| 1. |
- Balk, Lennart, et al.
(författare)
-
Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
|
|
| 2. |
|
|
| 3. |
- Ajayi, Abiodun, et al.
(författare)
-
Altered p53 and NOX1 activity cause bioenergetic defects in a SCA7 polyglutamine disease model
- 2015
-
Ingår i: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1847:4-5, s. 418-428
-
Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxia type 7 (SCA7) is one of the nine neurodegenerative disorders caused by expanded polyglutamine (polyQ) domains. Common pathogenic mechanisms, including bioenergetics defects, have been suggested for these so called polyQ diseases. However, the exact molecular mechanism(s) behind the metabolic dysfunction is still unclear. In this study we identified a previously unreported mechanism, involving disruption of p53 and NADPH oxidase 1 (NOX1) activity, by which the expanded SCA7 disease protein ATXN7 causes metabolic dysregulation. The NOX1 protein is known to promote glycolytic activity, whereas the transcription factor p53 inhibits this process and instead promotes mitochondrial respiration. In a stable inducible PC12 model of SCA7, p53 and mutant ATXN7 co-aggregated and the transcriptional activity of p53 was reduced, resulting in a 50% decrease of key p53 target proteins, like AIF and TIGAR. In contrast, the expression of NOX1 was increased approximately 2 times in SCA7 cells. Together these alterations resulted in a decreased respiratory capacity, an increased reliance on glycolysis for energy production and a subsequent 20% reduction of ATP in SCA7 cells. Restoring p53 function, or suppressing NOX1 activity, both reversed the metabolic dysfunction and ameliorated mutant ATXN7 toxicity. These results hence not only enhance the understanding of the mechanisms causing metabolic dysfunction in SCA7 disease, but also identify NOX1 as a novel potential therapeutic target in SCA7 and possibly other polyQ diseases.
|
|
| 4. |
- Ajayi, Abiodun, et al.
(författare)
-
Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model
- 2012
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common mechanisms of disease pathogenesis suggested for polyQ disorders include aggregation of the polyQ protein and induction of oxidative stress. However, the exact mechanism(s) of toxicity is still unclear. Results: In this study we show that expression of polyQ expanded ATXN7 in a novel stable inducible cell model first results in a concomitant increase in ROS levels and aggregation of the disease protein and later cellular toxicity. The increase in ROS could be completely prevented by inhibition of NADPH oxidase (NOX) complexes suggesting that ATXN7 directly or indirectly causes oxidative stress by increasing superoxide anion production from these complexes. Moreover, we could observe that induction of mutant ATXN7 leads to a decrease in the levels of catalase, a key enzyme in detoxifying hydrogen peroxide produced from dismutation of superoxide anions. This could also contribute to the generation of oxidative stress. Most importantly, we found that treatment with a general anti-oxidant or inhibitors of NOX complexes reduced both the aggregation and toxicity of mutant ATXN7. In contrast, ATXN7 aggregation was aggravated by treatments promoting oxidative stress. Conclusion: Our results demonstrates that oxidative stress contributes to ATXN7 aggregation as well as toxicity and show that anti-oxidants or NOX inhibition can ameliorate mutant ATXN7 toxicity.
|
|
| 5. |
- Ajayi, Abiodun, 1968-
(författare)
-
Molecular mechanism(s) underlying neurodegeneration in SCA7 disease : Role of NOX enzymes and oxidative stress
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide expansion in the SCA7 gene resulting in progressive ataxia and retinal dystrophy. SCA7 belongs to a group of neurodegenerative disorders called polyglutamine (polyQ) diseases, that share the common feature of glutamine tract expansions within otherwise unrelated proteins. Common suggested mechanisms by which polyQ expanded proteins induce toxicity include aggregation and induction of oxidative stress. In this work we examined the connection between oxidative stress, aggregation and toxicity in SCA7 disease. We show that expression of the SCA7 disease protein, ataxin-7 (ATXN7), results in elevated levels of ROS and oxidative stress which in turn lead to toxicity. Our results also revealed that the oxidative stress further contributes to mutant ATXN7 aggregation. Moreover, we show, for the first time, that the major source of the elevated ROS in mutant ATXN7 cells is the increased activation of NOX1 enzymes. Interestingly, our results further revealed that the increased level of NOX1 activity together with altered p53 function leads to a metabolic shift in mutant ATXN7 expressing cells. Treatments with antioxidants, a NOX1 specific inhibitor or NOX1 knock-down, all decreased the ROS level, restored the metabolic shift and ameliorated the mutant ATXN7 induced toxicity. Taken together, we conclude that mutant ATXN7 activate NOX1 enzymes which results in oxidative stress, increased mutant ATXN7 aggregation, metabolic dysfunction and toxicity. NOX1 specific inhibition could thus be a potential therapeutic strategy for SCA7.
|
|
| 6. |
- Ajayi, Abiodun, et al.
(författare)
-
NOX1 and p53 cross-talk in SCA7 polyglutamine toxicity
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expanded polyglutamine repeats. Common toxic gain-of-function mechanisms, including oxidative stress and metabolic dysfunction, have been proposed in these disorders. In a recent study we identified increased activity of the ROS producing NADPH oxidase 1 (NOX1) enzyme and reduced activity of the p53 transcription factor as contributing factors to the oxidative stress and metabolic dysfunction in a SCA7 model. In this study we further investigate the molecular mechanisms behind the altered NOX1 and p53 activity, as well as how these two molecules cross-talk to promote oxidative stress, metabolic dysfunction and toxicity in SCA7. We show that increased NOX1 protein stability, as well as alteration of p53-mediated regulation of NOX1 mRNA levels, contributes to the elevated NOX1 expression in SCA7 cells. Furthermore, we show that the enhance NOX1 activity in SCA7 cells is associated with increased oxidation of p53 and promotes a shift in the p53 sub-cellular localization, as well reduction of soluble p53 levels. Taken together, our results suggest that in SCA7 cells a feed-forward loop between NOX1 and p53 is induced. In this loop NOX1-mediated p53 oxidation results in altered p53 localization and reduced p53 transcriptional activity. In turn, the reduced p53 transcriptional activity promotes the activation of NOX1 mRNA and activity. This loop then contributes to the metabolic dysregulation, oxidative stress and toxicity in SCA7 cells.
|
|
| 7. |
- Ajayi, Abiodun, et al.
(författare)
-
Polyglutamine expanded ataxin-7 alters NOX1 activity and cellular metabolism
- 2013
-
Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common pathogenic mechanisms, including oxidative stress and metabolic dysfunction, have been implicated in polyQ disease. However, the exact toxic mechanism(s) is still unclear. We have previously demonstrated that expression of the SCA7 disease protein, ATXN7, results in oxidative stress and toxicity via activation of ROS-producing NADPH oxidase (NOX) enzymes. In this study, we show that mutant ATXN7 specifically up-regulates and activates the NOX1 family member. Furthermore, we show that the increased NOX1 activity is linked with a metabolic shift, similar to the Warburg effect, and reduced energy levels. Reduction of the NOX1-mediated ROS production reverse the metabolic shift and rescue the ATXN7 induced toxicity. These data suggest that NOX1-mediated metabolic alterations and energy deficit could play a role in SCA7 pathology and possibly in other polyQ diseases.
|
|
| 8. |
- Ajayi, Abiodun
(författare)
-
Study of molecular mechanism(s) underlying neurodegeneration in SCA7 disease : Role of NOX enzymes and oxidative stress
- 2013
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide expansion in the SCA7/ATXN7 gene resulting in progressive ataxia and retinal dystrophy. SCA7 belongs to a group of neurodegenerative disorders called polyglutamine (polyQ) diseases, that share the common feature of glutamine tract expansions within otherwise unrelated proteins. Common suggested mechanisms by which polyQ disorders induce toxicity include aggregation and induction of oxidative stress.In this work, we examined the connection between oxidative stress and toxicity in SCA7 disease. We showed that expression of mutant ataxin-7 (ATXN7) results in elevated level of reactive oxygen species (ROS) and oxidative stress, leading to toxicity. Our results also revealed that the oxidative stress further contributes to mutant ATXN7 aggregation. We showed, for the first time, that the source of the ROS in mutant ATXN7 cells is thorough the activation of the NOX1 enzyme. Interestingly, our results further revealed that the increased level of NOX1 activity and expression by mutant ATXN7 results in a metabolic shift similar to the Warburg effect. Treatments with antioxidants or a NOX1 specific inhibitor decreased the ROS level, restored the metabolic shift and ameliorated the ATXN7 induced toxicity. Taken together, we suggest that mutant ATXN7 specifically activate NOX1 enzyme and that antioxidants treatment or NOX1 specific inhibition could be a potential therapeutic strategy for SCA7.
|
|
| 9. |
- Ajayi, Abiodun, et al.
(författare)
-
The role of NADPH oxidase (NOX) enzymes in neurodegenerative disease
- 2013
-
Ingår i: Frontiers in Biology. - : Springer Science and Business Media LLC. - 1674-7992 .- 1674-7984. ; 8:2, s. 175-188
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, mounting evidence implicating reactive oxygen species (ROS) generated by NADPH oxidase(NOX) enzymes in the pathogenesis of several neurodegenerative diseases including Amyotrophic lateral sclerosis(ALS), Alzheimer’s (AD), Parkinson’s (PD) and polyglutamine disease, have arisen. NOX enzymes are transmembraneproteins and generate reactive oxygen species by transporting electrons across lipid membranes. Under normal healthyconditions, low levels of ROS produced by NOX enzymes have been shown to play a role in neuronal differentiation andsynaptic plasticity. However, in chronic neurodegenerative diseases over-activation of NOX in neurons, as well as inastrocytes and microglia, has been linked to pathogenic processes such as oxidative stress, exitotoxicity andneuroinflammation. In this review, we summarize the current knowledge about NOX functions in the healthy centralnervous system and especially the role of NOX enzymes in neurodegenerative disease processes.
|
|
| 10. |
- Albæk, Karsten, et al.
(författare)
-
Bedre sent enn aldri? Hvordan sen fullføring av videregående skole påvirker tidlig karriere
- 2020
-
Ingår i: Søkelys på arbeidslivet. - : Scandinavian University Press / Universitetsforlaget AS. - 1504-8004 .- 1504-7989. ; 37:1-2, s. 124-141
-
Tidskriftsartikel (refereegranskat)abstract
- Får ungdom i Norden som fullfører videregående skole mellom 21 og 28 års alder bedre tilgang til arbeidsmarkedetenn de som ikke har fullført ved 28? Vi finner at de som har fullført innen 28 års alder, har 12-15 prosentpoeng laveresannsynlighet for å være NEET (Not in Employment, Education or Training) enn de som ikke har fullført. Når vikontrollerer for sosioøkonomisk bakgrunn og særlig for tidlige skole-til-arbeid overganger mellom 16 og 20 år for-svinner mye av forskjellene mellom land, men fortsatt gjenstår de fleste av forskjellene mellom de som fullfører sentog de som ikke fullfører.
|
|
| 11. |
- Albæk, Karsten, et al.
(författare)
-
Better Late Than Never? How Late Completion Affects the Early Careers of Dropouts
- 2019
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Across the OECD countries, dropouts from upper secondary schooling fare worse in the labor market, with higher NEET rates more spells of unemployment and lower earnings. Among the dropouts, there are however significant shares who complete at a later age. In this paper, we thus ask the question: Does it pay for young adults who do not complete upper secondary schooling by the age of 21, to do so at some point during the subsequent 7 years, that is, before turning 28? In all four Nordic countries under scrutiny, we find that late completion lowers the probability of being outside employment, education or training (NEET) at age 28. Moreover, the exact age of completion does not seem to matter. Our estimates are robust to the inclusion of extensive controls for socioeconomic background and early schooling paths, and similar to the ones produced by event history analysis with individual fixed effects. This indicates that late completion of upper secondary schooling plays an important role for the labor market inclusion of young dropouts.
|
|
| 12. |
- Allesson, Lina, et al.
(författare)
-
Impact of photo-chemical processing of DOC on the bacterioplankton respiratory quotient in aquatic ecosystems
- 2016
-
Ingår i: Geophysical Research Letters. - 1944-8007. ; 43:14, s. 7538-7545
-
Tidskriftsartikel (refereegranskat)abstract
- Many studies assume a respiratory quotient (RQ = molar ratio of CO2 produced to O2 consumed) close to 1 when calculating bacterioplankton respiration. However, evidence suggests that RQ depends on the chemical composition of the respired substrate pool that may be altered by photo-chemical production of oxygen-rich substrates, resulting in elevated RQs. Here we conducted a novel study of the impact of photo-chemical processing of dissolved organic carbon (DOC) on RQ. We monitored the bacterial RQ in bioassays of both ultraviolet light irradiated and non-irradiated humic lake water, using optic gas-pressure sensors. In the experimentally irradiated samples the average RQ value was significantly higher (3.4-3.5 [± 0.4 s.e.]) than that in the dark controls (1.3 [± 0.1 s.e.]). Our results show that the RQ is systematically higher than 1 when the bacterial metabolism in large part is based on photo-products. By assuming an RQ of 1, bacterioplankton respiration in freshwater ecosystems may be greatly underestimated.
|
|
| 13. |
- Andresen, Louise C., et al.
(författare)
-
Seasonal changes in nitrogen availability, and root and microbial uptake of (15)N(13)C(9)-phenylalanine and (15)N-ammonium in situ at a temperate heath
- 2011
-
Ingår i: Applied Soil Ecology. - : Elsevier BV. - 0929-1393. ; 51, s. 94-101
-
Tidskriftsartikel (refereegranskat)abstract
- In the plant biosynthesis of secondary compounds, phenylalanine is a precursor of condensed tannins. Tannins are deposited into the soil in plant root exudates and dead plant material and have been suggested to precipitate some soil nutrients and hence reduce nutrient availability for plants. Free amino acid, inorganic and microbial N concentration during the growing season was investigated in an ecosystem with a natural tannin chemosphere. The influence of tannins on the uptake of nitrogen in plants and microbes was followed by injecting tannic acid (TA), ammonium-(15)N and phenylalanine-(15)N/(13)C(9). Plants preferred ammonium over phenylalanine, while microbes had no preference. Soil microbes had a 77% uptake of intact phenylalanine. Phenylalanine was acquired intact by both grasses and Calluna, with 63% and 38% uptake of intact phenylalanine in grass fine roots and Calluna roots, respectively. Inorganic N and amino acid concentrations were lowest in the period with highest plant activity and grass root biomass but were unaffected by TA addition. (C) 2011 Elsevier B.V. All rights reserved.
|
|
| 14. |
- Andresen, Louise C., et al.
(författare)
-
Uptake of pulse injected nitrogen by soil microbes and mycorrhizal and non-mycorrhizal plants in a species-diverse subarctic heath ecosystem
- 2008
-
Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 313:1-2, s. 283-295
-
Tidskriftsartikel (refereegranskat)abstract
- N-15 labeled ammonium, glycine or glutamic acid was injected into subarctic heath soil in situ, with the purpose of investigating how the nitrogen added in these pulses was subsequently utilized and cycled in the ecosystem. We analyzed the acquisition of N-15 label in mycorrhizal and non-mycorrhizal plants and in soil microorganisms, in order to reveal probable differences in acquisition patterns between the two functional plant types and between plants and soil microorganisms. Three weeks after the label addition, with the N-15-forms added with same amount of nitrogen per square meter, we analyzed the N-15-enrichment in total soil, in soil K2SO4 (0.5 M) extracts and in the microbial biomass after vacuum-incubation of soil in chloroform and subsequent K2SO4 extraction. Furthermore the N-15-enrichment was analyzed in current years leaves of the dominant plant species sampled three, five and 21 days after label addition. The soil microorganisms had very high N-15 recovery from all the N sources compared to plants. Microorganisms incorporated most N-15 from the glutamic acid source, intermediate amounts of N-15 from the glycine source and least N-15 from the NH4+ source. In contrast to microorganisms, all ten investigated plant species generally acquired more N-15 label from the NH4+ source than from the amino acid sources. Non-mycorrhizal plant species showed higher concentration of N-15 label than mycorrhizal plant species 3 days after labeling, while 21 days after labeling their acquisition of N-15 label from amino acid injection was lower than, and the acquisition of N-15 label from NH4 injection was similar to that of the mycorrhizal species. We conclude that the soil microorganisms were more efficient than plants in acquiring pulses of nutrients which, under natural conditions, occur after e. g. freeze-thaw and dry rewet events, although of smaller size. It also appears that the mycorrhizal plants in the short term may be less efficient than non-mycorrhizal plants in nitrogen acquisition, but in a longer term show larger nitrogen acquisition than non-mycorrhizal plants. However, the differences in N-15 uptake patterns may also be due to differences in leaf longevity and woodiness between plant functional groups.
|
|
| 15. |
- Berggren, Martin, 1981-, et al.
(författare)
-
Efficient aquatic bacterial metabolism of dissolved low-molecular-weight compounds from terrestrial sources
- 2010
-
Ingår i: The ISME Journal. - London : Nature Publishing Group. - 1751-7362 .- 1751-7370. ; 4:3, s. 408-416
-
Tidskriftsartikel (refereegranskat)abstract
- Carboxylic acids (CAs), amino acids (AAs) and carbohydrates (CHs) in dissolved free forms can be readily assimilated by aquatic bacteria and metabolized at high growth efficiencies. Previous studies have shown that these low-molecular-weight (LMW) substrates are released by phytoplankton but also that unidentified LMW compounds of terrestrial origin is a subsidy for bacterial metabolism in unproductive freshwater systems. We tested the hypothesis that different terrestrially derived CA, AA and CH compounds can offer substantial support for aquatic bacterial metabolism in fresh waters that are dominated by allochthonous dissolved organic matter (DOM). Drainage water from three catchments of different characters in the Krycklan experimental area in Northern Sweden were studied at the rising and falling limb of the spring flood, using a 2-week bioassay approach. A variety of CA, AA and CH compounds were significantly assimilated by bacteria, meeting 15–100% of the bacterial carbon demand and explaining most of the observed variation in bacterial growth efficiency (BGE; R2=0.66). Of the 29 chemical species that was detected, acetate was the most important, representing 45% of the total bacterial consumption of all LMW compounds. We suggest that LMW organic compounds in boreal spring flood drainage could potentially support all in situ bacterial production in receiving lake waters during periods of weeks to months after the spring flood.
|
|
| 16. |
- Berggren, Martin, et al.
(författare)
-
Lake secondary production fueled by rapid transfer of low molecular weight organic carbon from terrestrial sources to aquatic consumers
- 2010
-
Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 13:7, s. 870-880
-
Tidskriftsartikel (refereegranskat)abstract
- P>Carbon of terrestrial origin often makes up a significant share of consumer biomass in unproductive lake ecosystems. However, the mechanisms for terrestrial support of lake secondary production are largely unclear. By using a modelling approach, we show that terrestrial export of dissolved labile low molecular weight carbon (LMWC) compounds supported 80% (34-95%), 54% (19-90%) and 23% (7-45%) of the secondary production by bacteria, protozoa and metazoa, respectively, in a 7-km2 boreal lake (conservative to liberal estimates in brackets). Bacterial growth on LMWC was of similar magnitude as that of primary production (PP), and grazing on bacteria effectively channelled the LMWC carbon to higher trophic levels. We suggest that rapid turnover of forest LMWC pools enables continuous export of fresh photosynthates and other labile metabolites to aquatic systems, and that substantial transfer of LMWC from terrestrial sources to lake consumers can occur within a few days. Sequestration of LMWC of terrestrial origin, thus, helps explain high shares of terrestrial carbon in lake organisms and implies that lake food webs can be closely dependent on recent terrestrial PP.
|
|
| 17. |
- Berggren, Martin, et al.
(författare)
-
Quality transformation of dissolved organic carbon during water transit through lakes : contrasting controls by photochemical and biological processes
- 2018
-
Ingår i: Biogeosciences. - : European Geosciences Union (EGU). - 1726-4170 .- 1726-4189. ; 15:2, s. 457-470
-
Tidskriftsartikel (refereegranskat)abstract
- Dissolved organic carbon (DOC) may be removed, transformed, or added during water transit through lakes, resulting in changes in DOC composition and pigmentation (color). However, the process-based understanding of these changes is incomplete, especially for headwater lakes. We hypothesized that because heterotrophic bacteria preferentially consume noncolored DOC, while photochemical processing removes colored fractions, the overall changes in DOC color upon water passage through a lake depend on the relative importance of these two processes, accordingly. To test this hypothesis we combined laboratory experiments with field studies in nine boreal lakes, assessing both the relative importance of different DOC decay processes (biological or photochemical) and the loss of color during water transit time (WTT) through the lakes. We found that influence from photo-decay dominated changes in DOC quality in the epilimnia of relatively clear headwater lakes, resulting in systematic and selective net losses of colored DOC. However, in highly pigmented brown-water lakes (absorbance at 420 nm > 7 m(-1)) biological processes dominated, and there was no systematic relationship between color loss and WTT. Moreover, in situ data and dark experiments supported our hypothesis on the selective microbial removal of nonpigmented DOC, mainly of low molecular weight, leading to persistent water color in these highly colored lakes. Our study shows that brown headwater lakes may not conform to the commonly reported pattern of the selective removal of colored constituents in freshwaters, as DOC can show a sustained degree of pigmentation upon transit through these lakes.
|
|
| 18. |
- Bergqvist, Cecilia, et al.
(författare)
-
Monitoring of chromatin organization in live cells by FRIC. Effects of the inner nuclear membrane protein Samp1
- 2019
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 47:9
-
Tidskriftsartikel (refereegranskat)abstract
- In most cells, transcriptionally inactive heterochromatin is preferentially localized in the nuclear periphery and transcriptionally active euchromatin is localized in the nuclear interior. Different cell types display characteristic chromatin distribution patterns, which change dramatically during cell differentiation, proliferation, senescence and different pathological conditions. Chromatin organization has been extensively studied on a cell population level, but there is a need to understand dynamic reorganization of chromatin at the single cell level, especially in live cells. We have developed a novel image analysis tool that we term Fluorescence Ratiometric Imaging of Chromatin (FRIC) to quantitatively monitor dynamic spatiotemporal distribution of euchromatin and total chromatin in live cells. A vector (pTandemH) assures stoichiometrically constant expression of the histone variants Histone 3.3 and Histone 2B, fused to EGFP and mCherry, respectively. Quantitative ratiometric (H3.3/H2B) imaging displayed a concentrated distribution of heterochromatin in the periphery of U2OS cell nuclei. As proof of concept, peripheral heterochromatin responded to experimental manipulation of histone acetylation. We also found that peripheral heterochromatin depended on the levels of the inner nuclear membrane protein Samp1, suggesting an important role in promoting peripheral heterochromatin. Taken together, FRIC is a powerful and robust new tool to study dynamic chromatin redistribution in live cells.
|
|
| 19. |
- Bruun, Hans Henrik, et al.
(författare)
-
Exudation of low molecular weight organic acids by germinating seeds of two edaphic ecotypes of Silene nutans L.
- 2001
-
Ingår i: Acta Oecologica. - 1146-609X. ; 22:5-6, s. 285-291
-
Tidskriftsartikel (refereegranskat)abstract
- Two parapatric ecotypes of Silene nutans, exhibiting distinct allozyme patterns, morphology and autecology were investigated for differences in exudation of low molecular weight organic acids from germinating seeds, and for differences in seed phosphorus content. The calcicolous ecotype is restricted to calcareous soils, and the silicicolous one predominantly occurs on acid soils, and sometimes, although less frequently, on neutral to alkaline soils. No clear difference was found between ecotypes. However, within the silicicolous ecotype seed samples showed marked differences in exudation pattern and seed phosphorus content depending on origin along the soil acidity gradient. Seeds of low-pH origin exuded more dicarboxylic acids (malic + succinic acid, oxalic acid) and had a lower phosphorus content than seeds of high pH origin. The exudation of dicarboxylic acids from seeds of low pH origin is probably an adaptation to adverse conditions (aluminium toxicity) on acid soils. The pattern is similar to that found among different cultivars of wheat. It is contrasted to the pattern found on comparison of a suite of calcifugous and calcicolous species, where exudation of di- and tricarboxylic acids is associated with solubilisation of recalcitrantly bound phosphorus and iron in calcareous soils. (C) 2001 Editions scientifiques et medicales Elsevier SAS.
|
|
| 20. |
|
|
| 21. |
- Christensen, Torben, et al.
(författare)
-
A catchment-scale carbon and greenhouse gas budget of a subartic landscape
- 2007
-
Ingår i: Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Science. - : The Royal Society. - 1364-503X .- 1471-2962. ; 365:1856, s. 1643-1656
-
Tidskriftsartikel (refereegranskat)abstract
- This is the first attempt to budget average current annual carbon (C) and associated greenhouse gas (GHG) exchanges and transfers in a subarctic landscape, the Lake Torneträsk catchment in northern Sweden. This is a heterogeneous area consisting of almost 4000 km2 of mixed heath, birch and pine forest, and mires, lakes and alpine ecosystems. The magnitudes of atmospheric exchange of carbon in the form of the GHGs, CO2 and CH4 in these various ecosystems differ significantly, ranging from little or no flux in barren ecosystems over a small CO2 sink function and low rates of CH4 exchange in the heaths to significant CO2 uptake in the forests and also large emissions of CH4 from the mires and small lakes. The overall catchment budget, given the size distribution of the individual ecosystem types and a first approximation of run-off as dissolved organic carbon, reveals a landscape currently with a significant sink capacity for atmospheric CO2. This sink capacity is, however, extremely sensitive to environmental changes, particularly those that affect the birch forest ecosystem. Climatic drying or wetting and episodic events such as insect outbreaks may cause significant changes in the sink function. Changes in the sources of CH4 through increased permafrost melting may also easily change the sign of the current radiative forcing, due to the stronger impact per gram of CH4 relative to CO2. Hence, to access impacts on climate, the atmospheric C balance alone has to be weighed in a radiative forcing perspective. When considering the emissions of CH4 from the mires and lakes as CO2 equivalents, the Torneträsk catchment is currently a smaller sink of radiative forcing, but it can still be estimated as representing the equivalent of approximately 14 000 average Swedish inhabitants' emissions of CO2. This can be compared with the carbon emissions of less than 200 people who live permanently in the catchment, although this comparison disregards substantial emissions from the non-Swedish tourism and transportation activities.
|
|
| 22. |
- Christensen, Torben, et al.
(författare)
-
Factors controlling large scale variations in methane emissions from wetlands
- 2003
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 30:7
-
Tidskriftsartikel (refereegranskat)abstract
- [1] Global wetlands are, at estimate ranging 115-237 Tg CH4/yr, the largest single atmospheric source of the greenhouse gas methane (CH4). We present a dataset on CH4 flux rates totaling 12 measurement years at sites from Greenland, Iceland, Scandinavia and Siberia. We find that temperature and microbial substrate availability (expressed as the organic acid concentration in peat water) combined explain almost 100% of the variations in mean annual CH4 emissions. The temperature sensitivity of the CH4 emissions shown suggests a feedback mechanism on climate change that could validate incorporation in further developments of global circulation models.
|
|
| 23. |
- Christensen, Torben R., et al.
(författare)
-
Large scale variations in CH4 emissions from wetlands explained by temperature and substrate availability
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Globally, wetlands are at estimates ranging 115-237 Tg C4/yr1 the largest single source of the greenhouse gas CH4 to the atmosphere. Important feedback mechanisms on climate change arising from changing exchanges of C02 between the terrestrial biosphere and the atmosphere have recently been identified2. A related question is how will possible changes in the CH4 emissions from wetlands affect the further development of the greenhouse effect? Here we show using comparable methods in a wide range of wetlands ranging from Greenland to Siberia that regardless the dependency on soil moisture, plant productivity and other factors, temperature is the strongest control and predictor of CH4 emissions across both temporal and large spatial scales. Furthermore, we show that CH4 flux variations not explained by temperature can beattributed to differences in microbial substrate availability (expressed as the organic acid concentration in peat water). Combined, soil temperature and organic acid concentrations explains 99% of the variation in CH4 fluxes between the different sites. The temperature sensitivity of the CH4 emissions shown suggests a strong feedback mechanism on climatechange that should valid incorporation in developments of global circulation models.
|
|
| 24. |
- Dahlberg, Carin I. M., et al.
(författare)
-
A Novel Mouse Model for the Hyper-IgM Syndrome : A Spontaneous Activation-Induced Cytidine Deaminase Mutation Leading to Complete Loss of Ig Class Switching and Reduced Somatic Hypermutation
- 2014
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 193:9, s. 4732-4738
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a spontaneously derived mouse line that completely failed to induce Ig class switching in vitro and in vivo. The mice inherited abolished IgG serum titers in a recessive manner caused by a spontaneous G -> A transition mutation in codon 112 of the aicda gene, leading to an arginine to histidine replacement (AID(R112H)). Ig class switching was completely reconstituted by expressing wild-type AID. Mice homozygous for AID(R112H) had peripheral B cell hyperplasia and large germinal centers in the absence of Ag challenge. Immunization with SRBCs elicited an Ag-specific IgG1 response in wild-type mice, whereas AID(R112H) mice failed to produce IgG1 and had reduced somatic hypermutation. The phenotype recapitulates the human hyper-IgM (HIGM) syndrome that is caused by point mutations in the orthologous gene in humans, and the AID(R112H) mutation is frequently found in HIGM patients. The AID(R112H) mouse model for HIGM provides a powerful and more precise tool than conventional knockout strategies.
|
|
| 25. |
- Ekstrand, Carl, et al.
(författare)
-
Plasma atropine concentrations associated with decreased intestinal motility in horses
- 2022
-
Ingår i: Frontiers in Veterinary Science. - : Frontiers Media S.A.. - 2297-1769. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionAtropine is an essential part of the treatment protocol for equine uveitis. Topical atropine administration has been associated with decreased intestinal motility and abdominal pain in horses. Experimental studies have indicated that frequent dosing is associated with a higher risk than dosing every 6 h. Unfortunately, no quantitative pharmacodynamic data for inhibition of the equine gut are published. Materials and methodsEight standardbred horses were assigned to receive either atropine or saline (control) to be infused over 30 min in a two-treatment cross-over design. Atropine concentrations in plasma were measured using ultra-high-performance liquid chromatography-tandem mass spectrometry. Intestinal motility was measured using borborygmi frequency and electrointestinography (EIG). Experimental data were analyzed using a non-linear mixed effects model. The model was then used to simulate different dosing regimens. ResultsAtropine significantly decreased borborygmi response and EIG response. Six horses developed clinical signs of abdominal pain. The pharmacokinetic typical values were 0.31, 1.38, 0.69, and 1.95 L/kg center dot h for the volumes of the central, the highly perfused, the scarcely perfused compartments, and the total body clearance, respectively. The pharmacodynamic typical values were 0.31 mu g/L and 0.6 and 207 nV(2)7 cpm for the plasma concentration at 50% of the maximum response and the maximum response and the baseline of cecal EIG response, respectively. Six different dosing regimens of topical atropine sulfate to the eye (0.4 and 1 mg every hour, every 3 h, and every 6 h) were simulated. ConclusionThe IV PK/PD data coupled with simulations predict that administration of 1 mg of topical atropine sulfate administered to the eye every hour or every 3 h will lead to atropine accumulation in plasma and decreased intestinal myoelectric activity. Administration every 6 h predicted a safe dosing regimen in full-sized horses. Clinical studies would be valuable to confirm the conclusions. For smaller equids and horses put at risk for colic due to othercauses, droplet bottles that deliver 40 mu l of 1% atropine sulfate per drop or less may be used to lower the risk further.
|
|
