| 1. |
- Rydin, Emil, et al.
(författare)
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Contrasting distribution and speciation of sedimentary organic phosphorus among different basins of the Baltic Sea
- 2023
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 68:4, s. 767-779
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Tidskriftsartikel (refereegranskat)abstract
- Recycling of phosphorus (P) from deoxygenated sediments perpetuates eutrophic conditions in parts of the Baltic Sea. Sedimentary organic P is a major source of dissolved P to the water column, but also a sink for permanent P burial. The mechanisms behind these two pathways are, however, largely unknown. Using new methods, we determined P in DNA and phospholipids, which are both found in all organisms. We also identified inositol phosphates that are particularly important in eukaryotes. Sediment cores were collected from contrasting basins in the Baltic Sea to study their relative contribution to the total P pool. We found high DNA-P/phospholipid-P ratios in surface sediments from the Bothnian Bay and Bothnian Sea. However, these ratios were low throughout profiles in euxinic Baltic Proper sediments. The elevated ratios present in sediments overlain by oxic bottom waters might indicate the presence of a microbial community stimulated by bioturbation, whereas the low DNA-P/phospholipid-P ratios in Baltic Proper sediments likely indicate an energy-limited microbial community, typical to the "deep biosphere" environment. Inositol-P was almost absent in euxinic Baltic Proper sediments that had a low total P amount compared to those in the other basins. We suggest that variability in the composition of sedimentary microbial communities among the Baltic Sea basins might cause differences in organic P forms that in turn affects its turnover.
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| 2. |
- Gabrielson, Marike, et al.
(författare)
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Inclusion of Plasma Prolactin Levels in Current Risk Prediction Models of Premenopausal and Postmenopausal Breast Cancer
- 2018
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Ingår i: JNCI CANCER SPECTRUM. - : OXFORD UNIV PRESS. - 2515-5091. ; 2:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating plasma prolactin is associated with breast cancer risk and may improve our ability to identify high-risk women. Mammographic density is a strong risk factor for breast cancer, but the association with prolactin is unclear. We studied the association between breast cancer, established breast cancer risk factors and plasma prolactin, and improvement of risk prediction by adding prolactin. Methods: We conducted a nested case-control study including 721 breast cancer patients and 1400 age-matched controls. Plasma prolactin levels were assayed using immunoassay and mammographic density measured by STRATUS. Odds ratios (ORs) were calculated by multivariable adjusted logistic regression, and improvement in the area under the curve for the risk of breast cancer by adding prolactin to established risk models. Statistical tests were two-sided. Results: In multivariable adjusted analyses, prolactin was associated with risk of premenopausal (OR, top vs bottom quintile = 1.9; 1.88 (95% confidence interval [CI] = 1.08 to 3.26) but not with postmenopausal breast cancer. In postmenopausal cases prolactin increased by 10.6% per cBIRADS category (P-trend = .03). In combined analyses of prolactin and mammographic density, ORs for women in the highest vs lowest tertile of both was 3.2 (95% CI = 1.3 to 7.7) for premenopausal women and 2.44 (95% CI = 1.44 to 4.14) for postmenopausal women. Adding prolactin to current risk models improved the area under the curve of the Gail model (+2.4 units, P = .02), Tyrer-Cuzick model (+3.8, P = .02), and the CAD2Y model (+1.7, P = .008) in premenopausal women. Conclusion: Circulating plasma prolactin and mammographic density appear independently associated with breast cancer risk among premenopausal women, and prolactin may improve risk prediction by current risk models.
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| 3. |
- Ubhayasekera, S. J. Kumari A., et al.
(författare)
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Simultaneous quantification of imatinib and CGP74588 in human plasma by liquid chromatography-time of flight mass spectrometry (LC-TOF-MS)
- 2016
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Ingår i: Analytical Methods. - : Royal Society of Chemistry (RSC). - 1759-9660 .- 1759-9679. ; 8:15, s. 3046-3054
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Tidskriftsartikel (refereegranskat)abstract
- Imatinib mesylate is widely used for the treatment of different types of cancer, such as chronic myelogenous leukemia and gastrointestinal stromal tumors. It is a tyrosine kinase inhibitor that binds to the active site of the enzyme inhibiting it. In clinical toxicology, a fast and sensitive quantification method for monitoring the imatinib concentration in blood can be very useful for personalized treatments. The aim of this study was to propose an alternative novel analytical method (LC-TOF-MS) for the quantification of intracellular imatinib and its main metabolite in human plasma. The method is simple and fast. It has sufficient sensitivity for the quantification of imatinib and its main metabolite CGP74588 in a smaller volume of plasma. The linearity of the method was evaluated over the range of concentrations (0.02-5 mu g mL(-1)) of imatinib and CGP74588 in human plasma. The correlation coefficients (r(2)) were close to 1 for both analytes. The limit of quantification was 0.02 mu g mL(-1) for both imatinib and CGP74588. A number of (>50) chronic myelogenous leukemia patient plasma samples have been analyzed by this method obtaining values ranging from 0.19-4.53 and 0.03-0.84 mu g mL(-1) for imatinib and CGP74588, respectively. This novel method allows a specific, sensitive and reliable simultaneous determination of intracellular imatinib and CGP74588 in a single chromatographic run, which is suitable for routine clinical practice.
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| 4. |
- Dubois, Louise, et al.
(författare)
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Proteomic profiling of detergent resistant membranes (lipid rafts) of prostasomes
- 2015
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 14:11, s. 3015-3022
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Tidskriftsartikel (refereegranskat)abstract
- Prostasomes are exosomes derived from prostate epithelial cells through exocytosis by multivesicular bodies. Prostasomes have a bilayered membrane and readily interact with sperm. The membrane lipid composition is unusual with a high contribution of sphingomyelin at the expense of phosphatidylcholine and saturated and monounsaturated fatty acids are dominant. Lipid rafts are liquid-ordered domains that are more tightly packed than the surrounding non-raft phase of the bilayer. Lipid rafts are proposed to be highly dynamic, submicroscopic assemblies that float freely within the liquid disordered membrane bilayer and some proteins preferentially partition into the ordered raft domains. We asked the question whether lipid rafts do exist in prostasomes and, if so, which proteins might be associated with them. Prostasomes of density range 1.13-1.19g/mL were subjected to density gradient ultracentrifugation in sucrose fabricated by phosphate buffered saline (PBS) containing 1% Triton X-100 with capacity for banding at 1.10g/mL, i.e. the classical density of lipid rafts. Prepared prostasomal lipid rafts (by gradient ultracentrifugation) were analyzed by mass spectrometry and electron microscopy. The clearly visible band on top of 1.10g/mL sucrose in the Triton X-100 containing gradient was subjected to LC-MS/MS and more than 370 lipid raft associated proteins were identified. Several of them were involved in intraluminal vesicle formation, e.g. tetraspanins, ESCRTs and Ras-related proteins. This is the first comprehensive LC-MS/MS profiling of proteins in lipid rafts derived from exosomes. Data are available via ProteomeXchange with identifier PXD002163.
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| 5. |
- Ek, Pia, et al.
(författare)
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Phosphohistidine phosphatase 1 (PHPT1) also dephosphorylates phospholysine of chemically phosphorylated histone H1 and polylysine
- 2015
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:1, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Background. Phosphohistidine phosphatase 1 (PHPT1), also named protein histidine phosphatase (PHP), is a eukaryotic enzyme dephosphorylating proteins and peptides that are phosphorylated on a histidine residue. A preliminary finding that histone H1, which lacks histidine, was phosphorylated by phosphoramidate and dephosphorylated by PHPT1 prompted the present investigation. Methods. Histone H1 and polylysine were phosphorylated at a low concentration (3.9 mM) of phosphoramidate. Their dephosphorylation by recombinant human PHPT1 was investigated by using a DEAE-Sepharose spin column technique earlier developed by us for studies on basic phosphoproteins and phosphopeptides. Determination of protein-bound, acid-labile phosphate was performed by a malachite green method. Mass spectrometry (MS) was used to investigate the occurrence of N-epsilon-phospholysine residues in a phosphorylated histone H 1.2 preparation, and to measure the activity of PHPT1 against free N-omega-phosphoarginine. Results. Histone H1.2, which lacks histidine, was phosphorylated by phosphoramidate on several lysine residues, as shown by MS. PHPT1 was shown to dephosphorylate phosphohistone H1 at a rate similar to that previously described for the dephosphorylation of phosphohistidine-containing peptides. In addition, phosphopolylysine was an equally good substrate for PHPT1. However, no dephosphorylation of free phosphoarginine by PHPT1 could be detected. Conclusion. The finding that PHPT1 can dephosphorylate phospholysine in chemically phosphorylated histone H1 and polylysine demonstrates a broader specificity for this enzyme than known so far.
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| 6. |
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| 7. |
- Timmusk, Salme, et al.
(författare)
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Sfp-type PPTase inactivation promotes bacterial biofilm formation and ability to enhance wheat drought tolerance
- 2015
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Paenibacillus polymyxa is a common soil bacterium with broad range of practical applications. An important group of secondary metabolites in P polymyxa are non-ribosomal peptide and polyketide derived metabolites (NRPs/PKs). Modular non-ribosomal peptide synthetases catalyze main steps in the biosynthesis of the complex secondary metabolites. Here we report on the inactivation of an A26 Sfp-type 4'-phosphopantetheinyl transferase (Sfp-type PPTase). The inactivation of the gene resulted in loss of NRPs/PKs production. In contrast to the former Bacillus spp. model the mutant strain compared to wild type showed greatly enhanced biofilm formation ability. A26 Delta sfp biofilm promotion is directly mediated by NRPs/PKs, as exogenous addition of the wild type metabolite extracts restores its biofilm formation level. Wheat inoculation with bacteria that had lost their Sfp-type PPTase gene resulted in two times higher plant survival and about three times increased biomass under severe drought stress compared to wild type. Challenges with P. polymyxa genetic manipulation are discussed.
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| 8. |
- Kask, Lena, et al.
(författare)
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Identification of Novel Downstream Molecules of Tissue Factor Activation by Comparative Proteomic Analysis
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:2, s. 477-488
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Tidskriftsartikel (refereegranskat)abstract
- Tissue factor (TF) is both an initiator of blood coagulation and a signaling receptor. Using a proteomic approach, we investigated the role of TF in cell signaling when stimulated by its ligand, activated factor VII (FVIIa). From a 2-D difference gel electrophoresis (DIGE) study we found forty one spots that were differentially regulated over time in FVIIa stimulated cells or in comparison to nonstimulated cells. Mass spectrometry identifies 23 out of these as 13 different proteins. One of them, elongation factor 2 (EF-2), was investigated in greater detail by Western blot, a protein synthesis assay and cell cycle analysis. When tissue factor was stimulated by FVIIa, the phosphorylation of EF-2 increased which inactivates this protein. Analyzing the effect using site inactivated FVIIa (FVIIai), as well as the protease activated receptor 2 (PAR-2) agonist SLIGKV, indicated that the inactivation was not PAR-2 dependent. A panel of tissue factor mutants was analyzed further to try to pinpoint what part of the cytoplasmic domain that is needed for this effect. Performing a protein synthesis assay in two different cell lines we could confirm that protein synthesis decreased upon stimulation by FVIIa. Cell cycle analysis showed that FVIIa also promotes a higher degree of cell proliferation.
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| 9. |
- Bozaykut, Perinur, et al.
(författare)
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The role of heat stress on the age related protein carbonylation
- 2013
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 89, s. 238-254
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Tidskriftsartikel (refereegranskat)abstract
- Since the proteins are involved in many physiological processes in the organisms, modifications of proteins have important outcomes. Protein modifications are classified in several ways and oxidative stress related ones take a wide place. Aging is characterized by the accumulation of oxidized proteins and decreased degradation of these proteins. On the other hand protein turnover is an important regulatory mechanism for the control of protein homeostasis. Heat shock proteins are a highly conserved family of proteins in the various cells and organisms whose expressions are highly inducible during stress conditions. These proteins participate in protein assembly, trafficking, degradation and therefore play important role in protein turnover. Although the entire functions of each heat shock protein are still not completely investigated, these proteins have been implicated in the processes of protection and repair of stress-induced protein damage. This study has focused on the heat stress related carbonylated proteins, as a marker of oxidative protein modification, in young and senescent fibroblasts. The results are discussed with reference to potential involvement of induced heat shock proteins. This article is part of a Special Issue entitled: Protein Modifications. Biological significance Age-related protein modifications, especially protein carbonylation take a wide place in the literature. In this direction, to highlight the role of heat shock proteins in the oxidative modifications may bring a new aspect to the literature. On the other hand, identified carbonylated proteins in this study confirm the importance of folding process in the mitochondria which will be further analyzed in detail.
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| 10. |
- Jerlström-Hultqvist, Jon, et al.
(författare)
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Hydrogenosomes in the diplomonad Spironucleus salmonicida
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2493-
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Tidskriftsartikel (refereegranskat)abstract
- Acquisition of the mitochondrion is a key event in the evolution of the eukaryotic cell, but diversification of the organelle has occurred during eukaryotic evolution. One example of such mitochondria-related organelles (MROs) are hydrogenosomes, which produce ATP by substrate- level phosphorylation with hydrogen as a byproduct. The diplomonad parasite Giardia intestinalis harbours mitosomes, another type of MRO. Here we identify MROs in the salmon parasite Spironucleus salmonicida with similar protein import and Fe-S cluster assembly machineries as in Giardia mitosomes. We find that hydrogen production is prevalent in the diplomonad genus Spironucleus, and that S. salmonicida MROs contain enzymes characteristic of hydrogenosomes. Evolutionary analyses of known hydrogenosomal components indicate their presence in the diplomonad ancestor, and subsequent loss in Giardia. Our results suggest that hydrogenosomes are metabolic adaptations predating the split between parabasalids and diplomonads, which is deeper than the split between animals and fungi in the eukaryotic tree.
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