| 1. |
- Ekblad, Alf, 1957-, et al.
(författare)
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The production and turnover of extramatrical mycelium of ectomycorrhizal fungi in forest soils : role in carbon cycling
- 2013
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Ingår i: Plant and Soil. - : Springer Science and Business Media LLC. - 0032-079X .- 1573-5036. ; 366:1-2, s. 1-27
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Forskningsöversikt (refereegranskat)abstract
- There is growing evidence of the importance of extramatrical mycelium (EMM) of mycorrhizal fungi in carbon (C) cycling in ecosystems. However, our understanding has until recently been mainly based on laboratory experiments, and knowledge of such basic parameters as variations in mycelial production, standing biomass and turnover as well as the regulatory mechanisms behind such variations in forest soils is limited. Presently, the production of EMM by ectomycorrhizal (EM) fungi has been estimated at similar to 140 different forest sites to be up to several hundreds of kg per ha per year, but the published data are biased towards Picea abies in Scandinavia. Little is known about the standing biomass and turnover of EMM in other systems, and its influence on the C stored or lost from soils. Here, focussing on ectomycorrhizas, we discuss the factors that regulate the production and turnover of EMM and its role in soil C dynamics, identifying important gaps in this knowledge. C availability seems to be the key factor determining EMM production and possibly its standing biomass in forests but direct effects of mineral nutrient availability on the EMM can be important. There is great uncertainty about the rate of turnover of EMM. There is increasing evidence that residues of EM fungi play a major role in the formation of stable N and C in SOM, which highlights the need to include mycorrhizal effects in models of global soil C stores.
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| 2. |
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| 3. |
- Andersson, C David, et al.
(författare)
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Discovery of Ligands for ADP-Ribosyltransferases via Docking-Based Virtual Screening
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:17, s. 7706-7718
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Tidskriftsartikel (refereegranskat)abstract
- The diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are an enzyme family that catalyses the transfer of ADP-ribose units onto substrate proteins, using nicotinamide adenine dinucleotide (NAD(+)) as a co-substrate. They have a documented role in chromatin remodelling and DNA repair; and inhibitors of ARTD1 and 2 (PARP1 and 2) are currently in clinical trials for the treatment of cancer. The detailed function of most other ARTDs is still unknown. Using virtual screening we identified small ligands of ARTD7 (PARP15/BAL3) and ARTD8 (PARP14/BAL2). Thermal-shift assays confirmed that 16 compounds, belonging to eight structural classes, bound to ARTD7/ARTD8. Affinity measurements with isothermal titration calorimetry for two isomers of the most promising hit compound confirmed binding in the low micromolar range to ARTD8. Crystal structures showed anchoring of the hits in the nicotinamide pocket. These results form a starting point in the development of chemical tools for the study of the role and function of ARTD7 and ARTD8.
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| 4. |
- Björk, Robert G., 1974, et al.
(författare)
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Climate-related soil changes in tundra ecosystems at Latnjajaure, northern Sweden – an ITEX-IPY project
- 2010
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Ingår i: International Polar Year Oslo Science Conference.
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Konferensbidrag (refereegranskat)abstract
- During the 90'ies, the International Tundra Experiment (ITEX) was established as a leading project in arctic and alpine ecology, and has become a model for many later network establishments. The present study capitalizes on the early efforts of ITEX and aims at assessing ecosystem changes in the alpine areas of northern Sweden above timberline, i.e. the tundra, in relation to global change. By using the "old" ITEX plots established during the early years of the program we have measured ecosystem respiration (ER), the Normalized Difference Vegetation Index, and nitrogen (N) mineralization over the growing season. In addition, have soil samples been taken to quantify changes in the carbon (C) and N pool, including 13C and 15N. After 12 to 15 years of open top chamber (OTC) treatment no statistical effect was found on the soil temperature (10 cm soil depth), although the was an overall increase in all OTC by +0.2°C. However, the soil moisture decreased significantly by 3-14%, depending on plant community, in the OTCs compared to ambient conditions. Preliminary, there was a 20-37% non-significant higher mean ER in the OTC compared to the ambient plots over the growing season. Furthermore, the OTC treatment did not affect the growing season mineralization of inorganic N, or total C and N content of the soil. The stable isotope data showed both enrichment and depletion as a consequence of the OTC treatment, but no general pattern was discerned. Thus, this non-significant higher ER is most likely of plant origin than soil, as the plant standing biomass has increased in the OTCs. This study does not support the current consensus that tundra soils will alter their C and N dynamics in response to climate change.
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| 5. |
- Björk, Robert G., 1974, et al.
(författare)
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Long-term warming effects on carbon and nitrogen dynamics in tundra soils
- 2012
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Ingår i: 20th Anniversary ITEX Workshop, El Paso, USA, 17–21 January 2012.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- During IPY 2008 we used the ITEX experiment in Latnjajaure (northern Sweden), established during the early years of the program, to investigate long-term warming effects on ecosystem respiration (ER), carbon (C) and nitrogen (N) pool (including d13C and d15N), soil organic C (SOC) chemical composition, and N mineralization among plant communities. After 12 to 15 years of open top chamber (OTC) treatment no statistical effect was found on the soil temperature (10 cm soil depth), although the was an overall increase in all OTC by +0.2°C. However, the soil moisture decreased significantly by 3-14%, depending on plant community, in the OTCs compared to ambient conditions. Preliminary, there was a 19-61% non-significant increase in annual growing season ER in the OTC compared to the ambient plots over the growing season. The were distinct differences in the SOM functional composition among plant communities with c 10% more O-alkyls stored in tussock tundra than in dry meadow. The OTCs did not consistently alter the SOM composition among the vegetation types but clearly showed a trend for reduced aliphatic and O-alkyl C in the OTCs suggesting increased decomposition (or reduced inputs) of these compounds. Thus, the non-significantly higher ER may in some communities be of plant origin linked to greater plant biomass in the OTCs, and in other (e.g. tussock tundra) from increased decomposition rates. In conclusion, this study showed that 12-15 years of OTC treatment had a modest effects impact C and N dynamics in tundra soils specific to distinct plant communities.
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| 6. |
- Ladd, Brenton, et al.
(författare)
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Carbon isotopic signatures of soil organic matter correlate with leaf area index across woody biomes
- 2014
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 102:6, s. 1606-1611
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Tidskriftsartikel (refereegranskat)abstract
- Leaf area index (LAI), a measure of canopy density, is a key variable for modelling and understanding primary productivity, and also water use and energy exchange in forest ecosystems. However, LAI varies considerably with phenology and disturbance patterns, so alternative approaches to quantifying stand-level processes should be considered. The carbon isotope composition of soil organic matter (C-13(SOM)) provides a time-integrated, productivity-weighted measure of physiological and stand-level processes, reflecting biomass deposition from seasonal to decadal time scales.Our primary aim was to explore how well LAI correlates with C-13(SOM) across biomes.Using a global data set spanning large environmental gradients in tropical, temperate and boreal forest and woodland, we assess the strength of the correlation between LAI and C-13(SOM); we also assess climatic variables derived from the WorldClim database.We found that LAI was strongly correlated with C-13(SOM), but was also correlated with Mean Temperature of the Wettest Quarter, Mean Precipitation of Warmest Quarter and Annual Solar Radiation across and within biomes.Synthesis. Our results demonstrate that C-13(SOM) values can provide spatially explicit estimates of leaf area index (LAI) and could therefore serve as a surrogate for productivity and water use. While C-13(SOM) has traditionally been used to reconstruct the relative abundance of C-3 versus C-4 species, the results of this study demonstrate that within stable C-3- or C-4-dominated biomes, C-13(SOM) can provide additional insights. The fact that LAI is strongly correlated to C-13(SOM) may allow for a more nuanced interpretation of ecosystem properties of palaeoecosystems based on palaeosol C-13 values.
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| 7. |
- Lindgren, Anders E. G., et al.
(författare)
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Chemical Probes to Study ADP-Ribosylation : Synthesis and Biochemical Evaluation of Inhibitors of the Human ADP-Ribosyltransferase ARTD3/PARP3
- 2013
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:23, s. 9556-9568
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Tidskriftsartikel (refereegranskat)abstract
- The racemic 3-(4-oxo-3,4-dihydroquinazolin-2-yl)-N-[1-(pyridin-2-yl)ethyl]propanamide, 1, has previously been identified as a potent but unselective inhibitor of diphtheria toxin-like ADP-ribosyltransferase 3 (ARTD3). Herein we describe synthesis and evaluation of SS compounds in this class. It was found that the stereochemistry is of great importance for both selectivity and potency and that substituents on the phenyl ring resulted in poor solubility. Certain variations at the meso position were tolerated and caused a large shift in the binding pose. Changes to the ethylene linker that connects the quinazolinone to the amide were also investigated but proved detrimental to binding. By combination of synthetic organic chemistry and structure-based design, two selective inhibitors of ARTD3 were discovered.
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| 8. |
- Lindgren, Anders E. G., et al.
(författare)
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PARP Inhibitor with Selectivity Toward ADP-Ribosyltransferase ARTD3/PARP3
- 2013
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 8:8, s. 1698-1703
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Tidskriftsartikel (refereegranskat)abstract
- Inhibiting ADP-ribosyl transferases with PARP-inhibitors is considered a promising strategy for the treatment of many cancers and ischemia, but most of the cellular targets are poorly characterized. Here, we describe an inhibitor of ADP-ribosyltransferase-3/poly(ADP-ribose) polymerase-3 (ARTD3), a regulator of DNA repair and mitotic progression. In vitro profiling against 12, members of the enzyme family suggests selectivity for ARTD3, and crystal structures illustrate the molecular basis for inhibitor selectivity. The compound is active in cells, where it elicits ARTD3-specific effects at submicromolar concentration. Our results show that by targeting the nicotinamide binding site, selective inhibition can be achieved among the closest relatives of the validated clinical target, ADP-ribosyltransferase-1/poly(ADP-ribose) polymerase-1.
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| 9. |
- Orlova, Anna, et al.
(författare)
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Site-specific radiometal labeling and improved biodistribution using ABY-027, a novel HER2-targeting affibody molecule-albumin-binding domain fusion protein
- 2013
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 54:6, s. 961-968
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Tidskriftsartikel (refereegranskat)abstract
- Because of their better penetration, smaller targeting proteins may be superior to antibodies for radioimmunotherapy of solid tumors. Therefore, Affibody molecules (6.5 kDa) have a potential for being suitable as targeted moiety for radiolabeled therapeutic proteins. Previous studies have demonstrated that a fusion of an Affibody molecule with an albumin-binding domain (ABD) provides a strong noncovalent binding to albumin in vivo. This strong noncovalent binding can be used for reduction of the renal uptake of the Affibody molecule while maintaining a size smaller than that of an antibody, which is important when using residualizing radionuclide labels conjugated to Affibody molecules. The goal of this study was to design and evaluate a new targeting Affibody - ABD fusion protein with improved biodistribution properties for radionuclide therapy. Methods: A novel Affibody-based construct, Z HER2:2891-ABD035-DOTA (ABY-027), was created by fusion of the reengineered HER2-binding Affibody molecule ZHER2:2891 to the N terminus of the high-affinity ABD035, and a maleimido-derivative of DOTA was conjugated at the C terminus of the construct. Binding and processing of 177Lu-ABY-027 by HER2-expressing cells were evaluated in vitro. Targeting of HER2-expressing SKOV-3 xenografts was evaluated in BALB/C nu/nu mice and compared with targeting of previously reported ABD-(Z HER2:342)2. Results: The binding affinity (dissociation constant) of ABY-027 to HER2 (74 pM) was the same as for the parental Z HER2:2891 (76 pM). ABY-027 was stably labeled with 177Lu and 111In with preserved specific binding to HER2-expressing cells in vitro. In vivo receptor saturation experiments demonstrated that targeting of SKOV-3 xenografts in BALB/C nu/nu mice was HER2-specific. 177Lu-ABY- 027 demonstrated substantially (2- to 3-fold) lower renal and hepatic uptake than previously assessed HER2-specific Affibody-based albumin-binding agents. Tumor uptake of radiolabeled ABY-027 at 48 h after injection was 2-fold higher than that for previously reported ABD-(ZHER2:342)2. Conclusion: An optimized molecular design of an ABD fusion protein resulted in an Affibody molecule construct with better properties for therapy. Fully preserved in vivo targeting of the fusion protein was shown in xenografted mice. Site-specific coupling of DOTA provides a uniform conjugate and creates the potential for labeling with a broad range of therapeutic radionuclides. The biodistribution of 177Lu-ABY-027 in a murine model suggests it is more suitable for therapy than alternative approaches.
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| 10. |
- Thomsson, Elisabeth, 1975, et al.
(författare)
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Recombinant glycoprotein E produced in mammalian cells in large-scale as an antigen for varicella-zoster-virus serology.
- 2011
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Ingår i: Journal of virological methods. - : Elsevier BV. - 1879-0984 .- 0166-0934. ; 175:1, s. 53-9
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Tidskriftsartikel (refereegranskat)abstract
- A recombinant glycoprotein E (gE) from varicella-zoster virus (VZV) was generated and produced in Chinese Hamster Ovary (CHO) cells, in the development of a specific antigen for analysis of IgG antibodies to VZV. Several stable gE-secreting clones were established and one clone was adapted to growth in serum-free suspension culture. When the cells were cultured in a perfusion bioreactor, gE was secreted into the medium, from where it could be easily purified. The recombinant gE was then evaluated as a serological antigen in ELISA. When compared to a conventional whole virus antigen, the VZV gE showed similar results in ELISA-based seroprevalence studies of 854 samples derived from blood donors, students, ischemic stroke patients and their controls, including samples with border-line results in previous analyses. Eight samples (0.9%) were discordant, all being IgG-negative by the VZV gE ELISA and positive by the whole virus ELISA. The sensitivity and specificity of the VZV gE ELISA were 99.9% and 100%, respectively, compared to 100% and 88.9% for the VZV whole virus ELISA. The elderly subjects showed similar reactivities to both antigens, while VZV gE gave lower signals in the younger cohorts, suggesting that antibodies to gE may increase with age. It was concluded that the recombinant VZV gE from CHO cells was suitable as a serological antigen for the detection of IgG antibodies specific for VZV.
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| 11. |
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| 12. |
- Wallander, Håkan, et al.
(författare)
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Evaluation of methods to estimate production, biomass and turnover of ectomycorrhizal mycelium in forests soils : a review
- 2013
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Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 57, s. 1034-1047
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Forskningsöversikt (refereegranskat)abstract
- Mycorrhizal fungi constitute a considerable sink for carbon in most ecosystems. This carbon is used for building extensive mycelial networks in the soil as well as for metabolic activity related to nutrient uptake. A number of methods have been developed recently to quantify production, standing biomass and turnover of extramatrical mycorrhizal mycelia (EMM) in the field. These methods include minirhizotrons, in-growth mesh bags and cores, and indirect measurements of EMM based on classification of ectomycorrhizal fungi into exploration types. Here we review the state of the art of this methodology and discuss how it can be developed and applied most effectively in the field, Furthermore, we also discuss different ways to quantify fungal biomass based on biomarkers such as chitin, ergosterol and PLFAs, as well as molecular methods, such as qPCR. The evidence thus far indicates that mycorrhizal fungi are key components of microbial biomass in many ecosystems. We highlight the need to extend the application of current methods to focus on a greater range of habitats and mycorrhizal types enabling incorporation of mycorrhizal fungal biomass and turnover into biogeochemical cycling models.
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| 13. |
- Wennerberg, Erik, et al.
(författare)
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Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells
- 2014
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 20:22, s. 5733-5744
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive forms of cancer with no curative therapies available. To date, strategies to target ATC by immunotherapy have not been evaluated. We investigated whether ATC would be a suitable target for natural killer (NK) cell-based immunotherapy.EXPERIMENTAL DESIGN: We first established seven new cell lines from ATC tumors, three from papillary thyroid carcinoma tumors and analyzed them together with eight additional ATC cell lines. Cells were analyzed for sensitivity to lysis by NK cells and their ability to chemoattract and regulate the activity of NK cells. In addition, fresh tumor samples and peripheral blood from six patients with ATC were analyzed for NK cell infiltration and phenotype.RESULTS: We observed that ATC cell lines are sensitive to lysis by ex vivo expanded NK cells and that the lysis was abrogated upon blockade of NKG2D. Sensitivity of thyroid cancer cell lines to NK cell-mediated lysis correlated with surface expression of UL16-binding protein 2 on tumor cells. Moreover, ATC cell lines produced high levels of CXCL10 and stimulated migration of expanded NK cells and ATC tumors were enriched for NK cells expressing the cognate chemokine receptor CXCR3. However, compared with NK cells in peripheral blood, ATC tumor-derived NK cells displayed a suppressed phenotype with a downregulated expression of NKG2D. In vitro, suppression of NK cell-mediated lysis and NKG2D expression by ATC cells was restored upon neutralization of prostaglandin-E2.CONCLUSIONS: ATC cell lines are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract CXCR3-positive NK cells. Patients with ATC may benefit from NK cell-based immunotherapy.
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| 14. |
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| 15. |
- Zhao, J., et al.
(författare)
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Transdifferentiation of autologous bone marrow cells on a collagen-poly(epsilon-caprolactone) scaffold for tissue engineering in complete lack of native urothelium
- 2014
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 11:96
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Tidskriftsartikel (refereegranskat)abstract
- Urological reconstructive surgery is sometimes hampered by a lack of tissue. In some cases, autologous urothelial cells (UCs) are not available for cell expansion and ordinary tissue engineering. In these cases, we wanted to explore whether autologous mesenchymal stem cells (MSCs) from bone marrow could be used to create urological transplants. MSCs from human bone marrow were cultured in vitro with medium conditioned by normal human UCs or by indirect co-culturing in culture well inserts. Changes in gene expression, protein expression and cell morphology were studied after two weeks using western blot, RT-PCR and immune staining. Cells cultured in standard epithelial growth medium served as controls. Bone marrow MSCs changed their phenotype with respect to growth characteristics and cell morphology, as well as gene and protein expression, to a UC lineage in both culture methods, but not in controls. Urothelial differentiation was also accomplished in human bone marrow MSCs seeded on a three-dimensional poly(epsilon-caprolactone) (PCL)-collagen construct. Human MSCs could easily be harvested by bone marrow aspiration and expanded and differentiated into urothelium. Differentiation could take place on a three-dimensional hybrid PCL-reinforced collagen-based scaffold for creation of a tissue-engineered autologous transplant for urological reconstructive surgery.
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