core network of surface measurement sites of the World Meteorological Organization (WMO) Global Cryosphere Watch. By real-time delivery through WMO, PROMICE observations contribute to improve both operational forecasting and climate analysis in the data-sparse Arctic. The Greenlandic population, highly dependent on accurate forecasting of weather conditions, benefits directly from these real-time observations. For instance, extreme surface wind speeds are a high-risk element in Greenland. The third-highest wind speed observed at the surface of the Earth (93 m/s or 333 km/h), was recorded in a 8–9 March 1972 storm at Thule in North-West Greenland (Stansfield 1972).In this paper, we discuss the extent to which the Greenland ice sheet generates its own near-surface wind field. We use PROMICE data to gain insight into the interaction between air temperature, radiation and gravity-driven katabatic winds. We focus on a particularly powerful spring storm in 2013 that contributed to a fatality on an ice-sheet ski traverse attempt (Linden 2013).
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| 8. |
- Burisch, Johan, et al.
(författare)
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Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort : an ECCO-EpiCom Study
- 2015
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Ingår i: Inflammatory Bowel Diseases. - 1078-0998 .- 1536-4844. ; 21:1, s. 121-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe.METHODS: The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (&OV0556;) using the Danish Health Costs Register.RESULTS: One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was &OV0556;5,408,174 (investigations: &OV0556;2,042,990 [38%], surgery: &OV0556;1,427,648 [26%], biologicals: &OV0556;781,089 [14%], and standard treatment: &OV0556;1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations &OV0556;1803 (&OV0556;2160) (P = 0.44), surgery &OV0556;11,489 (&OV0556;13,973) (P = 0.14), standard treatment &OV0556;1027 (&OV0556;824) (P = 0.51), and biologicals &OV0556;7376 (&OV0556;8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations &OV0556;1189 (&OV0556;1518) (P < 0.01), surgery &OV0556;18,414 (&OV0556;12,395) (P = 0.18), standard treatment &OV0556;896 (&OV0556;798) (P < 0.05), and biologicals &OV0556;5681 (&OV0556;72) (P = 0.51).CONCLUSIONS: In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.
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| 9. |
- Nilsson, Mattias, et al.
(författare)
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Gaussian Mixture Model based Mutual Information Estimation between Frequency Bands in Speech
- 2002
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Ingår i: 2002 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS I-IV, PROCEEDINGS. - 0780374029 ; , s. 525-528
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Konferensbidrag (refereegranskat)abstract
- In this paper, we investigate the dependency between the spectral envelopes of speech in disjoint frequency bands, one covering the telephone bandwidth from 0.3 kHz to 3.4 kHz and one covering the frequencies from 3.7 kHz to 8 kHz. The spectral envelopes are jointly modeled with a Gaussian mixture model based on mel-frequency cepstral coefficients and the log-energy-ratio of the disjoint frequency bands. Using this model, we quantify the dependency between bands through their mutual information and the perceived entropy of the high frequency band. Our results indicate that the mutual information is only a small fraction of the perceived entropy of the high band. This suggests that speech bandwidth extension should not rely only on mutual information between narrow- and high-band spectra. Rather, such methods need to make use of perceptual properties to ensure that the extended signal sounds pleasant.
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| 10. |
- Orrem, Hilde L, et al.
(författare)
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Acute heart failure following myocardial infarction : complement activation correlates with the severity of heart failure in patients developing cardiogenic shock.
- 2018
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 5:3, s. 292-301
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Heart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction.METHODS AND RESULTS: The LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention-treated ST-elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow-up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non-shock group (n = 52). Controls (n = 44) were age-matched and sex-matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b-9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non-shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b-9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b-9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM-1 and sVCAM-1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b-9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively).CONCLUSIONS: Complement activation discriminated cardiogenic shock from non-shock in acute ST-elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.
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