ORCID Profile
0000-0003-4267-2051
Current Organisations
Royal Botanic Gardens Kew
,
University of Cambridge
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-04-2022
DOI: 10.1002/HEP4.1955
Abstract: Genome‐wide association studies in adults have identified variants in hydroxysteroid 17‐beta dehydrogenase 13 ( HSD17B13 ) and mitochondrial amidoxime reducing component 1 ( MTARC1 ) as protective against nonalcoholic fatty liver disease (NAFLD). We aimed to test their association with pediatric NAFLD liver histology and investigate their function using metabolomics. A total of 1450 children (729 with NAFLD, 399 with liver histology) were genotyped for rs72613567T TA in HSD17B13 , rs2642438G A in MTARC1 , and rs738409C G in patatin‐like phospholipase domain‐containing protein 3 ( PNPLA3 ). Genotype–histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of children. We found rs72613567T TA in HSD17B13 to be associated with lower odds of NAFLD diagnosis (odds ratio, 0.7 95% confidence interval, 0.6–0.9) and a lower grade of portal inflammation ( p 0.001). rs2642438G A in MTARC1 was associated with a lower grade of hepatic steatosis ( p = 0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective ‐TA allele. MTARC1 levels were unaffected by genotype. Both variants were associated with down‐regulation of fibrogenic pathways. HSD17B13 perturbs plasma phosphatidylcholines and triglycerides. In silico modeling suggested p.Ala165Thr disrupts the stability and metal binding of MTARC1 . Conclusion: Both HSD17B13 and MTARC1 variants are associated with less severe pediatric NAFLD. These results provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD.
Publisher: Springer Science and Business Media LLC
Date: 26-01-2013
DOI: 10.1007/S12154-012-0090-1
Abstract: In this paper we report the molecular profiling, lipidome and proteome, of the plant organelle known as an oil body (OB). The OB is remarkable in that it is able to perform its biological role (storage of triglycerides) whilst resisting the physical stresses caused by changes during desiccation (dehydration) and germination (rehydration). The molecular profile that confers such extraordinary physical stability on OBs was determined using a combination of 31 P/ 1 H nuclear magnetic resonance (NMR), high-resolution mass spectrometry and nominal mass-tandem mass spectrometry for the lipidome, and gel-electrophoresis-chromatography-tandem mass spectrometry for the proteome. The integrity of the procedure for isolating OBs was supported by physical evidence from small-angle neutron-scattering experiments. Suppression of lipase activity was crucial in determining the lipidome. There is conclusive evidence that the latter is dominated by phosphatidylcholine (∼60 %) and phosphatidylinositol (∼20 %), with a variety of other head groups (∼20 %). The fatty acid profile of the surface monolayer comprised palmitic, linoleic and oleic acids (2:1:0.25, 1 H NMR) with only traces of other fatty acids (C24:0, C22:0, C18:0, C18:3, C16:2 by MS). The proteome is rich in oleosins (78 %) with the remainder being made up of caleosins and steroleosins. These data are sufficiently detailed to inform an update of the understood model of this organelle and can be used to inform the use of such components in a range of molecular biological, biotechnological and food industry applications. The techniques used in this study for profiling the lipidome throw a new light on the lipid profile of plant cellular compartments.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Samuel Furse.