| 1. |
- Kurilshikov, Alexander, et al.
(författare)
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Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
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Tidskriftsartikel (refereegranskat)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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| 2. |
- Ma, Li-Jun, et al.
(författare)
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Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7287, s. 367-73
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Tidskriftsartikel (refereegranskat)abstract
- Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
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| 3. |
- Mohammed Taha, Hiba, et al.
(författare)
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The NORMAN Suspect List Exchange (NORMAN-SLE) : facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry
- 2022
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 34:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
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| 4. |
- Boon, Hanneke, 1981-, et al.
(författare)
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Substrate Source Use in Older, Trained Males after Decades of Endurance Training
- 2007
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Ingår i: Medicine & Science in Sports & Exercise. - Philadelphia, PA : Lippincott Williams & Wilkins. - 0195-9131 .- 1530-0315. ; 39:12, s. 2160-2170
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this study was to compare substrate source use in older, long-term exercising, endurance-trained males with sedentary controls. METHODS: [U-C]palmitate and [6,6-H2]glucose tracers were applied to assess plasma free fatty acid (FFA) and glucose oxidation rates, and to estimate muscle- and/or lipoprotein-derived triacylglycerol (TG) and muscle glycogen use. Subjects were 10 long-term exercising, endurance-trained males and 10 sedentary controls (age 57 +/- 1 and 60 +/- 2 yr, respectively). Muscle biopsy samples were collected before and after exercise to assess muscle fiber type-specific intramyocellular lipid and glycogen content. RESULTS: During exercise, plasma palmitate Ra, Rd, and Rox were significantly greater in the trained subjects compared with the controls (Ra: 0.36 +/- 0.02 and 0.25 +/- 0.02; Rd: 0.36 +/- 0.03 and 0.24 +/- 0.02; Rox: 0.31 +/- 0.02 and 0.20 +/- 0.02 mmol.min, respectively, P < 0.01). This resulted in greater plasma FFA and total fat oxidation rates in the trained versus sedentary subjects (P < 0.001). Muscle- and/or lipoprotein-derived TG use contributed 10 +/- 2 and 11 +/- 3% in the trained and control groups, respectively (NS). No significant net changes in muscle fiber lipid content were observed. CONCLUSIONS: Older, endurance-trained males oxidize more fat during moderate-intensity exercise than do sedentary controls. This greater total fat oxidation rate is attributed to a higher plasma FFA release, uptake, and oxidation rate. In contrast, intramyocellular triacylglycerol does not seem to represent a major substrate source during 1 h of moderate-intensity exercise in older trained or sedentary men. ©2007 The American College of Sports Medicine.
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| 5. |
- Stellingwerff, Trent, et al.
(författare)
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Significant intramyocellular lipid use during prolonged cycling in endurance-trained males as assessed by three different methodologies
- 2007
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - Bethesda, MD : American Physiological Society. - 0193-1849 .- 1522-1555. ; 292:6, s. E1715-E1723
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Tidskriftsartikel (refereegranskat)abstract
- Intramyocellular triacylglycerol (IMTG) has been suggested to represent an important substrate source during exercise. In the present study, IMTG utilization during exercise is assessed through the use of various methodologies. In addition, we identified differences in the use of intramyocellular lipids deposited in the immediate subsarcolemmal (SS) area and those stored in the more central region of the fiber. Contemporary stable isotope technology was applied in combination with muscle tissue sampling before and immediately after 3 h of moderate-intensity cycling exercise (62 ± 2% V̇o2 max) in eight well-trained male cyclists. Continuous infusions with [U-13C]palmitate and [6,6-2H2]glucose were applied to quantify plasma free fatty acid (FFA) and glucose oxidation rates and to estimate whole body IMTG and glycogen use. Both immunohistochemical analyses of oil red O (ORO)-stained muscle cross sections and biochemical triacylglycerol (TG) extraction were performed to assess muscle lipid content. During exercise, plasma FFA, muscle (and/or lipoprotein)-derived TG, plasma glucose, and muscle glycogen oxidation contributed 24 ± 2, 22 ± 3, 11 ± 1, and 43 ± 3% to total energy expenditure, respectively. In accordance, a significant net decline in muscle lipid content was observed following exercise as assessed by ORO staining (67 ± 8%) and biochemical TG extraction (49 ± 8%), and a positive correlation was observed between methods (r = 0.56; P < 0.05). Lipid depots located in the SS area were utilized to a greater extent than the more centrally located depots. This is the first study to show significant use of IMTG as a substrate source during exercise in healthy males via the concurrent implementation of three major methodologies. In addition, this study shows differences in resting subcellular intramyocellular lipid deposit distribution and in the subsequent net use of these deposits during exercise. Copyright © 2007 the American Physiological Society.
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