| 1. |
- Bongers, B. J., et al.
(författare)
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Pan-cancer functional analysis of somatic mutations in G protein-coupled receptors
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- G Protein-coupled receptors (GPCRs) are the most frequently exploited drug target family, moreover they are often found mutated in cancer. Here we used a dataset of mutations found in patient samples derived from the Genomic Data Commons and compared it to the natural human variance as exemplified by data from the 1000 genomes project. We explored cancer-related mutation patterns in all GPCR classes combined and individually. While the location of the mutations across the protein domains did not differ significantly in the two datasets, a mutation enrichment in cancer patients was observed among class-specific conserved motifs in GPCRs such as the Class A "DRY" motif. A Two-Entropy Analysis confirmed the correlation between residue conservation and cancer-related mutation frequency. We subsequently created a ranking of high scoring GPCRs, using a multi-objective approach (Pareto Front Ranking). Our approach was confirmed by re-discovery of established cancer targets such as the LPA and mGlu receptor families, but also discovered novel GPCRs which had not been linked to cancer before such as the P2Y Receptor 10 (P2RY10). Overall, this study presents a list of GPCRs that are amenable to experimental follow up to elucidate their role in cancer.
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| 2. |
- Humphreys, Ben A., et al.
(författare)
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The Influence of pH on the Lipase Digestion of Nanosized Triolein, Diolein and Monoolein films
- 2022
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Ingår i: Frontiers in Soft Matter. - : Frontiers Media SA. - 2813-0499. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Herein we studied the processes at the liquid aqueous interface at pH 7 and 8.5 during Thermomyces lanuginosus lipase-catalyzed hydrolysis of nanosized tri-, di- and mono-olein films deposited on a planar substrate. By employing a combination of ellipsometry, QCM-D and ATR-FTIR, we were able to reveal the physical properties of the thin films at high time resolution throughout the initial hydration and subsequent digestion, as well as the main chemical species present before and after lipolysis. The ATR-FTIR results showed that the degree of digestion and protonated state of the oleic acid produced in the reaction are highly dependent on the pH of the aqueous solvent. Furthermore, the ellipsometry and QCM-D results reveal that the duration of the lag phase observed before lipolysis was detected and the magnitude and type of changes to the physical properties of the thin films throughout digestion was influenced by whether the initial substrate consisted of tri-, di- or mono-olein.
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