| 1. |
- Dimberg, Anna, et al.
(author)
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alphaB-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis
- 2008
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:4, s. 2015-2023
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Journal article (peer-reviewed)abstract
- Selective targeting of endothelial cells in tumor vessels requires delineation of key molecular events in formation and survival of blood vessels within the tumor microenvironment. To this end, proteins transiently up-regulated during vessel morphogenesis were screened for their potential as targets in antiangiogenic tumor therapy. The molecular chaperone alpha B-crystallin was identified as specifically induced with regard to expression level, modification by serine phosphorylation, and subcellular localization during tubular morphogenesis of endothelial cells. Small interfering RNA-mediated knockdown of alpha B-crystallin expression did not affect endothelial proliferation but led to attenuated tubular morphogenesis, early activation of proapoptotic caspase-3, and increased apoptosis. alpha B-crystallin was expressed in a subset of human tumor vessels but not in normal capillaries. Tumors grown in alpha B-crystallin(-/-) mice were significantly less vascularized than wild-type tumors and displayed increased areas of apoptosis/necrosis. Importantly, tumor vessels in alpha B-crystallin(-/-) mice were leaky and showed signs of caspase-3 activation and extensive apoptosis. Ultrastructural analyses showed defective vessels partially devoid of endothelial lining. These data strongly implicate alpha B-crystallin as an important regulator of tubular morphogenesis and survival of endothelial cell during tumor angiogenesis. Hereby we identify the small heat shock protein family as a novel class of anglogenic modulators.
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| 2. |
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| 3. |
- Lindholm, Anna, et al.
(author)
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Hierarchical scheduling and utility disturbance management in the process industry
- 2013
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In: 7th IFAC Conference on Manufacturing Modelling, Management, and Control, 2013. - : Elsevier. - 1474-6670. - 9783902823359 ; , s. 140-145
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Conference paper (peer-reviewed)abstract
- The integration of scheduling and control in the process industry is a topic that has been frequently discussed during the recent years, but many challenges remain in order to achieve integrated solutions that can be implemented for large-scale industrial sites. In this paper we consider production control under disturbances in the supply of utilities at integrated sites together with the integration towards production scheduling. Utilities, such as steam and cooling water, are often shared between the production areas of a site, which enables formulation of an optimization problem for determining the optimal supply of utilities to each area at the occurrence of a disturbance. Optimization in two timescales is suggested to handle the scheduling and disturbance management problems in a hierarchical fashion. The suggested structure has been discussed with companies within the chemical process industry. A simple example is provided to show how the structure may be used.
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| 4. |
- Matsumoto, Taro, et al.
(author)
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Ninein Is Expressed in the Cytoplasm of Angiogenic Tip-Cells and Regulates Tubular Morphogenesis of Endothelial Cells
- 2008
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 28, s. 2123-2130
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Journal article (peer-reviewed)abstract
- Objective— Angiogenesis is an integral part of many physiologicalprocesses but may also aggravate pathological conditions suchas cancer. Development of effective angiogenesis inhibitorsrequires a thorough understanding of the molecular mechanismsregulating vessel formation. The aim of this project was toidentify proteins that regulate tubular morphogenesis of endothelialcells.Methods and Results— Phosphotyrosine-dependent affinity-purificationand mass spectrometry showed tyrosine phosphorylation of nineinduring tubular morphogenesis of endothelial cells. Ninein wasrecently identified as a centrosomal microtubule-anchoring protein.Our results show that ninein is localized in the cytoplasm inendothelial cells, and that it is highly expressed in the vasculaturein normal and pathological human tissues. Using embryoid bodiesas a model of vascular development, we found that ninein isabundantly expressed in the cytoplasm of endothelial cells duringsprouting angiogenesis, in particular in the sprouting tip-cell.In accordance, siRNA-dependent silencing of ninein in endothelialcells inhibited tubular morphogenesis.Conclusions— In this study, we show that ninein is expressedin developing vessels and in endothelial tip cells, and thatninein is critical for formation of the vascular tube. Thesedata strongly implicate ninein as an important new regulatorof angiogenesis.Proteins orchestrating morphological changes accompanying formationof the vascular tube constitute new targets for antiangiogenictherapy. In this study, we identify the microtubule-anchoringprotein ninein as an important new regulator of tubular morphogenesisof endothelial cells. This is the first report of a functionalrole of ninein in angiogenesis.
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| 5. |
- Matsumoto, Taro, et al.
(author)
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VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis.
- 2005
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In: EMBO J. - 0261-4189. ; 24:13, s. 2342-53
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Journal article (peer-reviewed)abstract
- Vascular endothelial growth factor receptor-2 (VEGFR-2) activation by VEGF-A is essential in vasculogenesis and angiogenesis. We have generated a pan-phosphorylation site map of VEGFR-2 and identified one major tyrosine phosphorylation site in the kinase insert (Y951), in addition to two major sites in the C-terminal tail (Y1175 and Y1214). In developing vessels, phosphorylation of Y1175 and Y1214 was detected in all VEGFR-2-expressing endothelial cells, whereas phosphorylation of Y951 was identified in a subset of vessels. Phosphorylated Y951 bound the T-cell-specific adapter (TSAd), which was expressed in tumor vessels. Mutation of Y951 to F and introduction of phosphorylated Y951 peptide or TSAd siRNA into endothelial cells blocked VEGF-A-induced actin stress fibers and migration, but not mitogenesis. Tumor vascularization and growth was reduced in TSAd-deficient mice, indicating a critical role of Y951-TSAd signaling in pathological angiogenesis.
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| 6. |
- Nydahl, Anna, 1981-
(author)
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Coastal microbial respiration in a climate change perspective
- 2012
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Doctoral thesis (other academic/artistic)abstract
- In a climate change perspective increased precipitation and temperature are expected which should influence the coastal microbial food web. Precipitation will have a strong impact on river flow and thereby increase the carbon input to the coastal zone as well as lowering the marine salinity by dilution with freshwater. Simultaneously temperature may increase by 2-5 °C, potentially influencing e.g. metabolic processes. Consequences of this have been evaluated in this thesis with focus on microbial respiration in paper II and IV. A temperature increase of 3 °C will have a marked effect on microbial respiration rates in the coastal zone. The effect of temperature on microbial respiration showed a median Q10 value of 25 with markedly higher values during winter conditions (around 0°C). These Q10 values are several-fold higher than found in oceanic environments. The conclusion was in accordance with a consistent temperature limitation of microbial respiration during an annual field study, however, shifting to DOC limitation at the elevated temperature. Neither bacterial production nor phytoplankton production showed a consistent temperature effect, suggesting that the biomass production at the base of the food web is less sensitive to a temperature increase. Results from both a field study and a fully factorial microcosm experiment supported the conclusion. Our results suggested that areas dealing with hypoxia today will most likely expand in the future, due to increased respiration caused by higher temperatures and larger riverine output of dissolved organic carbon. Pelagic respiration measurements in the sea are relatively scarce in the literature, mainly due to the lack of sufficiently good and user friendly techniques. New methods such as the dynamic luminescence quenching technique for oxygen concentration have been developed. This makes it possible to obtain continuous measurements of oxygen in an enclosed vial. Two different commercially available systems based on the dynamic luminescence quenching technique were evaluated from the aspect of precision, accuracy and detection limit when applied to respiration measurements in natural pelagic samples. The Optode setup in paper III showed a practical detection limit of 0.30 mmol m-3 d-1, which can be applied to measure respiration in productive coastal waters (used in paper IV). This included development of a stopper where the sensor was attached, stringent temperature control, proper stirring and compensation for an observed system drift. For controlled laboratory experiments with organisms smaller than 1 µm the Sensor Dish Reader (paper I) has sufficient detection limit of (4.8 mmol m-3 d-1). This required a stringent temperature control and manual temperature correction. The Sensor Dish Reader gives the opportunity to perform multiple treatments at low cost (used in paper II), but the precision is too low for field studies due to the between ampule variation.
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| 7. |
- Nydahl, Anna, 1981-, et al.
(author)
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Increased microbial activity in a warmer and wetter climate enhances the risk of coastal hypoxia
- 2013
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In: FEMS Microbiology Ecology. - Hoboken : Wiley-Blackwell. - 0168-6496 .- 1574-6941. ; 85:2, s. 338-347
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Journal article (peer-reviewed)abstract
- The coastal zone is the most productive area of the marine environment and the area that is most exposed to environmental drivers associated with human pressures in a watershed. In dark bottle incubation experiments, we investigated the short-term interactive effects of changes in salinity, temperature and riverine dissolved organic matter (rDOM) on microbial respiration, growth and abundance in an estuarine community. An interaction effect was found for bacterial growth, where the assimilation of rDOM increased at higher salinities. A 3 °C rise in the temperature had a positive effect on microbial respiration. A higher concentration of DOM consistently enhanced respiration and bacterial abundance, while an increase in temperature reduced bacterial abundance. The latter result was most likely caused by a positive interaction effect of temperature, salinity and rDOM on the abundance of bacterivorous flagellates. Elevated temperature and precipitation, causing increased discharges of rDOM and an associated lowered salinity, will therefore primarily promote bacterial respiration, growth and bacterivore abundance. Our results suggest a positive net outcome for microbial activity under the projected climate change, driven by different, partially interacting environmental factors. Thus, hypoxia in coastal zones may increase due to enhanced respiration caused by higher temperatures and rDOM discharge acting synergistically.
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| 8. |
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| 9. |
- Panigrahi, Satya, et al.
(author)
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Strong seasonal effect of moderate experimental warming on plankton respiration in a temperate estuarine plankton community
- 2013
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In: Estuarine, Coastal and Shelf Science. - : Academia Press. - 0272-7714 .- 1096-0015. ; 136, s. 269-279
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Journal article (peer-reviewed)abstract
- Climate change projections forecast a 1.1-6.4 °C global increase in surface water temperature and a 3 °C increase for the Baltic Sea. This study examined the short-term interactive effects of a realistic future temperature increase (3 °C) on pelagic respiration and bacterioplankton growth and phytoplanktonphotosynthesis in situ. This study was undertaken throughout a full seasonal cycle in the northern Baltic Sea. We found marked positive short-term effects of temperature on plankton respiration but no significant effect on bacterioplankton growth or phytoplankton photosynthesis. Absolute respiration rates remained similar to other comparable environments at the in situ temperature. With the 3 °C temperature increase, respiration rates in situ increased up to 5-fold during the winter and 2-fold during the summer. A maximum seasonal Q10 value of 332 was observed for respiration during the cold winter months (twater z 0 C), and summer Q10 values were comparatively high (9.1). Q10 values exhibited a significant inverse relationship to water temperature during winter. Our results thereby suggest that plankton respiration in this coastal zone is more temperature sensitive than previously reported. In addition, field data indicated that plankton respiration switched from being temperature limited to being limited by dissolved organic carbon (DOC) after the simulated temperature increase. Assuming that our observations are relevant over longer time scales, climate change may worsen hypoxia, increase CO2 emissions and create a more heterotrophic food web in coastal zones with a high load of riverine DOC.
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| 10. |
- Sandström, Anette, et al.
(author)
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Exercise capacity in adult patients with tetralogy of Fallot
- 2021
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In: International Journal of Cardiology Congenital Heart Disease. - : Elsevier. - 2666-6685. ; 5
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Journal article (peer-reviewed)abstract
- Background: On a group level, patients with repaired tetralogy of Fallot have impaired exercise capacity. Since exercise capacity is related to prognosis, and more patients survive into higher age, it is important to know the expected exercise capacity at different ages. Furthermore, factors associated with exercise capacity and the relation between exercise capacity and mortality need further evaluation.Methods: The national register of congenital heart disease was searched for exercise tests in adults with repaired tetralogy of Fallot. The results from exercise tests were compared with national reference data.Results: 314 patients were identified (median age 33.2 [IQR 24.8-44.7], 40.8% women). The mean percent of predicted workload was 74.8 (±19.6) % without change across ages. In multivariable analysis, NYHA class I (odds ratio [OR]4.2, 95% confidence interval [CI]1.7-10.0) and higher physical activity level (>3 h/week) (OR 3.6, 95%CI 1.8-7.3) were positively associated with higher exercise capacity, while ongoing cardiovascular therapy (OR 0.4, 95%CI 0.2-0.7) and male sex (OR 0.3, 95%CI 0.2-0.6) were negatively associated with higher exercise capacity. Both exercise capacity (HR 0.96, 95%CI 0.93-0.98) and heart rate reserve (HR 0.96, 95%CI 0.94-0.98) were associated with mortality.Conclusions: In patients with repaired tetralogy of Fallot the exercise capacity was approximately 75% of expected, regardless of age. Patients with better NYHA class and high physical activity level had a higher exercise capacity. Low exercise capacity and low heart rate reserve were associated with higher mortality. Therefore, evaluating exercise capacity as part of follow up is of importance.
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