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- Celojevic, Dragana, 1985, et al.
(författare)
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Genetic Variation of Superoxide Dismutases in Patients with Primary Open-angle Glaucoma
- 2014
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Ingår i: Ophthalmic Genetics. - : Informa UK Limited. - 1381-6810 .- 1744-5094. ; 35:2, s. 79-84
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: Oxidative stress has been described as an underlying pathogenetic mechanism in retinal ganglion cell apoptosis, which is a hallmark of primary open-angle glaucoma (POAG). Superoxide dismutases (SODs) are enzymes involved in the protection against oxidative stress by detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in the copper-zinc-containing SOD1 and SOD3, and in the manganese superoxide dismutase SOD2, in POAG patients. Methods: The study included 239 patients with POAG and 185 controls, all of Estonian origin, recruited at two ophthalmic clinics in Tartu, Estonia. Eleven SNPs, either functional, disease-associated or tag SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. Results: Using binary logistic regression in an additive model, the rs2842980 SNP in SOD2 was significantly associated with POAG diagnosis (p=0.03) at a univariate level. None of the studied SNPs showed an association with risk of POAG in a multivariate analysis, including age and current smoking as covariates. Analysis of SOD2 haplotypes did not show any association with risk of POAG. Conclusions: If oxidative stress is an important mechanism in POAG-related retinal ganglion cell death, genetic variations in SOD1, SOD2 and SOD3 are not major contributors in the pathogenesis.
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| 3. |
- Celojevic, Dragana, 1985, et al.
(författare)
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Superoxide dismutase gene polymorphisms in patients with age-related cataract
- 2013
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 34:3, s. 140-145
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract. MATERIALS AND METHODS: The study included an Estonian sample of 492 patients with age-related cataract, subgrouped into nuclear, cortical, posterior subcapsular and mixed cataract, and 185 controls. Twelve SNPs in SOD1, SOD2 and SOD3 were genotyped using TaqMan Allelic Discrimination. Haplotype analysis was performed on the SNPs in SOD2. RESULTS: None of the studied SNPs showed an association with risk of cataract. These results were consistent after adding known risk factors (age, sex and smoking) as covariates in the multivariate analyses and after stratification by cataract subtype. Analysis of SOD2 haplotypes did not show any associations with risk of cataract. CONCLUSIONS: If genetic variation in genes encoding SOD-1, SOD-2 and SOD-3 contributes to cataract formation, there is no major contribution of the SNPs analyzed in the present study.
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| 6. |
- Garcia-Martinez, Fernando, et al.
(författare)
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Reduced Carbon Monoxide Saturation Coverage on Vicinal Palladium Surfaces: The Importance of the Adsorption Site
- 2021
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 12:39, s. 9508-9515
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Tidskriftsartikel (refereegranskat)abstract
- Steps at metal surfaces may influence energetics and kinetics of catalytic reactions in unexpected ways. Here, we report a significant reduction of the CO saturation coverage in Pd vicinal surfaces, which in turn is relevant for the light-off of the CO oxidation reaction. The study is based on a systematic investigation of CO adsorption on vicinal Pd(111) surfaces making use of a curved Pd crystal. A combined X-ray Photoelectron Spectroscopy and DFT analysis allows us to demonstrate that an entire row of atomic sites under Pd steps remains free of CO upon saturation at 300 K, leading to a step-density-dependent reduction of CO coverage that correlates with the observed decrease of the light-off temperature during CO oxidation in vicinal Pd surfaces.
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| 7. |
- Abb, Marcel J.S., et al.
(författare)
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Thermal Stability of Single-Crystalline IrO2(110) Layers : Spectroscopic and Adsorption Studies
- 2020
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 124:28, s. 15324-15336
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of ultrathin single-crystalline IrO2(110) films with the gas phase proceeds via the coordinatively unsaturated sites (cus), in particular Ircus, the undercoordinated oxygen species on-top O (Oot) that are coordinated to Ircus, and bridging O (Obr). With the combination of different experimental techniques, such as thermal desorption spectroscopy, scanning tunneling microscopy (STM), high-resolution core-level spectroscopy (HRCLS), infrared spectroscopy, and first-principles studies employing density functional theory calculations, we are able to elucidate surface properties of single-crystalline IrO2(110). We provide spectroscopic fingerprints of the active surface sites of IrO2(110). The freshly prepared IrO2(110) surface is virtually inactive toward gas-phase molecules. The IrO2(110) surface needs to be activated by annealing to 500-600 K under ultrahigh vacuum (UHV) conditions. In the activation step, Ircus sites are liberated from on-top oxygen (Oot) and monoatomic Ir metal islands are formed on the surface, leading to the formation of a bifunctional model catalyst. Vacant Ircus sites of IrO2(110) allow for strong interaction and accommodation of molecules from the gas phase. For instance, CO can adsorb atop on Ircus and water forms a strongly bound water layer on the activated IrO2(110) surface. Single-crystalline IrO2(110) is thermally not very stable although chemically stable. Chemical reduction of IrO2(110) by extensive CO exposure at 473 K is not observed, which is in contrast to the prototypical RuO2(110) system.
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| 8. |
- Michno, Wojciech, 1992, et al.
(författare)
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GM1 locates to mature amyloid structures implicating a prominent role for glycolipid-protein interactions in Alzheimer pathology
- 2019
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Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1878-1454 .- 1570-9639. ; 1867:5, s. 458-467
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Tidskriftsartikel (refereegranskat)abstract
- While the molecular mechanisms underlying Alzheimer's disease (AD) remain largely unknown, abnormal accumulation and deposition of beta amyloid (AD) peptides into plaques has been proposed as a critical pathological process driving disease progression. Over the last years, neuronal lipid species have been implicated in biological mechanisms underlying amyloid plaque pathology. While these processes comprise genetic features along with lipid signaling as well as direct chemical interaction of lipid species with A beta mono- and oligomers, more efforts are needed to spatially delineate the exact lipid-A beta plaque interactions in the brain. Chemical imaging using mass spectrometry (MS) allows to probe the spatial distribution of lipids and peptides in complex biological tissues comprehensively and at high molecular specificity. As different imaging mass spectrometry (IMS) modalities provide comprehensive molecular and spatial information, we here describe a multimodal ToF-SIMS- and MALDI-based IMS strategy for probing lipid and A beta peptide changes in a transgenic mouse model of AD (tgAPP(ArcSwe)). Both techniques identified a general AD-associated depletion of cortical sulfatides, while multimodal MALDI IMS revealed plaque specific lipid as well as A beta peptide isoforms. In addition, MALDI IMS analysis revealed chemical features associated with morphological heterogeneity of individual A beta deposits. Here, an altered GM1 to GM2/GM3 ganglioside metabolism was observed in the diffuse periphery of plaques but not in the core region. This was accompanied by an enrichment of A beta 1-40arc peptide at the core of these deposits. Finally, a localization of arachidonic acid (AA) conjugated phosphatidylinositols (PI) and their corresponding degradation product, lysophosphatidylinositols (LPI) to the periphery of A beta plaques was observed, indicating site specific macrophage activation and ganglioside processing.
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| 9. |
- Michno, Wojciech, 1992, et al.
(författare)
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Molecular imaging mass spectrometry for probing protein dynamics in neurodegenerative disease pathology
- 2019
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 151:4, s. 488-506
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Forskningsöversikt (refereegranskat)abstract
- Recent advances in the understanding of basic pathological mechanisms in various neurological diseases depend directly on the development of novel bioanalytical technologies that allow sensitive and specific chemical imaging at high resolution in cells and tissues. Mass spectrometry-based molecular imaging (IMS) has gained increasing popularity in biomedical research for mapping the spatial distribution of molecular species in situ. The technology allows for comprehensive, untargeted delineation of in situ distribution profiles of metabolites, lipids, peptides and proteins. A major advantage of IMS over conventional histochemical techniques is its superior molecular specificity. Imaging mass spectrometry has therefore great potential for probing molecular regulations in CNS-derived tissues and cells for understanding neurodegenerative disease mechanism. The goal of this review is to familiarize the reader with the experimental workflow, instrumental developments and methodological challenges as well as to give a concise overview of the major advances and recent developments and applications of IMS-based protein and peptide profiling with particular focus on neurodegenerative diseases. This article is part of the Special Issue “Proteomics”. (Figure presented.).
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| 10. |
- Sandin, Linnea, et al.
(författare)
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Beneficial effects of increased lysozyme levels in Alzheimer’s disease modelled in Drosophila melanogaster
- 2016
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 283:19, s. 3508-3522
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Tidskriftsartikel (refereegranskat)abstract
- Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer’s disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD.
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