| 1. |
- Hansson, Lars-Anders, et al.
(författare)
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Food-chain length alters community responses to global change in aquatic systems
- 2013
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Ingår i: Nature Climate Change. - 1758-6798. ; 3:3, s. 228-233
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Tidskriftsartikel (refereegranskat)abstract
- Synergies between large-scale environmental changes, such as climate change(1) and increased humic content (brownification)(2), will have a considerable impact on future aquatic ecosystems. On the basis of modelling, monitoring and experimental data, we demonstrate that community responses to global change are determined by food-chain length and that the top trophic level, and every second level below, will benefit from climate change, whereas the levels in between will suffer. Hence, phytoplankton, and thereby algal blooms, will benefit from climate change in three-, but not in two-trophic-level systems. Moreover, we show that both phytoplankton (resource) and zooplankton (consumer) advance their spring peak abundances similarly in response to a 3 degrees C temperature increase; that is, there is no support for a consumer/resource mismatch in a future climate scenario. However, in contrast to other taxa, cyanobacteria-known as toxin-producing nuisance phytoplankton(3)-benefit from a higher temperature and humic content irrespective of the food-chain composition. Our results are mirrored in natural ecosystems. By mechanistically merging present food-chain theory with large-scale environmental and climate changes, we provide a powerful framework for predicting and understanding future aquatic ecosystems and their provision of ecosystem services and water resources.
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| 2. |
- Isaacs, John T., et al.
(författare)
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Tasquinimod Is an Allosteric Modulator of HDAC4 Survival Signaling within the Compromised Cancer Microenvironment
- 2013
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Ingår i: Cancer Research. - 1538-7445. ; 74:4, s. 1386-1399
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Tidskriftsartikel (refereegranskat)abstract
- Tasquinimod is an orally active antiangiogenic drug that is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer. However, the target of this drug has remained unclear. In this study, we applied diverse strategies to identify the histone deacetylase HDAC4 as a target for the antiangiogenic activity of tasquinimod. Our comprehensive analysis revealed allosteric binding (Kd 10-30 nmol/L) to the regulatory Zn2+ binding domain of HDAC4 that locks the protein in a conformation preventing HDAC4/N-CoR/HDAC3 complex formation. This binding inhibited colocalization of N-CoR/HDAC3, thereby inhibiting deacetylation of histones and HDAC4 client transcription factors, such as HIF-1 alpha, which are bound at promoter/enhancers where epigenetic reprogramming is required for cancer cell survival and angiogenic response. Through this mechanism, tasquinimod is effective as a monotherapeutic agent against human prostate, breast, bladder, and colon tumor xenografts, where its efficacy could be further enhanced in combination with a targeted thapsigargin prodrug (G202) that selectively kills tumor endothelial cells. Together, our findings define a mechanism of action of tasquinimod and offer a perspective on how its clinical activity might be leveraged in combination with other drugs that target the tumor microenvironment. Cancer Res; 73(4); 1386-99. (C) 2012 AACR.
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| 3. |
- Bjork, Anders Anker, et al.
(författare)
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Possible Late Pleistocene volcanic activity on Nightingale Island, South Atlantic Ocean, based on geoelectrical resistivity measurements, sediment corings and (14)C dating
- 2011
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Ingår i: GFF. - : Informa UK Limited. - 2000-0863 .- 1103-5897. ; 133:3-4, s. 141-147
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Tidskriftsartikel (refereegranskat)abstract
- Tristan da Cunha is a volcanic island group situated in the central South Atlantic. The oldest of these islands, Nightingale Island, has an age of about 18Ma. In the interior of the island, there are several wetlands situated in topographic depressions. The ages of these basins have been unknown, and their genesis has been debated. Aiming towards the reconstruction of the geomorphological history of these basins, we conducted geoelectrical resistivity measurements to map the subsurface topography, extracted peat and sediment cores and dated the onset of sedimentation applying the radiocarbon method. The irregular shapes of the basins and the lack of clear erosional features indicate that they are not eruption craters and were not formed by erosion. Instead, we regard them as morphological depressions formed between ridges of trachytic lava flows and domes at a late stage of the formation of the volcanic edifice. The onset of sedimentation within these basins appears to have occurred between 24 and 37 ka with the highest situated wetland yielding the highest ages. These ages are very young compared to the timing of the main phase of the formation of the island, implying volcanic activity on the island during the Late Pleistocene.
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| 4. |
- Kritzberg, Emma, et al.
(författare)
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Warming and browning of lakes: consequences for pelagic carbon metabolism and sediment delivery
- 2014
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070. ; 59:2, s. 325-336
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Tidskriftsartikel (refereegranskat)abstract
- 1. Thousands of lakes in the Northern Hemisphere are experiencing a continuous increase in water temperature and colour. While increasing temperature is an effect of climate change, several factors are suggested to drive the increasing water colour, including climate change, altered land use and reversed acidification. 2. In this mesocosm study, we study the effects on pelagic production and sedimentation of organic carbon from a 3 degrees C increase in temperature, a doubling of water colour and a combination of increased temperature and water colour. These manipulations correspond to the predicted development in water colour and temperature in northern temperate systems within the life time of the next generation. 3. The water and plankton communities in the mesocosms were taken from an oligohumic and mesotrophic lake, and the increase in water colour was achieved by the additions of water from a humic lake. The experiment ran from early March to late October. 4. In accordance with our predictions and previous cross-system analyses, net carbon production (NCP) and organic carbon sedimentation decreased in response to increasing water colour. 5. At odds with current theory, NCP and sedimentation increased in heated treatments, as not only respiration but also gross production increased in response to temperature. There were no synergistic effects between warming and browning. 6. These results imply that warming may enhance pelagic delivery of organic carbon to sediments. This could potentially offset a reduction in burial efficiency of organic carbon, which has been projected based on a positive relationship between carbon mineralisation in sediments and temperature.
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| 5. |
- Nyholm, Tufve, et al.
(författare)
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A national approach for automated collection of standardized and population-based radiation therapy data in Sweden
- 2016
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 119:2, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion.
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| 6. |
- Olsson, Anders, et al.
(författare)
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Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors
- 2010
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Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The orally active quinoline-3-carboxamide tasquinimod [ABR-215050; CAS number 254964-60-8), which currently is in a phase II-clinical trial in patients against metastatic prostate cancer, exhibits anti-tumor activity via inhibition of tumor angiogenesis in human and rodent tumors. To further explore the mode of action of tasquinimod, in vitro and in vivo experiments with gene microarray analysis were performed using LNCaP prostate tumor cells. The array data were validated by real-time semiquantitative reversed transcriptase polymerase chain reaction (sqRT-PCR) and protein expression techniques. Results: One of the most significant differentially expressed genes both in vitro and in vivo after exposure to tasquinimod, was thrombospondin-1 (TSP1). The up-regulation of TSP1 mRNA in LNCaP tumor cells both in vitro and in vivo correlated with an increased expression and extra cellular secretion of TSP1 protein. When nude mice bearing CWR-22RH human prostate tumors were treated with oral tasquinimod, there was a profound growth inhibition, associated with an up-regulation of TSP1 and a down-regulation of HIF-1 alpha protein, androgen receptor protein (AR) and glucose transporter-1 protein within the tumor tissue. Changes in TSP1 expression were paralleled by an anti-angiogenic response, as documented by decreased or unchanged tumor tissue levels of VEGF (a HIF-1 alpha down stream target) in the tumors from tasquinimod treated mice. Conclusions: We conclude that tasquinimod-induced up-regulation of TSP1 is part of a mechanism involving down-regulation of HIF1 alpha and VEGF, which in turn leads to reduced angiogenesis via inhibition of the "angiogenic switch", that could explain tasquinimods therapeutic potential.
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| 7. |
- Bennike, Ole, et al.
(författare)
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An Early Pleistocene interglacial deposit at Pingorsuit, North-West Greenland
- 2023
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Ingår i: Boreas. - : John Wiley & Sons. - 0300-9483 .- 1502-3885. ; 52:1, s. 27-41
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Tidskriftsartikel (refereegranskat)abstract
- At the Pingorsuit Glacier in North-West Greenland, an organic-rich deposit that had recently emerged from the retreating ice cap was discovered at an elevation of 480 m above sea level. This paper reports on macrofossil analyses of a coarse detritus gyttja and peaty soil, which occurred beneath a thin cover of till and glacifluvial deposits. The sediments contained remains of vascular plants, mosses, beetles, caddisflies, midges, bryozoans, sponges and other invertebrates. The flora includes black spruce, tree birch, boreal shrubs and wetland and aquatic taxa, which shows that mires, lakes and ponds were present in the area. We describe a new extinct waterwort species Elatine odgaardii. The fossils were deposited in a boreal environment with a mean July air temperature that was at least 9 degrees C higher than at present. The fossil assemblages show strong similarities with others from Greenland that have been assigned an Early Pleistocene age, and we suggest a similar age for the sediments found at the margin of the Pingorsuit Glacier. At the Pingorsuit Glacier in North-West Greenland, an organic-rich deposit was discovered at an elevation of 480 m above sea level. The sediments contained remains of vascular plants, mosses, beetles, caddisflies, midges, bryozoans, sponges and other invertebrates. The fossils were deposited in a boreal environment with a mean July air temperature that was at least 9 degrees C higher than at present.
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| 8. |
- Chakraborty, Paramita, et al.
(författare)
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Vesicular Location and Transport of S100A8 and S100A9 Proteins in Monocytoid Cells.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- We show here, by using surface biotinylation, followed by Western blotting or surface plasmon resonance analysis, that very low levels of S100A8 and/or S100A9 can be detected on the surface of THP-1 cells or freshly isolated human monocytes. This was supported by immune-electron microscopy where we observed membrane-associated expression of the proteins restricted to small patches. By using confocal microscopy we could determine that S100A8 and S100A9 protein in THP-1 cells or freshly isolated human monocytes was mostly present in vesicular structures. This finding was confirmed using immune-electron microscopy. Subcellular fractionation and confocal microscopy showed that these vesicular structures are mainly early endosomes and endolysosomes. Our subsequent studies showed that accumulation of S100A8 and S100A9 in the endolysosomal compartment is associated with induction of their release from the cells. Furthermore, an inhibitor of lysosomal activity could modulate the release of S100A8 and S100A9 in the extracellular milieu. Our current results suggest that the S100A8 and S100A9 proteins are primarily associated with certain kinds of cytosolic vesicles and may be secreted via an endolysosomal pathway.
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| 9. |
- Isma, Nazim, et al.
(författare)
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Does supervised exercise after deep venous thrombosis improve recanalization of occluded vein segments? A randomized study.
- 2007
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 23:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of the present study was to evaluate weather early supervised exercise improves recanalization of acute deep vein thrombosis (DVT) and reduces symptoms. Patients and methods From September 2001 to March 2004, of 381 patients, 72 eligible patients were included and with a mean age 54 +/- 14 years, 39 (52%) men with deep vein thrombosis ( DVT) proven with phlebography were randomized to: an exercise group (n = 36) receiving routine anticoagulation, class II compression stockings and additionally supervised exercise and a control group ( n = 36) receiving the same therapy but no exercise. Patients were followed-up during six months. Phlebography was scored initially and at six-months. Results There were at inclusion no differences between the two groups regarding age, body weight, body mass index (BMI), calf circumference of the affected leg, and overall quality of life estimated by visual analog scale ( VAS)-scale. In both groups there were significant reductions regarding calf circumference in the affected leg compared to the inclusion time, both at one-month ( P = 0.0012) and six month ( P = 0.0002) follow-up. The degree of recanalization of the affected venous segments was high and did not differ between groups. There were no recurrent DVT or pulmonary emboli or other treatment complications in any individual during the six-month follow-up period. Conclusions Early exercise did not acutely exacerbate the risk of complications in patients with DVT. No benefits of early exercise were seen regarding the degree of recanalization of the thrombi, or faster resolution of pain or swelling. Nevertheless, our study shows that early exercise/ambulation is safe in combination with anticoagulation and compression stockings for the majority of patients with DVT.
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| 10. |
- Kolsrud, Oscar, et al.
(författare)
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Dextran-based priming solution during cardiopulmonary bypass attenuates renal tubular injury-A secondary analysis of randomized controlled trial in adult cardiac surgery patients
- 2022
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- Background Acute kidney injury (AKI) is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In the present secondary analysis of a blinded randomized controlled trial, we evaluated the effects of a colloid-based versus a conventional crystalloid-based prime on tubular injury and postoperative renal function in patients undergoing cardiac surgery with CPB. Methods Eighty-four adult patients undergoing cardiac surgery with CPB were randomized to receive either a crystalloid- or colloid- (dextran 40) based CPB priming solution. The crystalloid solution was based on Ringer-Acetate plus mannitol. The tubular injury biomarker, N-acetyl-b-D-glucosaminidase (NAG), serum creatinine and diuresis were measured before, during and after CPB. The incidence of AKI was assessed according to the KDIGO criteria. Results The urinary-NAG/urinary-creatinine ratio rose in both groups during and after CPB, with a more pronounced increase in the crystalloid group (p = .038). One hour after CPB, the urinary-NAG/urinary-creatinine ratio was 88% higher in the crystalloid group (4.7 +/- 6.3 vs. 2.5 +/- 2.7, p = .045). Patients that received the dextran 40-based priming solution had a significantly lower intraoperative diuresis (p < .001) compared to the crystalloid group. The incidence of AKI was 18% in the colloid and 22% in the crystalloid group (p = .66). Postoperative serum creatinine did not differ between groups. Conclusions In patients undergoing cardiac surgery with CPB, colloid-based priming solution (dextran 40) induced less renal tubular injury compared to a crystalloid-based priming solution. Whether a colloid-based priming solution will improve renal outcome in high-risk cardiac surgery, or not, needs to be evaluated in future studies on higher risk cardiac surgery patients.
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