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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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- 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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- van Rijn, Jorik M., et al.
(författare)
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Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:21
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Tidskriftsartikel (refereegranskat)abstract
- Hyaline fibromatosis syndrome (HFS), resulting from ANTXR2 mutations, is an ultra-rare disease that causes intestinal lymphangiectasia and protein-losing enteropathy (PLE). The mechanisms leading to the gastrointestinal phenotype in these patients are not well defined. We present two patients with congenital diarrhea, severe PLE and unique clinical features resulting from deleterious ANTXR2 mutations. Intestinal organoids were generated from one of the patients, along with CRISPR-Cas9 ANTXR2 knockout, and compared with organoids from two healthy controls. The ANTXR2-deficient organoids displayed normal growth and polarity, compared to controls. Using an anthrax-toxin assay we showed that the c.155C>T mutation causes loss-of-function of ANTXR2 protein. An intrinsic defect of monolayer formation in patient-derived or ANTXR2(KO) organoids was not apparent, suggesting normal epithelial function. However, electron microscopy and second harmonic generation imaging showed abnormal collagen deposition in duodenal samples of these patients. Specifically, collagen VI, which is known to bind ANTXR2, was highly expressed in the duodenum of these patients. In conclusion, despite resistance to anthrax-toxin, epithelial cell function, and specifically monolayer formation, is intact in patients with HFS. Nevertheless, loss of ANTXR2-mediated signaling leads to collagen VI accumulation in the duodenum and abnormal extracellular matrix composition, which likely plays a role in development of PLE.
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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, s. 474-
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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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- Buda, V., et al.
(författare)
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C18 Dienes as attractants for eighteen clearwing (Sesiidae), tineid (Tineidae), and choreutid (Choreutidae) moth species
- 1993
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Ingår i: Journal of Chemical Ecology. - 0098-0331 .- 1573-1561. ; 19:4, s. 799-813
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Tidskriftsartikel (refereegranskat)abstract
- By screening singly and binary mixed 2,13- and 3,13-octadecadien-yl acetates and alcohols (2,13- and 3,13-18: Ac/OH)in Lithuania, Armenia, Azerbaijan, Turkmenistan, Ukraine, and the far east of Russia, sex attractants were discovered for 12 Sesiidae, four Tineidae, and one Choreutidae moth species. Males of Sesia yezoensis and Bembecia puella as well as Nemapogon flavifrons were attracted by mixture of Z3,Z13-18:Ac/OH in a ratio of 9:1, Pyropteron sp. n. by the same mixture (ratio 1:9), Bembecia romanovi and B. zuwandica by Z3,Z13-18:AC and E3,Z13-18:Ac (9:1), Synanthedon caucasicum by the same mixture in the opposite ratio (1:9), B. scopigera by 23,213-18:Ac and E2,Z13-18:OH in a ratio 9:1, Synasphecia triannuliformis by Z3,Z13-18:OH and E3,Z13-18:OH (9: 1), Similipepsis takizawai and Archimeessia sp. n. by E3,Z13-18:OH and E2,Z13-18:Ac (1:1), Prochoreutis sechestediana by a mixture of E3,Z13-18:Ac plus E2,Z13-18:OH (1:), Microsphecia brosiformis by E3,Z13-18:Ac, Synanthedon conopiformis by the analogous alcohol, Synanthedon scoliaeformis and Nemaxera betulinella by E2,Z13-18:Ac, Triaxomera fulvimitrella by Z3,Z13-18:Ac. An analogous alcohol component is essential for the attraction of B. ichneumoniformis males. Inhibitors for B. romanovi, B. scopigera and B. zuwandica attraction were discovered. Preliminary data on attractants for six other species as well as on the diurnal rhythm of sexual activity of three species are presented. A new method for the stereoselective synthesis of 3,13-18:Ac/OH and E2,Z13-18:Ac/OH is described.
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