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- Gusev, A, et al.
(författare)
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
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Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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- Loughran, MG, et al.
(författare)
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Ammonium ion requirement and stability of methanol dehydrogenase TTF TCNQ electrodes
- 1996
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Ingår i: The Analyst. - : Royal Society of Chemistry. - 0003-2654 .- 1364-5528. ; 121:11, s. 1711-1715
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Tidskriftsartikel (refereegranskat)abstract
- The ammonium ion requirement and stability of quinoprotein methanol dehydrogenases were investigated with a view to incorporating them in enzyme electrodes for alcohol. This involved consideration of the effect of temperature and polyelectrolytes on enzyme stability. A packed cavity electrode was constructed using the organic conducting salt TTF-TCNQ (tetrathiafulvalene-tetracyanoquinodimethane). Methanol dehydrogenase isolated from Paracoccus denitrificans was more stable than the enzyme isolated from Methylophilus methylotrophus and was successfully used for repeated assay in packed cavity electrodes without significant loss in current output. These investigations also showed that, contrary to suggestions in the literature, ammonium ions are necessary for efficient re-oxidation of methanol dehydrogenase at the organic conducting salt electrode.
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- LOUGHRAN, MG, et al.
(författare)
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AMPEROMETRIC DETECTION OF HISTAMINE AT A QUINOPROTEIN DEHYDROGENASE ENZYME ELECTRODE
- 1995
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Ingår i: Biosensors & bioelectronics. - : Elsevier Science B.V., Amsterdam.. - 0956-5663 .- 1873-4235. ; 10:07-jun, s. 569-576
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Tidskriftsartikel (refereegranskat)abstract
- Methylamine dehydrogenase, a tryptophan tryptophyl quinone (TTQ) containing quinoprotein, catalyzes the oxidation of a variety of primary aliphatic monoamines and diamines to their respective aldehydes and ammonia. This paper reports the construction and characterization of an enzyme electrode capable of detecting histamine and methylamine at +200 mV versus a saturated calomel reference electrode. The methylamine dehydrogenase isolated from Paracoccus denitrificans was used in conjunction with the insoluble mediator tetracyanoquinodimethane (TCNQ) to construct enzyme electrodes which will potentially provide simple rapid analysis of histamine without the need for the extensive sample pretreatments currently required in HPLC and GLC analysis. The linear response of this amperometric sensor, between 0 and 200 mu M, correlates well with elevated histamine levels predominant in patients with chronic myelogenous leukaemia, whilst the observed limit of detection, 4.8 mu M, compares favourably with the lower limits of detection reported for a potentiometric histamine sensitive enzyme electrode.
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