| 1. |
- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 2. |
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| 3. |
- Pettersson, K, et al.
(författare)
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Free and complexed prostate-specific antigen (PSA) : in vitro stability, epitope map, and development of immunofluorometric assays for specific and sensitive detection of free PSA and PSA-alpha 1-antichymotrypsin complex
- 1995
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Ingår i: Clinical Chemistry. - 0009-9147. ; 41:10, s. 8-1480
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Tidskriftsartikel (refereegranskat)abstract
- Generation of 15 monoclonal antibodies (MAbs) allowed construction of epitope maps and specific two-site immunofluorometric assays for free prostate-specific antigen (PSA) and PSA complexed with alpha 1-antichymotrypsin (ACT). Close correlation of PSA concentrations obtained with the use of different assays of free PSA suggested extensive similarity in immunodetection of free PSA in serum. Assays of the PSA-ACT complex overestimated the concentration of PSA-ACT in serum because of nonspecific adsorbance of ACT or cathepsin G-complexed ACT to the solid phase. This interference was substantially decreased in the presence of heparin. In studying the stability of purified PSA and PSA-ACT complexes formed in vitro, we found that the free PSA was stable during storage for 4 weeks at 35 degrees C, whereas PSA-ACT complexes largely dissociated in these conditions. The instability of PSA-ACT complexes was counteracted by storage at low temperatures, by adjusting the pH of the storage buffer between 6.8 and 7.4, and through addition of 100-1000-fold molar excess of native ACT. The ease of calibration and the accuracy of free PSA assays in comparison with assays of the PSA-ACT complex suggest that measurements of free to total PSA most accurately reflect the inverse of the proportion of PSA complexed to ACT in serum.
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| 4. |
- Christensson, A, et al.
(författare)
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Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer
- 1993
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Ingår i: Journal of Urology. - 1527-3792. ; 150:1, s. 100-105
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Tidskriftsartikel (refereegranskat)abstract
- Prostate specific antigen (PSA) in serum has recently been shown to occur in complex with alpha 1-antichymotrypsin and as an approximately 30 kDa. noncomplexed molecular form. We characterized PSA by 3 different assays in samples from 144 patients with benign prostatic hyperplasia (BPH) and 121 with carcinoma of the prostate. One of these noncompetitive assays measured total PSA by detecting PSA complexed to serine proteinase inhibitors and the noncomplexed molecular form, a second measured only PSA in complex with alpha 1-antichymotrypsin, whereas a third detected the noncomplexed form. PSA in complex with alpha 1-antichymotrypsin was the predominant form in all patient sera. Noncomplexed PSA constituted a minor fraction that was significantly smaller in patients with untreated prostate cancer than in those with BPH (p < 0.0001). The proportion of noncomplexed PSA does not correlate to the serum concentration of PSA or that of alpha 1-antichymotrypsin. In men with a serum PSA concentration of less than 10 micrograms./l. the combination of assays measuring total PSA immunoreactivity, the noncomplexed molecular form and PSA in complex with alpha 1-antichymotrypsin may facilitate discrimination between prostate cancer and BPH.
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| 5. |
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| 6. |
- Lilja, H, et al.
(författare)
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Prostate-specific antigen in serum occurs predominantly in complex with alpha 1-antichymotrypsin
- 1991
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 37:9, s. 25-1618
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Tidskriftsartikel (refereegranskat)abstract
- Immunologic measurements of the serum concentration of prostate-specific antigen (PSA), an abundant prostatic-secreted serine proteinase, are frequently used to monitor patients with prostate cancer, though it has not been ascertained whether this immunoreactivity represents a PSA zymogen, the active proteinase, or PSA complexed to extracellular proteinase inhibitors. To characterize the PSA immunoreactivity in serum, we used monoclonal antibodies produced against PSA and a polyclonal rabbit IgG against alpha 1-antichymotrypsin in the design of three noncompetitive PSA assays: assay T, which detected PSA both when present as the active proteinase and when complexed to alpha 1-antichymotrypsin; assay F, which recognized the active proteinase but most poorly detected PSA complexed to alpha 1-antichymotrypsin; and assay C, which was specific for PSA complexed to alpha 1-antichymotrypsin. We used the three assays to measure PSA immunoreactivity in 64 patients' sera and in the effluent after gel chromatography of sera from four patients. This identified an 80- to 90-kDa complex between PSA and alpha 1-antichymotrypsin as the predominant fraction of the PSA immunoreactivity in blood plasma; an immunoreactive 25- to 40-kDa compound was the minor fraction.
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| 7. |
- Bolelli, G., et al.
(författare)
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Sliding and abrasive wear behaviour of HVOF- and HVAF-sprayed Cr3C2-NiCr hardmetal coatings
- 2016
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Ingår i: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 358-359, s. 32-50
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Tidskriftsartikel (refereegranskat)abstract
- This paper provides a comprehensive characterisation of HVOF- and HVAF-sprayed Cr3C2–25 wt.% NiCr hardmetal coatings. One commercial powder composition with two different particle size distributions was processed using five HVOF and HVAF thermal spray systems.All coatings contain less Cr3C2 than the feedstock powder, possibly due to the rebound of some Cr3C2-rich particles during high-velocity impact onto the substrate.Dry sand-rubber wheel abrasive wear testing causes both grooving and pull-out of splat fragments. Mass losses depend on inter- and intra-lamellar cohesion, being higher (≥70 mg after a wear distance of 5904 m) for the coatings deposited with the coarser feedstock powder or with one type of HVAF torch.Sliding wear at room temperature against alumina involves shallower abrasive grooving, small-scale delamination and carbide pull-outs, and it is controlled by intra-lamellar cohesion. The coatings obtained from the fine feedstock powder exhibit the lowest wear rates (≈5x10−6 mm3/(Nm)). At 400 °C, abrasive grooving dominates the sliding wear behaviour; wear rates increase by one order of magnitude but friction coefficients decrease from ≈0.7 to ≈0.5. The thermal expansion coefficient of the coatings (11.08x10−6 °C−1 in the 30–400 °C range) is sufficiently close to that of the steel substrate (14.23x10−6 °C−1) to avoid macro-cracking
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| 8. |
- Bolelli, G., et al.
(författare)
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Tribology of HVOF- and HVAF-sprayed WC-10Co4Cr hardmetal coatings : A comparative assessment
- 2015
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Ingår i: Surface and Coatings Technology. - : Elsevier. - 0257-8972. ; 265, s. 125-144
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Tidskriftsartikel (refereegranskat)abstract
- his paper provides a comprehensive assessment of the sliding and abrasive wear behaviour of WC–10Co4Cr hardmetal coatings, representative of the existing state-of-the-art. A commercial feedstock powder with two different particle size distributions was sprayed onto carbon steel substrates using two HVOF and two HVAF spray processes.Mild wear rates of < 10-7 mm3/(Nm) and friction coefficients of ≈ 0.5 were obtained for all samples in ball-on-disk sliding wear tests at room temperature against Al2O3 counterparts. WC–10Co4Cr coatings definitely outperform a reference electrolytic hard chromium coating under these test conditions. Their wear mechanisms include extrusion and removal of the binder matrix, with the formation of a wavy surface morphology, and brittle cracking. The balance of such phenomena is closely related to intra-lamellar features, and rather independent of those properties (e.g. indentation fracture toughness, elastic modulus) which mainly reflect large-scale inter-lamellar cohesion, as quantitatively confirmed by a principal component analysis. Intra-lamellar dissolution of WC into the matrix indeed increases the incidence of brittle cracking, resulting in slightly higher wear rates. At 400 °C, some of the hardmetal coatings fail because of the superposition between tensile residual stresses and thermal expansion mismatch stresses (due to the difference between the thermal expansion coefficients of the steel substrate and of the hardmetal coating). Those which do not fail, on account of lower residual stresses, exhibit higher wear rates than at room temperature, due to oxidation of the WC grains.The resistance of the coatings against abrasive wear, assessed by dry sand–rubber wheel testing, is related to inter-lamellar cohesion, as proven by a principal component analysis of the collected dataset. Therefore, coatings deposited from coarse feedstock powders suffer higher wear loss than those obtained from fine powders, as brittle inter-lamellar detachment is caused by their weaker interparticle cohesion, witnessed by their systematically lower fracture toughness as well.
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| 9. |
- Bulanova, Daria, et al.
(författare)
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Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
- 2017
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.
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| 10. |
- Matikainen, N., et al.
(författare)
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Hepatic Lipogenesis and a Marker of Hepatic Lipid Oxidation, Predict Postprandial Responses of Triglyceride-rich Lipoproteins
- 2014
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 22:8, s. 1854-1859
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivePostprandial hypertriglyceridemia is an important risk factor for cardiovascular disease. The mechanisms are still unclear. Here it was tested if hepatic de novo lipogenesis (DNL) and lipid oxidation influence the postprandial responses of triglyceride-rich lipoproteins (TRL) in humans. MethodsThe contribution of hepatic DNL to hepatic TRL production was analyzed in 67 men and women with a moderate range of BMI after a fat-rich meal. Also, lipase activities, liver fat, and 3-OH-butyrate were quantitated as an indicator of -oxidation. Lipoproteins and metabolic markers were measured in fasting and postprandial blood samples. ResultsPostprandial DNL correlates with postprandial TG and apolipoprotein (apo) C-III responses in plasma and with TG, apoB48 and apoB100 responses in TRLs and their larger remnant particles. Fasting and 8-h postprandial DNL was inversely related to 3-OH-butyrate but not to liver fat content. Fasting apoC-III and 3-OH-butyrate, but not liver fat, independently predicted fasting DNL. ConclusionsThe fasting and 8-h postprandial rate of DNL was inversely associated with the hepatic lipid oxidation in humans. DNL contributes significantly to the TG content in TRLs but not to the amount of liver fat, suggesting that an imbalance between DNL and fat oxidation contributes to postprandial atherogenic dyslipidemia.
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