| 1. |
- Barkefors, Irmeli, et al.
(författare)
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Exocyst Complex Component 3-like 2 (EXOC3L2) Associates with the Exocyst Complex and Mediates Directional Migration of Endothelial Cells
- 2011
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:27, s. 24189-24199
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Tidskriftsartikel (refereegranskat)abstract
- The exocyst is a protein complex that ensures spatial targeting of exocytotic vesicles to the plasma membrane. We present microarray data obtained from differentiating mouse embryonic stem cell cultures that identify an up-regulation of exocyst complex component 3-like 2 (exoc3l2) mRNA in sprouting blood vessels. Vascular expression of exoc3l2 is confirmed by qPCR analysis of different mouse tissues and immunofluorescence analyses of mouse brain sections. We detect an up-regulation of exoc3l2 mRNA synthesis in primary human endothelial cells in response to VEGFA, and this response is enhanced when the cells are grown on a three-dimensional collagen I matrix. Myc-tagged EXOC3L2 co-precipitates with the exocyst protein EXOC4, and immunofluorescence detection of EXOC3L2 shows partial subcellular colocalization with EXOC4 and EXOC7. Finally, we show that exoc3l2 silencing inhibits VEGF receptor 2 phosphorylation and VEGFA-directed migration of cultured endothelial cells.
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| 2. |
- Baskaran, Sathishkumar, et al.
(författare)
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Primary glioblastoma cells for precision medicine : a quantitative portrait of genomic (in)stability during the first 30 passages
- 2018
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Ingår i: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 20:8, s. 1080-1091
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary glioblastoma cell (GC) cultures have emerged as a key model in brain tumor research, with the potential to uncover patient-specific differences in therapy response. However, there is limited quantitative information about the stability of such cells during the initial 20-30 passages of culture.Methods: We interrogated 3 patient-derived GC cultures at dense time intervals during the first 30 passages of culture. Combining state-of-the-art signal processing methods with a mathematical model of growth, we estimated clonal composition, rates of change, affected pathways, and correlations between altered gene dosage and transcription.Results: We demonstrate that GC cultures undergo sequential clonal takeovers, observed through variable proportions of specific subchromosomal lesions, variations in aneuploid cell content, and variations in subpopulation cell cycling times. The GC cultures also show significant transcriptional drift in several metabolic and signaling pathways, including ribosomal synthesis, telomere packaging and signaling via the mammalian target of rapamycin, Wnt, and interferon pathways, to a high degree explained by changes in gene dosage. In addition to these adaptations, the cultured GCs showed signs of shifting transcriptional subtype. Compared with chromosomal aberrations and gene expression, DNA methylations remained comparatively stable during passaging, and may be favorable as a biomarker.Conclusion: Taken together, GC cultures undergo significant genomic and transcriptional changes that need to be considered in functional experiments and biomarker studies that involve primary glioblastoma cells.
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| 3. |
- Berg, Tracy J., et al.
(författare)
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The Irradiated Brain Microenvironment Supports Glioma Stemness and Survival via Astrocyte-Derived Transglutaminase 2
- 2021
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Ingår i: Cancer Research. - : American Association For Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 81:8, s. 2101-2115
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Tidskriftsartikel (refereegranskat)abstract
- The tumor microenvironment plays an essential role in supporting glioma stemness and radioresistance. Following radiotherapy, recurrent gliomas form in an irradiated microenvironment. Here we report that astrocytes, when pre-irradiated, increase stemness and survival of cocultured glioma cells. Tumor-naive brains increased reactive astrocytes in response to radiation, and mice subjected to radiation prior to implantation of glioma cells developed more aggressive tumors. Extracellular matrix derived from irradiated astrocytes were found to be a major driver of this phenotype and astrocyte-derived transglutaminase 2 (TGM2) was identified as a promoter of glioma stemness and radioresistance. TGM2 levels increased after radiation in vivo and in recurrent human glioma, and TGM2 inhibitors abrogated glioma stemness and survival. These data suggest that irradiation of the brain results in the formation of a tumor-supportive microenvironment. Therapeutic targeting of radiation-induced, astrocyte-derived extracellular matrix proteins may enhance the efficacy of standard-of-care radiotherapy by reducing stemness in glioma. Significance: These findings presented here indicate that radiotherapy can result in a tumor-supportive microenvironment, the targeting of which may be necessary to overcome tumor cell therapeutic resistance and recurrence.
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| 4. |
- Bergström, Ann-Kristin, et al.
(författare)
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Contrasting plankton stoichiometry and nutrient regeneration in northern arctic and boreal lakes
- 2018
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Ingår i: Aquatic Sciences. - : Springer. - 1015-1621 .- 1420-9055. ; 80:2
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Tidskriftsartikel (refereegranskat)abstract
- Contrasting carbon: nitrogen: phosphorus (C: N: P) stoichiometry between phytoplankton and zooplankton affect consumer growth and phytoplankton nutrient limitation via nutrient recycling by zooplankton. However, no study has assessed how regional differences in terrestrial loadings of organic matter affect plankton N: P stoichiometry and recycling in systems with low N deposition and N-limited phytoplankton. We address this question by using data from 14 unproductive headwater arctic and boreal lakes. We found that boreal lakes had higher lake water-and seston C, N and P concentrations than arctic lakes, whereas seston C: N, C: P and N: P ratios did not differ among regions. Boreal zooplankton were also richer in N and P relative to C, with lower somatic N: P ratios, compared to arctic lakes. Consequently, the estimated N: P imbalances between seston and zooplankton were negative in arctic lakes, indicating zooplankton feeding on phytoplankton of suboptimal N content, resulting in low consumer driven N: P recycling (medians arctic sub-mid and high altitude lakes: 11 and 13). In boreal lakes, estimated N: P imbalance did not differ from zero, with a seston N: P stoichiometry matching the N: P requirements of zooplankton, which resulted in higher consumer driven N: P recycling (median 18). Our results imply that regional climate induced catchment differences, through enhanced terrestrial nutrient inputs, affect plankton stoichiometry by raising consumer N: P recycling ratio and changing zooplankton from being mainly N-(arctic) to NP co-limited (boreal). Browning of lakes, in regions with low N deposition, may therefore promote large-scale regional changes in plankton nutrient limitation with potential feedbacks on pelagic food webs.
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| 5. |
- Bergström, Ann-Kristin, 1968-, et al.
(författare)
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Declining calcium concentration drives shifts toward smaller and less nutritious zooplankton in northern lakes
- 2024
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 30:3
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Tidskriftsartikel (refereegranskat)abstract
- Zooplankton community composition of northern lakes is changing due to the interactive effects of climate change and recovery from acidification, yet limited data are available to assess these changes combined. Here, we built a database using archives of temperature, water chemistry and zooplankton data from 60 Scandinavian lakes that represent broad spatial and temporal gradients in key parameters: temperature, calcium (Ca), total phosphorus (TP), total organic carbon (TOC), and pH. Using machine learning techniques, we found that Ca was the most important determinant of the relative abundance of all zooplankton groups studied, while pH was second, and TOC third in importance. Further, we found that Ca is declining in almost all lakes, and we detected a critical Ca threshold in lake water of 1.3 mg L−1, below which the relative abundance of zooplankton shifts toward dominance of Holopedium gibberum and small cladocerans at the expense of Daphnia and copepods. Our findings suggest that low Ca concentrations may shape zooplankton communities, and that current trajectories of Ca decline could promote widespread changes in pelagic food webs as zooplankton are important trophic links from phytoplankton to fish and different zooplankton species play different roles in this context.
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| 6. |
- Bergström, Ann-Kristin, 1968-, et al.
(författare)
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Effects of nitrogen enrichment on zooplankton biomass and N:P recycling ratios across a DOC gradient in northern-latitude lakes
- 2021
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Ingår i: Hydrobiologia. - : Springer. - 0018-8158 .- 1573-5117. ; 848:21, s. 4991-5010
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Tidskriftsartikel (refereegranskat)abstract
- We used data from whole-lake studies to assess how changes in food quantity (phytoplankton biomass) and quality (phytoplankton community composition, seston C:P and N:P) with N fertilization affect zooplankton biomass, community composition and C:N:P stoichiometry, and their N:P recycling ratio along a gradient in lake DOC concentrations. We found that despite major differences in phytoplankton biomass with DOC (unimodal distributions, especially with N fertilization), no major differences in zooplankton biomass were detectable. Instead, phytoplankton to zooplankton biomass ratios were high, especially at intermediate DOC and after N fertilization, implying low trophic transfer efficiencies. An explanation for the observed low phytoplankton resource use, and biomass responses in zooplankton, was dominance of colony forming chlorophytes of reduced edibility at intermediate lake DOC, combined with reduced phytoplankton mineral quality (enhanced seston N:P) with N fertilization. N fertilization, however, increased zooplankton N:P recycling ratios, with largest impact at low DOC where phytoplankton benefitted from light sufficiently to cause enhanced seston N:P. Our results suggest that although N enrichment and increased phytoplankton biomass do not necessarily increase zooplankton biomass, bottom-up effects may still impact zooplankton and their N:P recycling ratio through promotion of phytoplankton species of low edibility and altered mineral quality.
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| 7. |
- Bergström, Ann-Kristin, et al.
(författare)
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N-limited consumer growth and low nutrient regeneration N:P ratios in lakes with low N deposition
- 2015
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Ingår i: Ecosphere. - 2150-8925 .- 2150-8925. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Nutrient limitation of primary producers and their consumers can have a large influence on ecosystem productivity. The nature and strength of nutrient limitation is driven both by external factors (e.g., nutrient loading) and internal processes (e.g., consumer-driven nutrient regeneration). Here we present results from a field study in 10 low productive headwater lakes in northern subarctic Sweden, where nitrogen (N) deposition is low and phytoplankton is primarily N-limited. We assessed the carbon:nitrogen:phosphorus (C:N:P) stoichiometry of seston and zooplankton and estimated the N:P ratio of consumer-driven nutrient regeneration. Based on stoichiometric models, the estimated elemental imbalances between seston and zooplankton suggest that zooplankton were mainly N-limited and regenerated nutrients with low N:P ratios (median 11.9, atomic ratio). The predicted N:P regeneration ratios were consistent with results from phytoplankton nutrient limitation bioassays in mid-summer, i.e., the N:P regeneration was predicted to be low when phytoplankton were N-limited, and high when phytoplankton were P-limited. During other seasons, when water discharge was high, nutrient loading from the surrounding catchments apparently had the strongest effect on phytoplankton nutrient limitation. We propose that lakes with higher N:P ratios than the open ocean is an effect of N deposition, that N-limitation of consumers and phytoplankton is further enhanced by low nutrient regeneration N:P ratios, and that in the absence of N deposition, lake and ocean N:P stoichiometry are similar.
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| 8. |
- Bergström, Kristofer, et al.
(författare)
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Exceptional longevity in northern peripheral populations of Wels catfish (Siluris glanis)
- 2022
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Studies of life-history variation across a species range are crucial for ecological understanding and successful conservation. Here, we examined the growth and age of Wels catfish (Silurus glanis) in Sweden, which represent the northernmost populations in Europe. A total of 1183 individuals were captured, marked and released between 2006 and 2020. Mark-recapture data from 162 individuals (size range: 13-195 cm) were used to estimate von Bertalanffy growth curve parameters which revealed very slow growth rates compared to catfish within the core distribution area (central Europe). The fitted von Bertalanffy growth curve predicted a 150 cm catfish to be around 40 years old, while the largest recaptured individual (length 195 cm) was estimated to be 70 (95% CI 50-112) years old. This was substantially older than the previously documented maximum age of a catfish. The weight at length relationships in these northern peripheral populations were similar to those documented for catfish in central Europe indicating that resources did not constrain growth. This indicates that the slow growth and exceptional high age in the northern catfish populations are the result of lower temperatures and/or local adaptations.
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| 9. |
- Bergström, Lars Magnus, et al.
(författare)
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Synergistic effects in mixtures of oppositely charged surfactants as calculated from the Poisson-Boltzmann theory : A comparison between theoretical predictions and experiments
- 2008
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 322:2, s. 589-595
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Tidskriftsartikel (refereegranskat)abstract
- Critical micelle concentrations in mixtures of an anionic surfactant and a cationic amphiphilic drug have been investigated using a model-independent procedure to quantify observed synergistic effects. Experimental results were compared with a theory based on the Poisson-Boltzmann mean field approximation of a charged interface with a diffuse layer of counterions. Explicit expressions for the activity coefficients from which the critical micelle concentration can be calculated and quantitatively predicted have been derived and excellent agreement between experimental data and theory was obtained. As a result, we demonstrate that it is possible to rationalize and predict the magnitude of synergism in mixtures of oppositely charged surfactants in the presence of added salt.
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| 10. |
- Bergström, Mattias, et al.
(författare)
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Needs as a basis for design rationale
- 2008
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Konferensbidrag (refereegranskat)abstract
- A basic principle for Needfinding [Faste, 1987; Patnaik & Becker, 1999] is that designers and engineers should interact directly with users to get direct insights into the user domain. Needfinding is not a new phenomena, it is almost forty years ago since the process was adopted at Stanford University’s product design program [Patnaik & Becker, 1999]. As the name, Need-finding, implies, this is an intertwined approach to find needs which are not readily articulated by users. The application of a Needfinding process offers qualitative methods to make those needs visible early on in product development. In fact, the process has become more interesting during recent time, since qualitative methods have gained more acceptance outside the academic realm [ibid.].The word qualitative indicates that what are sought for are qualities such as people’s experiences, what they perceive or interpret into a situation [Miles & Huberman, 1994; Patton, 2002]. Such data is contextually dependent, i.e., it must be generated in the context in which the phenomena occur. Besides context, people’s activities, behaviours and goals are important to observe and learn from. The objectives, for applying Needfinding, are to make the identification of needs and design a seamless effort, as well as an interest to identify opportunities to innovations. Needs last longer than any solution [Patnaik & Becker, 1999], since they are grounded in people’s activities. The solution and product that might meet such needs change over time. One example is how to store computer data, the products which satisfy the need has changed from, e.g., punch cards, magnetic tape, floppy discs [ibid.] to USB-flash memories. A guiding methodology in Needfinding is a flexible process, which is adapted to the task at hand [Kelley, 2001]. Such a process is conveyed in a few basic steps and, builds on a ‘philosophy’ which permeates all activities in order to adapt the process according to the project. Therefore, the designer’s ability to rely on such a process depends on familiarity with a number of methods for observations and interviews, as well as an aptitude for socio-technical skills. Hence, the purpose in this paper is to present and reflect on methods used in a running development project to identify needs in a product development project. This is done to contribute to the advancement of a need driven product development process. The disposition of this paper is as follows. First, our approach in studying the need identification activities is presented. Second, a theoretical frame for need identification and design is presented, i.e., Needfinding [Patnaik & Becker, 1999]. Third, the practice of finding needs is outlined and discussed.
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