| 1. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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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. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 5. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 6. |
- Belda, E., et al.
(författare)
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Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism
- 2022
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:12
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. Design We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. Results Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. Conclusion Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.
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| 7. |
- Moksnes, Per-Olav, et al.
(författare)
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Fritidsbåtars påverkan på grunda kustekosystem i sverige
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sveriges natursköna kust med vidsträckta skärgårdar erbjuder fantastiska förhållanden för fritidsbåtliv. Idag finns uppskattningsvis mer än 700 000 fritidsbåtar i Sverige, vilket är en av de högsta siffrorna i världen sett till befolkningsmängden. Kustens vågskyddade skärgård ger också goda förutsättningar att förvara fritidsbåtar vid bryggor, och idag täcks stora områden av bryggor och småbåtshamnar. Det stora antalet båtar och bryggor kan ge betydande effekter på miljön, men kunskapen om fritidsbåtlivets sammanlagda påverkan på Sveriges kustmiljöer har hittills varit bristfällig. Havsmiljöinstitutets mål med denna rapport har varit att sammanställa kunskapsläget kring hur fritidsbåtar påverkar grunda kustekosystem i Sverige, samt bedöma omfattningen av denna påverkan och om utveckling är hållbar. Syftet med rapporten är att bidra till utvecklingen av en mer hållbar förvaltning av fritidsbåtlivet genom att sammanställa vetenskaplig kunskap inom detta område på ett lättillgängligt sätt. Sammanställningen visar att det finns ett starkt stöd i den vetenskapliga litteraturen för att fritidsbåtar ger upphov till många negativa effekter på kustmiljön. Med fritidsbåtslivet följer en rad olika fysiska strukturer och aktiviteter som var och en ger upphov till flera olika typer av miljöpåverkan. En ökad utbredning av småbåtshamnar, bryggor och muddrade områden medför förluster av viktiga bottenmiljöer och leder ofta till en långvarig försämring av miljöförhållanden lokalt. Muddrings- och dumpningsaktiviteter leder till ökad uppgrumling och spridning av sediment, näringsämnen och miljögifter över stora områden, vilket bland annat påverkar bottenvegetation, fiskar och musslor negativt. Båttrafik och ankring leder till uppgrumling och erosion av sediment samt till skador på bottenmiljön. Undervattensbuller från båtarnas motorer stör också fiskar och däggdjur. Vidare medför användning av fritidsbåtar betydande utsläpp av giftiga ämnen och föroreningar från båtbottenfärger och förbränningsmotorer. Drygt 60 % av alla bryggor och småbåtshamnar återfinns i grunda (<3 m), vågskyddade områden med mjukbottnar, trots att de endast utgör en fjärdedel av kustens totala grundområden. Dessa områden lämpar sig väl för båtförvaring, men är också en av kustens mest produktiva och värdefulla miljöer. Grunda mjukbottnar är en viktig miljö för olika kärlväxter och kransalger, som i sin tur utgör viktiga uppväxthabitat för många olika fiskarter och kräftdjur. Rapporten visar att dessa miljöer är extra känsliga för en majoritet av de störningar som fritidsbåtlivet ger upphov till. Sammantaget medför detta att fritidsbåtslivet i förhållande till sin omfattning genererar stora skador på miljöer med höga naturvärden.
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| 8. |
- Keogan, Katharine, et al.
(författare)
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Global phenological insensitivity to shifting ocean temperatures among seabirds
- 2018
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Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:4, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- Reproductive timing in many taxa plays a key role in determining breeding productivity(1), and is often sensitive to climatic conditions(2). Current climate change may alter the timing of breeding at different rates across trophic levels, potentially resulting in temporal mismatch between the resource requirements of predators and their prey(3). This is of particular concern for higher-trophic-level organisms, whose longer generation times confer a lower rate of evolutionary rescue than primary producers or consumers(4). However, the disconnection between studies of ecological change in marine systems makes it difficult to detect general changes in the timing of reproduction(5). Here, we use a comprehensive meta-analysis of 209 phenological time series from 145 breeding populations to show that, on average, seabird populations worldwide have not adjusted their breeding seasons over time (-0.020 days yr(-1)) or in response to sea surface temperature (SST) (-0.272 days degrees C-1) between 1952 and 2015. However, marked between-year variation in timing observed in resident species and some Pelecaniformes and Suliformes (cormorants, gannets and boobies) may imply that timing, in some cases, is affected by unmeasured environmental conditions. This limited temperature-mediated plasticity of reproductive timing in seabirds potentially makes these top predators highly vulnerable to future mismatch with lower-trophic-level resources(2).
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| 9. |
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| 10. |
- Moksnes, Per-Olav, et al.
(författare)
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Fritidsbåtars påverkan på grunda kustekosystem i Sverige
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sweden has a long and beautiful coastline with extensive archipelagos that offer exceptional conditions for recreational boating. There are more than 700 000 recreational boats in Sweden, which is one of the highest numbers in the world in relation to the population size. Small tidal differences and many sheltered bays also provide good conditions for storing boats at docks and piers and jetties. As a result, large areas of the Swedish coast are today covered with docks and marinas for recreational boats. The large number of boats and docks could have substantial negative effects on the environment. However, the understanding of the cumulative impact of recreational boating on Swedish coastal ecosystem has so far been incomplete. The goal with this report from the Swedish Institute for the Marine Environment has been to compile and summarize the present state of knowledge regarding how recreational boating affect shallow coastal ecosystems in Sweden, to determine the extent of the impact and if the development is sustainable. The aim has been to present scientific knowledge on these topics in an accessible way in order to facilitate the development of a more sustainable management of recreational boating in Sweden.The scientific literature strongly support that recreational boating generates many negative effects on the marine environment. Recreational boating requires a number of physical structures and generate a number activities that each results in several different pressures on the environment. An increased number of marinas, docks and dredged canals results in losses of important habitats, as well as long-term deterioration of the environmental conditions locally. Dredging and dumping of dredge material results in increased turbidity and dispersal of sediment, nutrients and pollutants over large areas with negative effects on many aquatic organisms, e.g. vegetation, fishes and mussels. Traffic from recreational boats and anchoring result in increased turbidity and sediment erosion as well as damage to habitats. Motor boats also create underwater noise that can disturb e.g. fishes, seals and porpoises. In addition, recreational boating result in substantial emissions of toxic substances and pollution from e.g. antifouling paint and combustion engines.More than 60% of all docks and marinas are found in wave sheltered, shallow (<3 m) areas with soft bottoms, despite that this environment only constitute 25% of shallow coastal areas in Sweden. These sheltered areas are well suited for storing boats, but also constitute one of the most productive and valuable environments along the coast. They are important environments for vegetation such as seagrass, pondweed and stoneworts, which in turn constitute important spawning and nursery areas for a large number of fish and invertebrates. The report shows that these shallow soft bottom environments are very sensitive to a majority of the stressors that recreational boating generate. Boating therefore create a disproportionally large impact on environments with high values.Although the impact from a single recreational boat or dock is limited, the cumulative effect is substantial because of the sheer number. According to recent inventories, there are today almost 110 000 docks along the Swedish coast covering almost 2 000 km of bottom. In comparison with the 1960s, the amount of docks has increased with almost 160%, which today constitutes an increase of 1 700 new docks per year. Recent studies show that vegetation is degraded as the number of docks and boats increase within shallow, wave sheltered areas. It is estimated that almost 20% of this important environment is negatively affected by recreational boating today; in the County of Stockholm and Västra Götaland around 30% of shallow, wave sheltered areas are estimated to be impacted. Despite several management measures in the last decades to decrease coastal exploitation, there are no signs that the rate of exploitation is decreasing.The large number of recreational boats with combustion engines, the trend of increasing engine size, and the fact that engines lack all forms of emission control result in substantial emissions of pollutants and greenhouse gases. Recent estimates suggest that the emissions from recreational boats are very high and comparable with other types of transport in Sweden. Emission of toxic copper from antifouling paint on recreational boats is also substantial and contributes to the high levels of copper in coastal waters, which is above the limit for good ecological status in 85% of the assessed coastal water bodies.Although most boat owners likely spend time at sea because they enjoy and care about the environment, the results presented in this report show that recreational boating have a substantial negative impact on the coastal environment, particularly in shallow, wave protected areas. In these areas, today’s use and development of recreational boating cannot be considered sustainable. However, the report also shows that there are ways to decrease the environmental impact from recreational boating. By changing the way we use and store recreational boats, and by improving management we can still allow coming generations to enjoy unexploited coastal environments with clear water and a rich plant and animal life.The report ends by discussing new, possible measures and solutions for a more sustainable use of recreational boats in Sweden, which could be a starting point for continuing such work. These include e.g. to identify vulnerable coastal environments in order to steer away exploitation and recreational boat traffic from these areas. By storing boats on land, the need for docks, dredging and toxic antifouling paint could decrease. Reduced speed limits and access limitations for recreational motorboats in certain areas could decrease negative impact on the most vulnerable habitats. Finally, new, environmentally friendly technology, and new financial instruments could be used to decrease negative impacts and create a more sustainable development of recreational boating.
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