| 1. |
- Doverhag, Christina, 1979, et al.
(författare)
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Pharmacological and genetic inhibition of NADPH oxidase does not reduce brain damage in different models of perinatal brain injury in newborn mice
- 2008
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Ingår i: Neurobiology of Disease. - : Elsevier BV. - 1095-953X .- 0969-9961. ; 31:1, s. 133-44
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammation and reactive oxygen species (ROS) are important in the development of perinatal brain injury. The ROS-generating enzyme NADPH oxidase (Nox2) is present in inflammatory cells and contributes to brain injury in adult animal models. HYPOTHESIS: NADPH oxidase contributes to ROS formation and development of injury in the immature brain and inhibition of NADPH oxidase attenuates perinatal brain injury. METHODS: We used animal models of term hypoxia-ischemia (HI) (P9 mice) as well as ibotenate-induced excitotoxic injury (P5 mice) mimicking features of periventricular leukomalacia in preterm infants. In vitro microglia cell cultures were used to investigate NADPH oxidase-dependent ROS formation. In vivo we determined the impact 1) of HI on NADPH oxidase gene expression 2) of genetic (gp91-phox/Nox2 knock-out) and 3) of pharmacological NADPH oxidase inhibition on HI-induced injury and NMDA receptor-mediated excitotoxic injury, respectively. Endpoints were ROS formation, oxidative stress, apoptosis, inflammation and extent of injury. RESULTS: Hypoxia-ischemia increased NADPH oxidase subunits mRNA expression in total brain tissue in vivo. In vitro ibotenate increased NADPH oxidase-dependent formation of reactive oxygen species in microglia. In vivo the inhibition of NADPH oxidase did not reduce the extent of brain injury in any of the animal models. In contrast, the injury was increased by inhibition of NADPH oxidase and genetic inhibition was associated with an increased level of galectin-3 and IL-1beta. CONCLUSION: NADPH oxidase is upregulated after hypoxia-ischemia and activated microglia cells are a possible source of Nox2-derived ROS. In contrast to findings in adult brain, NADPH oxidase does not significantly contribute to the pathogenesis of perinatal brain injury. Results obtained in adult animals cannot be transferred to newborns and inhibition of NADPH oxidase should not be used in attempts to attenuate injury.
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| 2. |
- Hammarlund, Dan, et al.
(författare)
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Late Holocene expansion of Siberian dwarf pine (Pinus pumila) in Kamchatka in response to increased snow cover as inferred from lacustrine oxygen-isotope records
- 2015
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Ingår i: Global and Planetary Change. - : Elsevier BV. - 0921-8181 .- 1872-6364. ; 134:SI, s. 91-100
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Tidskriftsartikel (refereegranskat)abstract
- Holocene records of cellulose-inferred lake-water δ18O were produced from two lake-sediment sequences obtained in central and northern Kamchatka, Russian Far East. The sediment records share similar fluctuations in δ18O during the interval of ca. 5000-800calyr BP that correspond (inversely) with changes in K+ content of the GISP2 ice-core record from Greenland, a proxy for the relative strength of the Siberian High, suggesting control by climate-related variability in δ18O of regional precipitation. The dramatic expansion of Siberian dwarf pine (Pinus pumila) in northern and central Kamchatka between ca. 5000 and 4000calyr BP, as inferred from pollen records from the same and neighbouring sites, appears to have occurred at a time of progressively declining δ18O of precipitation. This development is interpreted as reflecting a regional cooling trend accompanied by increasing winter snowfall related to gradual intensification of the Siberian High from ca. 5000 to ca. 3000calyr BP. A thicker and more long-lasting snow cover can be assumed to have favoured P. pumila by providing a competitive advantage over other boreal and subalpine tree and shrub species in the region during the later part of the Holocene. These results, which are the first of their kind from Kamchatka, provide novel insight into the Holocene vegetational and climatic development in easternmost Asia, as well as long-term atmospheric circulation dynamics in Beringia.
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| 3. |
- Solovieva, N., et al.
(författare)
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The Holocene environmental history of a small coastal lake on the north-eastern Kamchatka Peninsula
- 2015
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Ingår i: Global and Planetary Change. - : Elsevier BV. - 1872-6364 .- 0921-8181. ; 134, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- A radiocarbon and tephra-dated sediment core from Lifebuoy Lake, located on the north-east coast of Kamchatka Peninsula, was analysed for pollen, spores, diatoms, chironomids and tephra in order to uncover regional environmental history. The 6500-year environmental history of Lifebuoy Lake correlates with the broad regional patterns of vegetation development and climate dynamics with both diatoms and chironomids showing near-synchronous changes. Between ca. 6300 and 3900 cal yr BP, the lake ecosystem was naturally enriched, with several Stephanodiscus species dominating the diatom plankton. This natural eutrophication state is likely to be due to a combination of the base-rich catchment geology, the fertilisation effect of several fires in the catchment, silica input from tephra layers and, possibly, nitrogen input from seabirds. The substantial tephra deposit at about 3850 cal yr BP might have stopped sedimentary phosphorus from entering the lake water thus decreasing the trophic state of the lake and facilitating the shift in diatom composition to a benthic Fragiliariaceae complex. Both diatoms and chironomids showed simultaneous compositional changes, which are also reflected by statistically significant changes in their rates of change 300-400 years after the arrival of Pinus pumila in the lake catchment. The rapid increase in both total diatom concentration and the percentage abundance of the large heavy species, Aulacoseira subarctica might be a response to the change in timing and intensity of lake spring turnover due to the changes in the patterns of North Pacific atmospheric circulation, most notably westward shift Of the Aleutian Low. The two highest peaks in A. subarctica abundance at Lifebouy Lake occurred during opposite summer temperature inferences: the earlier peak (3500-2900 cal yr BP) coincided with warm summers and the latter peak (300 cal yr BP-present) occurred during the cold summer period. These imply that A. subarctica shows no direct response to the changes of summer air temperature. Instead, it appears to thrive during the periods of increased winter precipitation, thicker ice and late spring turn-over periods, i.e., shows indirect response to climate. The clearest effect of tephra deposition on the lake ecosystem is above 908 cm (ca. 3800 cal yr BP) where the tephra deposit might have caused the shift from Stephanodiscus-dominated planktonic assemblages to the Fragilariaceae complex of benthic species. Tephra deposits might have also contributed towards the development of eutrophic plankton from about 6300 cal yr BP. It is not certain if several tephra deposits influenced diatom and chironomid changes during the last 300 years. (C) 2015 The Authors. Published by Elsevier B.V.
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| 4. |
- Stefanova, N, et al.
(författare)
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Ultrastructure of alpha-synuclein-positive aggregations in U373 astrocytoma and rat primary glial cells
- 2002
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Ingår i: Neuroscience Letters. - 0304-3940. ; 323:1, s. 37-40
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal alpha-synuclein-positive glial cytoplasmic inclusions are found in Parkinson's disease, multiple system atrophy and dementia with Lewy bodies. We have recently developed an in vitro model of alpha-synuclein-immunoreactive aggregations in U373 astrocytoma cells. We have additionally overexpressed wild-type and a C-terminally truncated form of alpha-synuclein in primary rat glial cells. Astrocytes and oligodendrocytes were found to form alpha-synuclein-positive aggregations in vitro perinuclearly or in the processes of the cells. The morphological studies presented here demonstrate that the aggregations we have observed in vitro are not limited by a membrane but have unclear borders. They have an amorphous dense core that is intensely alpha-synuclein-immunopositive and a predominantly filamentous halo around. Mainly filamentous structures at the border area between the halo and the core are alpha-synuclein-immunoreactive. We conclude that this in vitro model of alpha-synuclein-positive glial aggregations mimics the morphology of the abnormal glial inclusions described in neuroclegenerative disorders and could be a suitable model for studying their role in the pathogenesis of these diseases. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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| 5. |
- Stollenwerk, Maria M, 1959-, et al.
(författare)
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Albumin-based nanoparticles as magnetic resonance contrast agents : I. Concept, first syntheses and characterisation
- 2010
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Ingår i: Histochemistry and Cell Biology. - : Springer. - 0948-6143 .- 1432-119X. ; 133:4, s. 375-404
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Tidskriftsartikel (refereegranskat)abstract
- Abstract To develop a platform for molecular magnetic resonance imaging, we prepared gadolinium-bearing albumin-polylactic acid nanoparticles in the size range 20–40 nm diameter. Iterative cycles of design and testing upscaled the synthesis procedures to gram amounts for physicochemical characterisation and for pharmacokinetic testing. Morphological analyses showed that the nanoparticles were spheroidal with rough surfaces. Particle sizes were measured by direct transmission electron microscopical measurements from negatively contrasted preparations, and by use of photon correlation spectroscopy; the two methods each documented nanoparticle sizes less than 100 nm and generally 10–40 nm diameter, though with significant intrabatch and interbatch variability. The particles’ charge sufficed to hold them in suspension. HSA retained its tertiary structure in the particles. The nanoparticles were stable against turbulent flow conditions and against heat, though not against detergents. MRI imaging of liquid columns was possible at nanoparticle concentrations below 10 mg/ml. The particles were non-cytotoxic, non-thrombogenic and non-immunogenic in a range of assay systems developed for toxicity testing of nanoparticles. They were micellar prior to lyophilisation, but loosely structured aggregated masses after lyophilisation and subsequent resuspension. These nanoparticles provide a platform for further development, based on non-toxic materials of low immunogenicity already in clinical use,not expensive, and synthesized using methods which can be upscaled for industrial production.
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| 6. |
- Väliranta, M, et al.
(författare)
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Plant macrofossil evidence for an early onset of the Holocene summer thermal maximum in northernmost Europe.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Holocene summer temperature reconstructions from northern Europe based on sedimentary pollen records suggest an onset of peak summer warmth around 9,000 years ago. However, pollen-based temperature reconstructions are largely driven by changes in the proportions of tree taxa, and thus the early-Holocene warming signal may be delayed due to the geographical disequilibrium between climate and tree populations. Here we show that quantitative summer-temperature estimates in northern Europe based on macrofossils of aquatic plants are in many cases ca. 2 °C warmer in the early Holocene (11,700-7,500 years ago) than reconstructions based on pollen data. When the lag in potential tree establishment becomes imperceptible in the mid-Holocene (7,500 years ago), the reconstructed temperatures converge at all study sites. We demonstrate that aquatic plant macrofossil records can provide additional and informative insights into early-Holocene temperature evolution in northernmost Europe and suggest further validation of early post-glacial climate development based on multi-proxy data syntheses.
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