| 1. |
- Berg, Björn, et al.
(författare)
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Late stage pine litter decomposition : Relationship to litter N, Mn, and acid unhydrolyzable residue (AUR) concentrations and climatic factors
- 2015
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 358, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to evaluate relationships between decomposition rates of Scots pine (Pinus sylvestris) and lodgepole pine (Pinus contorta var. contorta) needle litter in the late stage of decomposition (>30% accumulated mass loss), and the progressively changing concentrations of manganese (Mn), nitrogen (N), and acid unhydrolyzable residue (AUR), as well as mean annual temperature (MAT) and mean annual precipitation (MAP). Using available long-term decomposition studies on pine needle litter in a climate gradient in Sweden, we calculated annual mass loss and related to concentrations of Mn, N, and AUR at the start of each one-year period as well as to MAT and MAP. We investigated these relationships for (i) all data on annual mass loss combined and (ii) annual mass loss for five different decomposition categories as defined by accumulated mass loss. We found highly significant, negative, and dominant relationships between annual mass loss and N (R2=0.39) and AUR (R2=0.39), a slight but significant positive relationship to Mn (R2=0.08) and a significant negative relationship to MAT (R2=0.06). The relationships were dynamic, and changed with accumulated mass loss. The rate-dampening effect of N decreased to be a rate-enhancing effect at c. 60-80% accumulated mass loss. A similar trend was found for AUR, becoming rate-enhancing at 70-80% accumulated mass loss. For Scots pine needle litter the effect of MAT on mass loss decreased with increasing accumulated mass loss and changed to a rate-dampening effect at c. 50-70% accumulated mass loss. Mn showed a stimulating effect on mass loss rate in all categories whereas MAP showed no effect in this mainly boreal climatic gradient. The current approach indicates a method for detailed studies of rate-regulating factors for litter decomposition.
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| 2. |
- Gerdle, Björn, et al.
(författare)
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The importance of emotional distress, cognitive behavioural factors and pain for life impact at baseline and for outcomes after rehabilitation - a SQRP study of more than 20,000 chronic pain patients
- 2019
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 19:4, s. 693-711
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims Although literature concerning chronic pain patients indicates that cognitive behavioural variables, specifically acceptance and fear of movement/(re)injury, are related to life impact, the relative roles of these factors in relation to pain characteristics (e.g. intensity and spreading) and emotional distress are unclear. Moreover, how these variables affect rehabilitation outcomes in different subgroups is insufficiently understood. This study has two aims: (1) to investigate how pain, cognitive behavioural, and emotional distress variables intercorrelate and whether these variables can regress aspects of life impact and (2) to analyse whether these variables can be used to identify clinically meaningful subgroups at baseline and which subgroups benefit most from multimodal rehabilitation programs (MMRP) immediately after and at 12-month follow-up. Methods Pain aspects, background variables, psychological distress, cognitive behavioural variables, and two life impact variables were obtained from the Swedish Quality Registry for Pain Rehabilitation (SQRP) for chronic pain patients. These data were analysed mainly using advanced multivariate methods. Results The study includes 22,406 chronic pain patients. Many variables, including acceptance variables, showed important contributions to the variation in clinical presentations and in life impacts. Based on the statistically important variables considering the clinical presentation, three clusters/subgroups of patients were identified at baseline; from the worst clinical situation to the relatively good situation. These clusters showed significant differences in outcomes after participating in MMRP; the subgroup with the worst situation at baseline showed the most significant improvements. Conclusions Pain intensity/severity, emotional distress, acceptance, and life impacts were important for the clinical presentation and were used to identify three clusters with marked differences at baseline (i.e. before MMRP). Life impacts showed complex relationships with acceptance, pain intensity/severity, and emotional distress. The most significant improvements after MMRP were seen in the subgroup with the lowest level of functioning before treatment, indicating that patients with complex problems should be offered MMRP. Implications This study emphasizes the need to adopt a biopsychosocial perspective when assessing patients with chronic pain. Patients with chronic pain referred to specialist clinics are not homogenous in their clinical presentation. Instead we identified three distinct subgroups of patients. The outcomes of MMRP appears to be related to the clinical presentation. Thus, patients with the most severe clinical presentation show the most prominent improvements. However, even though this group of patients improve they still after MMRP show a complex situation and there is thus a need for optimizing the content of MMRP for these patients. The subgroup of patients with a relatively good situation with respect to pain, psychological distress, coping and life impact only showed minor improvements after MMRP. Hence, there is a need to develop other complex interventions for them.
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| 3. |
- Gerdle, Björn, et al.
(författare)
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Who benefits from multimodal rehabilitation - an exploration of pain, psychological distress, and life impacts in over 35,000 chronic pain patients identified in the Swedish Quality Registry for Pain Rehabilitation
- 2019
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Ingår i: Journal of Pain Research. - : DOVE Medical Press Ltd.. - 1178-7090. ; 12, s. 891-908
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic pain patients frequently suffer from psychological symptoms. There is no consensus concerning the prevalence of severe anxiety and depressive symptoms and the strength of the associations between pain intensity and psychological distress. Although an important aspect of the clinical picture is understanding how the pain condition impacts life, little is known about the relative importance of pain and psychological symptoms for individual's life impact. The aims of this study were to identify subgroups of pain patients; to analyze if pain, psychological distress, and life impact variables influence subgrouping; and to investigate how patients in the subgroups benefit from treatments.Methods: Background variables, pain aspects (intensity/severity and spreading), psychological distress (depressive and anxiety symptoms), and two life impact variables (pain interference and perceived life control) were obtained from the Swedish Quality Registry for Pain Rehabilitation for chronic pain patients and analyzed mainly using advanced multivariate methods.Results: Based on >35,000 patients, 35%-40% had severe anxiety or depressive symptoms. Severe psychological distress was associated with being born outside Europe (21%-24% vs 6%-8% in the category without psychological distress) and low education level (20.7%-20.8% vs 26%-27% in the category without psychological distress). Dose relationships existed between the two psychological distress variables and pain aspects, but the explained variances were generally low. Pain intensity/severity and the two psychological distress variables were significantly associated (R2=0.40-0.48; P>0.001) with the two life impact variables (pain interference and life control). Two subgroups of patients were identified at baseline (subgroup 1: n=15,901-16,119; subgroup 2: n=20,690-20,981) and the subgroup with the worst situation regarding all variables participated less in an MMRP (51% vs 58%, P<0.001) but showed the largest improvements in outcomes.Conclusion: The results emphasize the need to assess both pain and psychological distress and not take for granted that pain involves high psychological stress in the individual case. Not all patients benefit from MMRP. A better matching between common clinical pictures and the content of MMRPs may help improve results. We only partly found support for treatment resistance in patients with psychological distress burden.
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| 4. |
- Berg, Björn, 1943-, et al.
(författare)
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Magnesium dynamics in decomposing foliar litter - a synthesis
- 2021
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Ingår i: Geoderma. - : Elsevier. - 0016-7061 .- 1872-6259. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- We synthesized available data for magnesium (Mg) dynamics in newly shed and decomposing foliar litter of mainly pine (Pinus) species, Norway spruce (Picea abies), and birch (Betula) species. Using original, measured data from 40 stands organized in climatic gradients we intended to determine patterns of Mg concentration and net release vs accumulated mass loss of the litter. This synthesis is likely the first synthesis of Mg dynamics in decomposing litter.In paired stands, litter of both Norway spruce and lodgepole pine (Pinus contorta) had higher Mg concentrations than Scots pine (Pinus silvestris), with concentrations in Norway spruce litter even twice as high.In decomposing litter, Mg concentrations followed a quadratic (X2-X) function vs accumulated mass loss and consequently had minima, different for Norway spruce and Scots pine litter. Out of 68 decomposition studies 53 gave minimum concentration. The Mg minimum concentration during decomposition was positively related to initial Mg concentration for Scots pine and Scots pine plus lodgepole pine but not for Norway spruce. The increase in concentration suggests that after the minimum Mg was temporarily limiting.For Norway spruce litter there was a relationship between minimum concentration of Mg and the limit value. There was no such relationship for Scots pine and not for the combined pine data.Magnesium net release started directly after the incubation and was linear to accumulated mass loss of litter, giving a slope coefficient (release rate) for each study. The net release rate was linear to initial Mg concentration and all studies combined gave a negative linear relationship.
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| 5. |
- Funa, Nina, et al.
(författare)
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Interdependent fibroblast growth factor and activin A signaling promotes the expression of endodermal genes in differentiating mouse embryonic stem cells expressing Src Homology 2-domain inactive Shb
- 2008
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Ingår i: Differentiation. - : Elsevier BV. - 0301-4681 .- 1432-0436. ; 76:5, s. 443-453
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms controlling endodermal development during stem cell differentiation have been only partly elucidated, although previous studies have suggested the participation of fibroblast growth factor (FGF) and activin A in these processes. Shb is a Src homology 2 (SH2) domain-containing adapter protein that has been implicated in FGF receptor 1 (FGFR1) signaling. To study the putative crosstalk between activin A and Shb-dependent FGF signaling in the differentiation of endoderm from embryonic stem (ES) cells, embryoid bodies (EBs) derived from mouse ES cells overexpressing wild-type Shb or Shb with a mutated SH2 domain (R522K-Shb) were cultured in the presence of activin A. We show that expression of R522K-Shb results in up-regulation of FGFR1 and FGF2 in EBs. Addition of activin A to the cultures enhances the expression of endodermal genes primarily in EBs expressing mutant Shb. Inhibition of FGF signaling by the addition of the FGFR1 inhibitor SU5402 completely counteracts the synergistic effects of R522K-Shb and activin A. In conclusion, the present results suggest that expression of R522K-Shb enhances certain signaling pathways downstream of FGF and that an interplay between FGF and activin A participates in ES cell differentiation to endoderm.
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| 6. |
- Funa, Nina S, et al.
(författare)
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Dysfunctional microvasculature as a consequence of shb gene inactivation causes impaired tumor growth
- 2009
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 69:5, s. 2141-2148
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Tidskriftsartikel (refereegranskat)abstract
- Shb (Src homology 2 protein B) is an adapter protein downstream of the vascular endothelial growth factor receptor receptor-2 (VEGFR-2). Previous experiments have suggested a role for Shb in endothelial cell function. Recently, the Shb gene was inactivated and Shb null mice were obtained on a mixed genetic background, but not on C57Bl6 mice. The present study was performed to address endothelial function in the Shb knockout mouse and its relevance for tumor angiogenesis. Tumor growth was retarded in Shb mutant mice, and this correlated with decreased angiogenesis both in tumors and in Matrigel plugs. Shb null mice display an abnormal endothelial ultrastructure in liver sinusoids and heart capillaries with cytoplasmic extensions projecting toward the lumen. Shb null heart VE-cadherin staining was less distinct than that of control heart, exhibiting in the former case a wavy and punctuate pattern. Experiments on isolated endothelial cells suggest that these changes could partly reflect cytoskeletal abnormalities. Vascular permeability was increased in Shb null mice in heart, kidney, and skin, whereas VEGF-stimulated vascular permeability was reduced in Shb null mice. It is concluded that Shb plays an important role in maintaining a functional vasculature in adult mice, and that interference with Shb signaling may provide novel means to regulate tumor angiogenesis.
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| 7. |
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| 8. |
- Jonsson, Sofi, et al.
(författare)
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Terrestrial discharges mediate trophic shifts and enhance methylmercury accumulation in estuarine biota
- 2017
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Ingår i: Science Advances. - : American association for the advancement of science. - 2375-2548. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- The input of mercury (Hg) to ecosystems is estimated to have increased two- to fivefold during the industrial era, and Hg accumulates in aquatic biota as neurotoxic methylmercury (MeHg). Escalating anthropogenic land use and climate change are expected to alter the input rates of terrestrial natural organic matter (NOM) and nutrients to aquatic ecosystems. For example, climate change has been projected to induce 10 to 50% runoff increases for large coastal regions globally. A major knowledge gap is the potential effects on MeHg exposure to biota following these ecosystem changes. We monitored the fate of five enriched Hg isotope tracers added to mesocosm scale estuarine model ecosystems subjected to varying loading rates of nutrients and terrestrial NOM. We demonstrate that increased terrestrial NOM input to the pelagic zone can enhance the MeHg bioaccumulation factor in zooplankton by a factor of 2 to 7 by inducing a shift in the pelagic food web from autotrophic to heterotrophic. The terrestrial NOM input also enhanced the retention of MeHg in the water column by up to a factor of 2, resulting in further increased MeHg exposure to pelagic biota. Using mercury mass balance calculations, we predict that MeHg concentration in zooplankton can increase by a factor of 3 to 6 in coastal areas following scenarios with 15 to 30% increased terrestrial runoff. The results demonstrate the importance of incorporating the impact of climate-induced changes in food web structure on MeHg bioaccumulation in future biogeochemical cycling models and risk assessments of Hg.
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| 9. |
- Mokhtari, Dariush, et al.
(författare)
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Increased Hsp70 expression attenuates cytokine-induced cell death in islets of Langerhans from Shb knockout mice
- 2009
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 387:3, s. 553-557
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes may depend on cytokine-induced beta-cell death and therefore the current investigation was performed in order to elucidate this response in Shb-deficient islets. A combination of interleukin-1beta and interferon-gamma caused a diminished beta-cell death response in Shb null islets. Furthermore, the induction of an unfolded protein response (UPR) by adding cyclopiazonic acid did not increase cell death in Shb-deficient islets, despite simultaneous expression of UPR markers. The heat-shock protein Hsp70 was more efficiently induced in Shb knockout islets, providing an explanation for the decreased susceptibility of Shb-deficient islets to cytokines. It is concluded that islets deficient in the Shb protein are less susceptible to cytotoxic conditions, and that this partly depends on their increased ability to induce Hsp70 under such circumstances. Interference with Shb signaling may provide means to improve beta-cell viability under conditions of beta-cell stress.
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| 10. |
- Wang, Baolin, et al.
(författare)
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Biogeochemical influences on net methylmercury formation proxies along a peatland chronosequence
- 2021
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier. - 0016-7037 .- 1872-9533 .- 0046-564X. ; 308, s. 188-203
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Tidskriftsartikel (refereegranskat)abstract
- A geographically constrained chronosequence of peatlands divided into three age classes (young, intermediate and old) was used to explore the role of biogeochemical influences, including electron donors and acceptors as well as chemical speciation of inorganic mercury (Hg(II)), on net formation of methylmercury (MeHg) as approximated by the fraction of MeHg to total mercury (THg) in the peat soil. We hypothesized that removing vascular plants would reduce availability of electron donors and thus net MeHg formation. However, we found no effect of the vascular plant removal. The sum of the potential electron donors (acetate, lactate, propionate and oxalate), the electron donation proxy organic C/Organic N, and the potential electron acceptors (Fe(III), Mn and sulfate) in porewater all showed significant correlations with the net MeHg formation proxies in peat soil (MeHg concentration and %MeHg of THg). Thus differences in both electron donor and acceptor availability may be contributing to the pattern of net MeHg formation along the chronosequence. In contrast, Hg(II) concentrations in peat porewater showed small differences along the gradient. A chemical speciation model successfully predicted the solubility of Hg and MeHg in the porewater. The modeling pointed to an enhanced concentration of Hg-polysulfide species in the younger peatlands as a potential factor behind increased Hg(II) solubility and methylation in the more nutrient-rich peatlands. This work contributes to the understanding of Hg and MeHg cycling in peatlands which can help guide mitigation measures to reduce aquatic MeHg biomagnification in peatland dominated landscapes.
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| 11. |
- Wang, Baolin, et al.
(författare)
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Opposing spatial trends in methylmercury and total mercury along a peatland chronosequence trophic gradient
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 718
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Tidskriftsartikel (refereegranskat)abstract
- Peatlands are abundant elements of boreal landscapes where inorganic mercury (IHg) can be transformed into bioaccumulating and highly toxic methylmercury (MeHg). We studied fifteen peatlands divided into three age lasses (young, intermediate and old) along a geographically constrained chronosequence to determine the role of biogeochemical factors and nutrient availability in controlling the formation of MeHg. In the 10 cm soil layer just below the average annual growing season water table, concentrations of MeHg and %MeHg (of total Hg) were higher in younger, more mesotrophic peatlands than in older, more oligotrophic peatlands. In contrast, total mercury (THg) concentrations were higher in the older peatlands. Partial least squares (PLS) analysis indicates that the net MeHg production was positively correlated to trophic demands of vegetation and an increased availability of potential electron acceptors and donors for Hg methylating microorganisms. An important question for further studies will be to elucidate why there is less THg in the younger peatlands compared to the older peatlands, even though the age of the superficial peat itself is similar for all sites. We hypothesize that ecosystem features which enhance microbial processes involved in Hg methylation also promote Hg reduction that makes previously deposited Hg more available for evasion back to the atmosphere.
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| 12. |
- Welsh, Michael, et al.
(författare)
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The role of the Src Homology-2 domain containing protein B (SHB) in β cells
- 2015
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Ingår i: Journal of Molecular Endocrinology. - 0952-5041 .- 1479-6813. ; 56:1, s. R21-R31
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Forskningsöversikt (refereegranskat)abstract
- This review will describe the SH2-domain signaling protein Src Homology-2 domaincontaining protein B (SHB) and its role in various physiological processes relating inparticular to glucose homeostasis andbcell function. SHB operates downstream of severaltyrosine kinase receptors and assembles signaling complexes in response to receptoractivation by interacting with other signaling proteins via its other domains (proline-rich,phosphotyrosine-binding and tyrosine-phosphorylation sites). The subsequent responsesare context-dependent. Absence ofShbin mice has been found to exert effects onhematopoiesis, angiogenesis and glucose metabolism. Specifically, first-phase insulinsecretion in response to glucose was impaired and this effect was related to alteredcharacteristics of focal adhesion kinase activation modulating signaling through Akt, ERK,bcatenin and cAMP. It is believed that SHB plays a role in integrating adaptive responses tovarious stimuli by simultaneously modulating cellular responses in different cell-types, thusplaying a role in maintaining physiological homeostasis
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| 13. |
- Welsh, Michael, et al.
(författare)
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The tyrosine kinase FRK/RAK participates in cytokine-induced islet cell cytotoxicity
- 2004
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 382, s. 261-268
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Tidskriftsartikel (refereegranskat)abstract
- Hallmarks of the inflammatory process in Type I diabetes are macrophage activation, local release of b-cell-toxic cytokines and infiltration of cytotoxic T lymphocytes. We have observed recently that mice overexpressing active FRK (fyn-related kinase)/RAK (previously named GTK/Bsk/IYK, where GTK stands for gut tyrosine kinase, Bsk for b-cell Src-homology kinase and IYK for intestinal tyrosine kinase) in b-cells exhibit increased susceptibility to b-cell-toxic events, and therefore, we now attempt to find a more precise role for FRK/RAK in these processes. Phosphopeptide mapping of baculovirus-produced mouse FRK/RAK revealed an autophosphorylation pattern compatible with Tyr-394 being the main site. No evidence for in vitro phosphorylation of the C-terminal regulatory sites Tyr-497 and Tyr-504 was obtained, nor was there any indication of in vitro regulation of FRK/RAK kinase activity. Screening a panel of known tyrosine kinase inhibitors for their ability to inhibit FRK/RAK revealed several compounds that inhibited FRK/RAK, with a potency similar to that reported for their ability to inhibit other tyrosine kinases. Cytokine-induced islet toxicity was reduced in islets isolated from FRK/RAK knockout mice and this occurred without effects on the production of nitric oxide. Addition of the nitric oxide inhibitor nitroarginine to FRK/RAK knockout islets exposed to cytokines decreased cell death to a basal level. In normal islets, cytokine-induced cell death was inhibited by the addition of two FRK/RAK inhibitors, SU4984 and D-65495, or by transfection with short interfering RNA against FRK/RAK. It is concluded that FRK/RAK contributes to cytokine-induced b-cell death, and inhibition of this kinase could provide means to suppress b-cell destruction in Type I diabetes.
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| 14. |
- Åkerblom, Björn, et al.
(författare)
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A role of FRK in regulation of embryonal pancreatic beta cell formation
- 2007
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 270:1-2, s. 73-78
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Tidskriftsartikel (refereegranskat)abstract
- The fyn-related-kinase (FRK) is a non-receptor tyrosine kinase expressed in various tissues, and among them, is the islets of Langerhans. The role of FRK in pancreatic beta cells has been addressed by studies of knockout or FRK transgenic mice. These experiments have shown that FRK overexpression in beta cells leads to an increased susceptibility to the beta cell toxin streptozotocin and to cytotoxic cytokines, suggesting that FRK may participate in events leading to beta cell destruction. However, these mice also exhibit an increased relative beta cell volume and increased beta cell replication following partial pancreatectomy, suggesting a positive role for FRK in the regulation of beta cell number as well. To further assess the significance of FRK for beta cell replication, we studied the beta cell area and islet cell replication in FRK null mice. We currently observed that the FRK knockout mouse showed no difference in the insulin positive cell area or in the percentage of Ki67-stained proliferating islet cells at adulthood, when compared to wild-type control. In addition, adult FRK(-/-) mice performed normally when subjected to an intravenous glucose tolerance test. To elucidate whether FRK affects pancreatic beta cell number during embryogenesis and shortly after birth, pancreata were collected from FRK(-/-) mice at these stages. Histological analysis of insulin stained pancreatic sections showed that the insulin positive cell area in FRK(-/-) mice was reduced at embryonal day 15 and at birth to 31 and 70% of that of wild-type mice, respectively. FRK(-/-) pancreas weight on day 1 neonatally was similar to that of the control, indicating that the obtained results were not due to altered pancreatic growth. Taken together, these results show that FRK affects beta cell number during embryogenesis and early in life, but is probably redundant for beta cell number and function in adult animals under normal conditions.
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| 15. |
- Åkerblom, Björn, 1976-
(författare)
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Frk/Shb Signalling in Pancreatic Beta-cells : Roles in Islet Function, Beta-cell Development and Survival as Implicated in Mouse Knockout Models
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The adaptor protein Shb and the non-receptor tyrosine kinase Frk have been implicated in intracellular signalling in insulin-producing beta cells. In this thesis, knockout mice are used to further elucidate the role of Shb and Frk for beta cell number, cytokine-induced cell death, and glucose homeostasis. In addition, the effect of Shb deficiency upon tumour growth is studied in a mouse model of endogenous tumourigenesis. Previously, overexpression of Frk has been associated with increased beta cell replication, and increased susceptibility to cytokine induced beta cell destruction. To test whether Frk has a non-redundant role in regulating beta cell mass, beta cell number in Frk-/- mice was assessed at different stages of life. The results showed that Frk is involved in regulating beta cell number during embryonal and early postnatal life, but is probably redundant in the adult. An earlier study had suggested that Shb participates in cytokine-induced beta cell death, a model of autoimmune diabetes. To test this further, Shb-/- islets were exposed to cytokines, or to an ER-stress inducing agent. Shb knockout islets exhibited decreased cell death, and this effect appeared to be independent of NO, JNK, p38 MAP kinase, FAK and c-Abl, but may involve an augmented induction of Hsp70. Furthermore, glucose homeostasis in Shb-/- mice was impaired, with elevated basal blood sugar concentration and reduced glucose-induced insulin secretion. Previously Shb deficient mice had showed an impaired ability to sustain growth of implanted tumour cells, due to reduced angiogenesis. Tumour growth and angiogenesis were here assessed in an inheritable tumour model. Shb deficient mice exhibited fewer tumours, and reduced vessel density in small tumours, indicating impaired angiogenesis. However, a few large tumours developed in Shb-/- mice, suggesting that tumours can escape the angiogenic restriction caused by the absence of Shb.
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| 16. |
- Åkerblom, Björn, et al.
(författare)
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Heterogeneity among RIP-Tag2 insulinomas allows vascular endothelial growth factor-A independent tumor expansion as revealed by studies in Shb mutant mice : implications for tumor angiogenesis
- 2012
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 6:3, s. 333-346
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Tidskriftsartikel (refereegranskat)abstract
- The Shb adapter protein is a signaling intermediate that operates downstream of vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells. The Shb knockout mouse displays a dysfunctional microvasculature and impaired growth of subcutaneously implanted tumor cells. We decided to investigate tumor growth and angiogenesis in the absence of Shb in an inheritable tumor model, the RIP-Tag2 mouse, which produces insulinomas in a manner highly dependent on de novo angiogenesis. We observed a reduced tumor incidence and burden in both RIP-Tag2 Shb-/- and RIP-Tag2 Shb+/- mice. This correlated with a reduced microvascular density, measured as percentage of insulinoma area positive for CD31 staining, and altered vascular morphology. However, treatment with a VEGF-A blocking antibody was without effect on the Shb mutant tumor volume whereas it significantly inhibited tumor volume in the wild-type mice, suggesting that in mice with reduced Shb expression tumor angiogenesis was primarily sustained by VEGF-A independent pathway(s). This notion was further substantiated by gene expression analysis of angiogenic markers showing reduced VEGF-A expression in Shb deficient tumors. Considerable heterogeneity with respect to the gene expression profiles of other angiogenic markers and the signal-transduction characteristics was observed between different tumors, suggesting that multiple “rescue” pathways could be operating. The numbers of invasive tumors or metastases were unchanged in the Shb mutant. It is concluded that the Shb mutant background reduces tumor frequency by chronically suppressing VEGF-A dependent angiogenesis. However, VEGF-A independent angiogenesis supports a significant degree of tumor expansion in Shbdeficient mice, indicating heterogeneity in the mechanisms by which tumor expansion is promoted. Interference with Shb signaling may provide novel means for future cancer therapy.
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| 17. |
- Åkerblom, Björn, et al.
(författare)
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Impaired glucose homeostasis in Shb-/- mice
- 2009
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Ingår i: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 203:2, s. 271-279
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Tidskriftsartikel (refereegranskat)abstract
- Src homology 2 domain-containing protein B (SHB) is an adapter protein involved in the regulation of beta-cell and endothelial cell function. We have recently obtained the Shb knockout mouse, and consequently, the aim of this study was to assess the effect of Shb deletion upon beta-cell function and blood glucose homeostasis. Shb-/- mice display an elevated basal blood glucose concentration, and this increase is maintained during insulin challenge in insulin sensitivity tests. To assess glucose-induced insulin secretion, pancreata were perfused, and it was observed that Shb-/- first phase insulin secretion was blunted during glucose stimulation. Gene expression of Shb-/- islets shortly after isolation was altered, with increased pancreatic and duodenal homeobox gene-1 (Pdx1) gene expression and reduced expression of Vegf-A. Islet culture normalized Pdx1 gene expression. The microvascular density of the Shb-/- islets was reduced, and islet capillary endothelial cell morphology was changed suggesting an altered microvascular function as a contributing cause to the impaired secretory activity. Capacitance measurements of depolarization-induced exocytosis indicate a direct effect on the exocytotic machinery, in particular a dramatic reduction in readily releasable granules, as responsible for the insulin-secretory defect operating in Shb-/- islets. Shb-/- mice exhibited no alteration of islet volume or beta-cell area. In conclusion, loss of Shb impairs insulin secretion, alters islet microvascular morphology, and increases the basal blood glucose concentration. The impaired insulin secretory response is a plausible underlying cause of the metabolic impairment observed in this mutant mouse.
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| 18. |
- Åkerblom, Sophia, et al.
(författare)
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A network analysis of chronic pain rehabilitation program registry data: Structure, change, and responder analyses
- 2020
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Konferensbidrag (refereegranskat)abstract
- Background: Efforts to identify specific variables most related to outcomes in interdisciplinary pain rehabilitation are challenged by the complexity of chronic pain. Methods to manage this complexity are needed. In this study we apply network analysis to a large sample of people seeking interdisciplinary pain treatment. The purpose of the study was to determine the network structure entailed in the set of variables, examine change, and look at potential predictors of outcome, from a network perspective. Methods: Participants in this research (N = 2,421, age M = 43.8 years, % women = 82.2%) were all those consecutive cases providing pre- and post treatment data in the Swedish Quality Registry for Pain Rehabilitation (SQRP). Variables analyzed include pain intensity, pain interference, extent of pain, depression, anxiety, insomnia, and psychological variables from cognitive behavioral models of chronic pain. Network estimation, plotting, accuracy, and changes were call calculated in R. Results: We found Acceptance, Pain Interference, and Depression to be key, “central,” variables in the network of self-reported clinical variables. Interestingly, there were few changes in the network structure following treatment, particularly with respect to which variables appeared most central. On the other hand, Catastrophizing, Depression, Anxiety, and Pain Interference each became less central. The variables where changes were most strongly related to changes in the remainder of the network as a whole were Life Control, Acceptance, and Anxiety. Finally, no network differences were found between treatment responders and non-responders. Conclusions: Further application of a network approach to pain rehabilitation data is recommended. Future studies may improve upon the current results by selecting variables for analysis in a theoretically guided fashion and approaching the data ideographically, to detect unique individual differences in potential treatment processes.
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| 19. |
- Åkerblom, Sophia, et al.
(författare)
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A network analysis of clinical variables in chronic pain: a study from the Swedish quality registry for pain rehabilitation (SQRP)
- 2021
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Ingår i: Pain Medicine. - : Oxford University Press (OUP). - 1526-2375 .- 1526-4637. ; 22:7, s. 1591-1602
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Tidskriftsartikel (refereegranskat)abstract
- Background. Efforts to identify specific variables that impact most on outcomes from interdisciplinary pain rehabilitation are challenged by the complexity of chronic pain. Methods to manage this complexity are needed. The purpose of the study was to determine the network structure entailed in a set of self-reported variables, examine change, and look at potential predictors of outcome, from a network perspective. Methods. In this study we apply network analysis to a large sample of people seeking interdisciplinary pain treatment (N = 2,241). Variables analyzed include pain intensity, pain interference, extent of pain, depression, anxiety, insomnia, and psychological variables from cognitive behavioral models of chronic pain. Results. We found that Acceptance, Pain Interference, and Depression were key, “central,” variables in the pretreatment network. Interestingly, there were few changes in the overall network configuration following treatment, specifically with respect to which variables appear most central relative to each other. On the other hand, Catastrophizing, Depression, Anxiety, and Pain Interference each became less central over time. Changes in Life Control, Acceptance, and Anxiety were most strongly related to changes in the remainder of the network as a whole. Finally, no network differences were found between treatment responders and non-responders. Conclusions. This study highlights potential future targets for pain treatment. Further application of a network approach to interdisciplinary pain rehabilitation data is recommended. Going forward, it may be better to next do this in a more comprehensive theoretically guided fashion, and ideographically, to detect unique individual differences in potential treatment processes.
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| 20. |
- Åkerblom, Staffan, et al.
(författare)
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Formation and mobilization of methylmercury across natural and experimental sulfur deposition gradients
- 2020
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 263
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the influence of sulfate (SO42-) deposition and concentrations on the net formation and solubility of methylmercury (MeHg) in peat soils. We used data from a natural sulfate deposition gradient running 300 km across southern Sweden to test the hypothesis posed by results from an experimental field study in northern Sweden: that increased loading of SO42- both increases net MeHg formation and redistributes methylmercury (MeHg) from the peat soil to its porewater. Sulfur concentrations in peat soils correlated positively with MeHg concentrations in peat porewater, along the deposition gradient similar to the response to added SO42- in the experimental field study. The combined results from the experimental field study and deposition gradient accentuate the multiple, distinct and interacting roles of SO42- deposition in the formation and redistribution of MeHg in the environment.
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| 21. |
- Åkerblom, Staffan, et al.
(författare)
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Significant interaction effects from sulfate deposition and climate on sulfur concentrations constitute major controls on methylmercury production in peatlands
- 2013
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037 .- 1872-9533 .- 0046-564X. ; 102, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Transformation of inorganic mercury (Hg) to methyl mercury (MeHg) in peatlands is a key process in making boreal catchments a source of MeHg to freshwater ecosystems. Due to the importance of sulfur-reducing bacteria (SRB) for this process, past atmospheric deposition of sulfate (SO42−) may have increased net terrestrial Hg methylation. A long-term (14-year) factorial design field experiment was used to investigate the effect of enhanced SO42− deposition and raised temperature using a greenhouse (GH) treatment (air temperature∼+4 °C; soil temperature 20 cm below mire surface ∼+2 °C) on sulfur (S) turnover, net Hg methylation, MeHg and total Hg concentrations in a boreal mire in northern Sweden. Of the SO42−–S added during 14 years, 50% was retained in the plots without GH treatment while the combination of SO42− addition and GH treatment resulted in 15% S retention. The addition of SO42− (7-fold ambient SO42−-deposition) increased (p < 0.05) the net Hg methylation (200%) as well as the store of S (150%) and MeHg (120%) in the peat. A combination of enhanced SO42− deposition and GH treatment decreased both the net Hg methylation rate constant (0.018 ± 0.006 d−1) and MeHg content (1.2 ± 0.2 ng g−1 dry weight (dw)) relative to the sites with enhanced SO42− deposition without GH treatment (0.065 ± 0.013 d−1 and 3.7 ± 0.6 ng g−1 dw, respectively). The concentration of Hg in the peat declined (p < 0.05) in response to experimental addition of SO42−. Despite the decrease in Hg in response to SO42− deposition, these plots had the highest amounts of MeHg as well as the highest Hg methylation rate constants. This indicates that the concentration of S is more important than the concentration of Hg for the production of MeHg in this boreal landscape. These results also show that long-term chronic SO42− deposition at rates similar to those found in polluted areas of Europe and North America increase the capacity of wetlands to methylate Hg and store MeHg, which can ultimately be released to streams and lakes. This study also, for the first time, indicates that the enhancing effect of SO42− on the production of MeHg might be counteracted by increased temperature.
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