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- Groenen, M. A., et al.
(författare)
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Analyses of pig genomes provide insight into porcine demography and evolution
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 491:7424, s. 393-398
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Tidskriftsartikel (refereegranskat)abstract
- For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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- Blacher, E., et al.
(författare)
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Potential roles of gut microbiome and metabolites in modulating ALS in mice
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7770
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder, in which the clinical manifestations may be influenced by genetic and unknown environmental factors. Here we show that ALS-prone Sod1 transgenic (Sod1-Tg) mice have a pre-symptomatic, vivarium-dependent dysbiosis and altered metabolite configuration, coupled with an exacerbated disease under germ-free conditions or after treatment with broad-spectrum antibiotics. We correlate eleven distinct commensal bacteria at our vivarium with the severity of ALS in mice, and by their individual supplementation into antibiotic-treated Sod1-Tg mice we demonstrate that Akkermansia muciniphila (AM) ameliorates whereas Ruminococcus torques and Parabacteroides distasonis exacerbate the symptoms of ALS. Furthermore, Sod1-Tg mice that are administered AM are found to accumulate AM-associated nicotinamide in the central nervous system, and systemic supplementation of nicotinamide improves motor symptoms and gene expression patterns in the spinal cord of Sod1-Tg mice. In humans, we identify distinct microbiome and metabolite configurations-including reduced levels of nicotinamide systemically and in the cerebrospinal fluid-in a small preliminary study that compares patients with ALS with household controls. We suggest that environmentally driven microbiome-brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.
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- Borel-Derlon, A., et al.
(författare)
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Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin (R)): a prospective study of 50 patients
- 2007
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:6, s. 1115-1124
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: A plasma-derived von Willebrand factor (VWF) concentrate with low factor VIII (FVIII) content was specifically developed to treat von Willebrand disease (VWD). Efficacy and safety were investigated by merging the results of two comparable protocols conducted prospectively in 5 European and 12 French centers. Methods and results: Fifty patients with clinically severe VWD (72% had VWF ristocetin cofactor activity less than 10 IU dL(-1) and 46% had FVIII < 20 IU dL(-1)) were treated with the concentrate as the only therapy, except for clinical situations requiring a priming dose of FVIII to rapidly correct an intrinsic coagulation defect. A total of 139 spontaneous bleeding episodes were treated; only 53 (38%) needed a concomitant FVIII dose. Outcome was excellent or good in 89% of the episodes. Forty-four patients underwent 108 surgical or invasive procedures. Outcome was excellent or good in 95 scheduled procedures (only VWF was infused) and 13 emergency procedures (a priming FVIII dose was co-administered with the first VWF infusion). There were no thrombotic complications and none of the 18 patients with type 3 VWD developed anti-VWF or anti-FVIII antibodies. Conclusions. This concentrate safely and effectively provides hemostasis in patients with clinically severe VWD.
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- Kwiecinski, Jakub, 1985, et al.
(författare)
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No rheumatoid arthritis in ancient Egypt: a reappraisal
- 2016
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Ingår i: Rheumatology International. - : Springer Science and Business Media LLC. - 0172-8172 .- 1437-160X. ; 36:6, s. 891-895
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Tidskriftsartikel (refereegranskat)abstract
- Antiquity of rheumatoid arthritis (RA) remains controversial, and its origins in Americas or in the Old World are disputed. Proponents of the latter frequently refer to RA in ancient Egypt, but validity of those claims has never been examined. Review of all reported RA cases from ancient Egypt revealed that none of them represent real RA, instead being either examples of changing naming conventions or of imprecise diagnostic criteria. Most cases represented osteoarthritis or spondyloarthropathies. Also review of preserved ancient Egyptian medical writings revealed many descriptions of musculoskeletal disorders, but none of them resembled RA. This suggests that RA was absent in ancient Egypt and supports the hypothesis of the New World origin of RA and its subsequent global spread in the last several centuries.
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| 9. |
- Lehner, B.A.E., et al.
(författare)
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End-to-end mission design for microbial ISRU activities as preparation for a moon village
- 2019
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Ingår i: Acta Astronautica. - : Elsevier. - 0094-5765 .- 1879-2030. ; 162, s. 216-226
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Tidskriftsartikel (refereegranskat)abstract
- In situ resource utilization (ISRU) increasingly features as an element of human long-term exploration and settlement missions to the lunar surface. In this study, all requirements to test a novel, biological approach for ISRU are validated, and an end-to-end mission architecture is proposed. The general mission consists of a lander with a fully autonomous bioreactor able to process lunar regolith and extract elemental iron. The elemental iron could either be stored or directly utilized to generate iron wires or construction material. To maximize the success rate of this mission, potential landing sites for future missions are studied, and technical details (thermal radiation, shielding, power-supply) are analyzed. The final section will assess the potential mission architecture (orbit, rocket, lander, timeframe). This design might not only be one step further towards an international “Moon Village”, but may also enable similar missions to ultimately colonize Mars and further explore our solar system.
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| 11. |
- Markovic, N., et al.
(författare)
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Severe traumatic lesions in the Late Neolithic cattle from the site of At-Vrsac, Serbia
- 2022
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Ingår i: International Journal of Osteoarchaeology. - : Wiley. - 1047-482X .- 1099-1212. ; 32:6, s. 1285-1294
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Tidskriftsartikel (refereegranskat)abstract
- This paper aims to assess the etiology and differential diagnosis of severe pathological lesions in wild and domestic cattle from the Late Neolithic site of At-Vrsac in the northeast part of the present-day Serbia. Excavations of this multilayered site revealed the remains of a Late Neolithic settlement belonging to the Vinca culture network of the Central Balkans. An aurochs metacarpal bone, two domestic cattle fragments of fused ulna and radius and of tibia, all with massive bone proliferations were recovered during the archaeological excavations in 1976. Paleopathological study was undertaken using an interdisciplinary approach, including AMS dating, radiography, computed tomography (CT), and histopathology. The results show severe oblique healed fracture with secondary pronounced bone reaction in the aurochs metacarpal bone and in the domestic cattle ulna-radius, while traumatic alteration infected with disseminated osteomyelitis was found in the domestic cattle tibia. These pathologies of wild and domestic cattle are discussed to reveal the level of environmental and human influence on the origin and development of the lesions in the Late Neolithic cattle.
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| 14. |
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| 15. |
- Volger, R., et al.
(författare)
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Mining moon & mars with microbes : Biological approaches to extract iron from Lunar and Martian regolith
- 2020
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Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 184
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Tidskriftsartikel (refereegranskat)abstract
- The logistical supply of terrestrial materials to space is costly and puts limitations on exploration mission scenarios. In-situ resource utilization (ISRU) can alleviate logistical requirements and thus enables sustainable exploration of space. In this paper, a novel approach to ISRU, utilizing microorganisms to extract iron from Lunar or Martian regolith, is presented. Process yields, and kinetics are used to verify the theoretical feasibility of applying four different microorganisms. Based on yields alone, three of the four organisms were not investigated further for use in biological ISRU. For the remaining organism, Shewanella oneidensis, the survivability impact of Martian regolith simulant JSC-MARS1 and Mars-abundant magnesium perchlorate were studied and found to be minimal. The payback time of the infrastructure installation needed for the process with S. oneidensis on Mars was analyzed and the sensitivity to various parameters was investigated. Water recycling efficiency and initial regolith concentration were found to be key to process performance. With a water recycling efficiency of 99.99% and initial regolith concentration of 300 g/L, leading to an iron concentration of approximately 44.7 g/L, a payback time of 3.3 years was found.
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