| 1. |
- Flowers, Sarah A., et al.
(författare)
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Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking
- 2020
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:47, s. 16023-16036
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Tidskriftsartikel (refereegranskat)abstract
- The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin's ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.
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| 2. |
- Luquez, Virginia, et al.
(författare)
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Natural phenological variation in aspen (Populus tremula) : the SwAsp collection
- 2008
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Ingår i: Tree Genetics & Genomes. - : SpringerLink. - 1614-2942 .- 1614-2950. ; 4, s. 279-292
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Tidskriftsartikel (refereegranskat)abstract
- The genus Populus is currently the main model system for genetic, genomic, and physiological research in trees. Phenotypic variation in aspen (Populus tremula) populations growing in different environments across Sweden is expected to reflect genetic variation that is important for local adaptation. To analyze such natural phenotypic and genetic variation, the Swedish Aspen (SwAsp) Collection was established. Trees were taken from 12 different populations across Sweden, from 56° to 66° latitude north and planted in two common gardens in Ekebo (55.9°N) and Sävar (63.4°N). Data related to phenological and growth traits were collected during the second year of growth. Some traits like the date of bud set and leaf area duration showed strong clinal variation patterns with latitude in both field trials, but the date of bud flush did not change along a latitudinal cline. The phenological traits showed moderate within-populations heritabilities, although growth traits showed weaker clinal patterns and lower heritabilities than the phenological traits. This research forms the starting point for the development of the SwAsp collection, a resource facilitating analysis of the natural genetic variation in aspen, the elucidation of the structure and dynamics of aspen populations, and the future identification of the genes controlling adaptive traits using association mapping of selected candidate genes.
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| 3. |
- Magnusson, Lisa U., 1975, et al.
(författare)
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Arachidonate 15-Lipoxygenase Type B Knockdown Leads to Reduced Lipid Accumulation and Inflammation in Atherosclerosis
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation in the vascular wall is important for development of atherosclerosis. We have shown previously that arachidonate 15-lipoxygenase type B (ALOX15B) is more highly expressed in human atherosclerotic lesions than in healthy arteries. This enzyme oxidizes fatty acids to substances that promote local inflammation and is expressed in lipid-loaded macrophages (foam cells) present in the atherosclerotic lesions. Here, we investigated the role of ALOX15B in foam cell formation in human primary macrophages and found that silencing of human ALOX15B decreased cellular lipid accumulation as well as proinflammatory cytokine secretion from macrophages. To investigate the role of ALOX15B in promoting the development of atherosclerosis in vivo, we used lentiviral shRNA silencing and bone marrow transplantation to knockdown mouse Alox15b gene expression in LDL-receptor-deficient (Ldlr(-/-)) mice. Knockdown of mouse Alox15b in vivo decreased plaque lipid content and markers of inflammation. In summary, we have shown that ALOX15B influences progression of atherosclerosis, indicating that this enzyme has an active proatherogenic role.
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| 4. |
- Åberg, Jan, 1977-, et al.
(författare)
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Pelagic and benthic net production of dissolved inorganic carbon in an unproductive subarctic lake
- 2007
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 52:3, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- 1. Both the pelagic and benthic net dissolved inorganic carbon (DIC) productions were measured in situ on four occasions from June to September 2004, in the unproductive Lake Diktar-Erik in subarctic Sweden. The stable isotopic signal (δ13C) of respired organic material was estimated from hypolimnion water data and data from a laboratory incubation using epilimnion water. 2. Both pelagic and benthic habitats were net heterotrophic during the study period, with a total net DIC production of 416 mg C m-2 day-1, of which the pelagic habitat contributed approximately 85%. The net DIC production decreased with depth both in the pelagic water and in the sediments, and most of the net DIC production occurred in the upper water column. 3. Temporal variations in both pelagic and benthic DIC production were small, although we observed a significant decrease in pelagic net DIC production after the autumn turnover. Water temperature was the single most important factor explaining temporal and vertical variations in pelagic DIC production. No single factor explained more than 10% of the benthic net DIC production, which probably was regulated by several interacting factors. 4. Pelagic DIC production, and thus most of the whole-lake net production of DIC, was mainly due to the respiration of allochthonous organic carbon. Stable isotope data inferred that nearly 100% of accumulated DIC in the hypolimnion water had an allochthonous carbon source. Similarly, in the laboratory incubation using epilimnion water, c. 85% of accumulated DIC was indicated to have an allochthonous organic carbon source.
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| 5. |
- Anand, Aseem, et al.
(författare)
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Assessing Radiographic Response to 223Ra with an Automated Bone Scan Index in Metastatic Castration-Resistant Prostate Cancer Patients
- 2020
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X .- 1535-5667. ; 61:5, s. 671-675
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Tidskriftsartikel (refereegranskat)abstract
- For effective clinical management of patients being treated with 223Ra, there is a need for radiographic response biomarkers to minimize disease progression and to stratify patients for subsequent treatment options. The objective of this study was to evaluate an automated bone scan index (aBSI) as a quantitative assessment of bone scans for radiographic response in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: In a multicenter retrospective study, bone scans from patients with mCRPC treated with monthly injections of 223Ra were collected from 7 hospitals in Sweden. Patients with available bone scans before treatment with 223Ra and at treatment discontinuation were eligible for the study. The aBSI was generated at baseline and at treatment discontinuation. The Spearman rank correlation was used to correlate aBSI with the baseline covariates: alkaline phosphatase (ALP) and prostate-specific antigen (PSA). The Cox proportional-hazards model and Kaplan-Meier curve were used to evaluate the association of covariates at baseline and their change at treatment discontinuation with overall survival (OS). The concordance index (C-index) was used to evaluate the discriminating strength of covariates in predicting OS. Results: Bone scan images at baseline were available from 156 patients, and 67 patients had both a baseline and a treatment discontinuation bone scan (median, 5 doses; interquartile range, 3-6 doses). Baseline aBSI (median, 4.5; interquartile range, 2.4-6.5) was moderately correlated with ALP (r = 0.60, P < 0.0001) and with PSA (r = 0.38, P = 0.003). Among baseline covariates, aBSI (P = 0.01) and ALP (P = 0.001) were significantly associated with OS, whereas PSA values were not (P = 0.059). After treatment discontinuation, 36% (24/67), 80% (54/67), and 13% (9/67) of patients demonstrated a decline in aBSI, ALP, and PSA, respectively. As a continuous variable, the relative change in aBSI after treatment, compared with baseline, was significantly associated with OS (P < 0.0001), with a C-index of 0.67. Median OS in patients with both aBSI and ALP decline (median, 134 wk) was significantly longer than in patients with ALP decline only (median, 77 wk; P = 0.029). Conclusion: Both aBSI at baseline and its change at treatment discontinuation were significant parameters associated with OS. The study warrants prospective validation of aBSI as a quantitative imaging response biomarker to predict OS in patients with mCRPC treated with 223Ra.
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| 6. |
- Ask, Jenny, 1976-, et al.
(författare)
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Terrestrial organic matter and light penetration : Effects on bacterial and primary production in lakes
- 2009
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Ingår i: Limnology and Oceanography. - : American Society of Limnology and Oceanography, Inc.. - 0024-3590 .- 1939-5590. ; 54:6, s. 2034-2040
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Tidskriftsartikel (refereegranskat)abstract
- We investigated productivity at the basal trophic level in 15 unproductive lakes in a gradient ranging from clear-water to brown-water (humic) lakes in northern Sweden. Primary production and bacterial production in benthic and pelagic habitats were measured to estimate the variation in energy mobilization from external energy sources (primary production plus bacterial production on allochthonous organic carbon) along the gradient. Clear-water lakes were dominated by autotrophic energy mobilization in the benthic habitat, whereas humic lakes were dominated by heterotrophic energy mobilization in the pelagic habitat. Whole-lake (benthic + pelagic) energy mobilization was negatively correlated to the light-extinction coefficient, which was determined by colored terrestrial organic matter in the lake water. Thus, variation in the concentration of terrestrial organic matter and its light-absorbing characteristics exerts strong control on the magnitude, as well as on the processes and pathways, of energy mobilization in unproductive lakes. We suggest that unproductive lakes in general are sensitive to input of terrestrial organic matter because of its effects on basal energy mobilization in both benthic and pelagic habitats.
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| 7. |
- Ask, Jenny, 1976-, et al.
(författare)
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Whole-lake estimates of carbon flux through algae and bacteria in benthic and pelagic habitats of clear-water lakes
- 2009
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Ingår i: Ecology. - Washington, DC, USA : Ecological Society of America. - 0012-9658 .- 1939-9170. ; 90:7, s. 1923-1932
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Tidskriftsartikel (refereegranskat)abstract
- This study quantified new biomass production of algae and bacteria in both benthic and pelagic habitats of clear-water lakes to contrast how carbon from the atmosphere and terrestrial sources regulates whole-lake metabolism. We studied four small unproductive lakes in subarctic northern Sweden during one summer season. The production of new biomass in both benthic and pelagic habitats was calculated as the sum of autotrophic production by algae and heterotrophic production by bacteria using allochthonous organic carbon (OC). Whole-lake production of new biomass was dominated by the benthic habitat (86% +/- 4% [mean +/- SD]) and by primary production (77% +/- 9%). Still, heterotrophic bacteria fueled by allochthonous OC constituted a significant portion of the new biomass production in both benthic (19% +/- 11%) and pelagic habitats (51% +/- 24%). In addition, overall net production (primary production minus respiration) was close to zero in the benthic habitats but highly negative (-163 +/- 81 mg C.m(-2).d(-1)) in pelagic regions of all lakes. We conclude (1) that allochthonous OC supported a significant part of total production of new biomass in both pelagic and benthic habitats, (2) that benthic habitats dominated the whole-lake production of new biomass, and (3) that respiration and net CO2 production dominated the carbon flux of the pelagic habitats and biomass production dominated the benthic carbon flux. Taken together, these findings suggest that previous investigations have greatly underestimated the productivity of clear-water lakes when benthic autotrophic production and metabolism of allochthonous OC have not been measured.
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| 8. |
- Ask, Per, 1978-, et al.
(författare)
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Competition mediated coexistence of invading intermediate consumer, ninespine stickleback, and a resident omnivorous top predator, Arctic char
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Climate change results in changes in the geographical distribution of species. Species invasion success into a new area is dependent both on the dispersal ability of species as well as the strength and identity of biotic interactions between resident and invading species. Coexistence in intraguild predation (IGP) systems depends on the relative strength of predation and competition interactions which in turn are temperature dependent. We investigated the effects of introducing an intermediate consumer, ninespine stickleback (Pungitius pungitius), into allopatric populations of the omnivorous top predator Arctic char (Salvelinus alpinus). Introductions were performed in lakes with different climate regimes, two tundra lakes and two forest lakes that differed in average summer temperatures with 1.4 ± 0.5 ºC (average ± 1SD). We found that sticklebacks were able to invade and increase in density in both tundra and forest lakes. Sticklebacks had strong negative effects on resource densities which also was reflected in a decreased growth of small char. Increasing stickleback density had a positive effect on growth of large adults and on the maximum size of char. We conclude that stickleback presence is not limited by biological interactions in these systems but rather by dispersion ability. We suggest that the size dependency in the response of char to the invasion of sticklebacks is fundamental for the successful invasion of sticklebacks, and that size dependent interactions including cannibalism play important roles for coexistence in natural IGP-systems.
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| 9. |
- Ask, Per, 1978-, et al.
(författare)
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Temperature mediated effects on top consumer populations in subarctic lakes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The effects of temperature on top consumer populations in subarctic lake communities were studied by contrasting two lake pairs in different climate regimes: one pair on the low alpine tundra and one pair in the subalpine birch forest. We measured zooplankton and macroinvertebrate biomasses over the season and estimated population density and size structure of the top consumer Arctic char (Salvelinus alpinus). Furthermore, we modelled char growth using literature data on temperature dependent search rate, handling time and metabolic demands. The forest lakes were warmer than the tundra lakes. Char in the forest lakes were larger and had a higher individual growth compared to char in the tundra lakes, while population density and biomasses of char were not different between the forest and the tundra lakes. There were no differences in macroinvertebrate and zooplankton resource levels available for char between lake pairs. Our modeling of char growth revealed that higher temperature increased growth of char at the observed resource densities, suggesting that the higher temperature in the forest lakes was primarily the cause of the higher growth of char in these lakes. We suggest that cannibalism in char may regulate char recruitment and thereby population density and biomass of char leading to effects of increasing temperature on consumer biomass and consumer individual growth different from what is expected in pure consumer-resource systems. Our results emphasize the importance of feedbacks within ecosystems when addressing effects of climate change and increasing temperature on lake communities.
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| 10. |
- Bandaru, Sashidar, et al.
(författare)
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Targeting filamin A reduces macrophage activity and atherosclerosis. : Filamin A in atherogenesis
- 2019
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Ingår i: Circulation. - 1524-4539. ; 140:1, s. 67-79
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Tidskriftsartikel (refereegranskat)abstract
- The actin-binding protein FLNA (filamin A) regulates signal transduction important for cell locomotion, but the role of macrophage-specific FLNA during atherogenesis has not been explored.We analyzed FLNA expression in human carotid atherosclerotic plaques by immunofluorescence. We also produced mice with Flna-deficient macrophages by breeding conditional Flna-knockout mice ( Flna o/fl) with mice expressing Cre from the macrophage-specific lysosome M promoter ( LC). Atherosclerosis in vivo was studied by transplanting bone marrow from male Flna o/fl/ LC mice to atherogenic low-density lipoprotein receptor-deficient ( Ldlr-/-) mice; and by infecting Flna o/fl and Flna o/fl/ LC mice with AdPCSK9 (adenoviral vector overexpressing proprotein convertase subtilisin/kexin type 9). Furthermore, C57BL/6 mice were infected with AdPCSK9 and then treated with the calpain inhibitor calpeptin to inhibit FLNA cleavage.We found that macrophage FLNA expression was higher in advanced than in intermediate human atherosclerotic plaques. Flna o/fl/ LC macrophages proliferated and migrated less than controls; expressed lower levels of phosphorylated AKT and ERK1/2; exhibited reduced foam cell formation and lipid uptake; and excreted more lipids. The deficiency of Flna in macrophages markedly reduced the size of aortic atherosclerotic plaques in both Ldlr-/-BMT: Flnao/fl/LC and AdPCSK9-infected Flna o/fl/ LC mice. Intima/media ratios and numbers of CD68-positive macrophages in atherosclerotic plaques were lower in Flna-deficient mice than in control mice. Moreover, we found that STAT3 interacts with a calpain-cleaved carboxyl-terminal fragment of FLNA. Inhibiting calpain-mediated FLNA cleavage with calpeptin in macrophages reduced nuclear levels of phosphorylated STAT3, interleukin 6 secretion, foam cell formation, and lipid uptake. Finally, calpeptin treatment reduced the size of atherosclerotic plaques in C57BL/6 mice infected with AdPCSK9.Genetic inactivation of Flna and chemical inhibition of calpain-dependent cleavage of FLNA impaired macrophage signaling and function, and reduced atherosclerosis in mice, suggesting that drugs targeting FLNA may be useful in the treatment of atherosclerosis.
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