| 1. |
- Bränström, Robert, et al.
(författare)
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Electrical short-circuit in β-cells from a patient with non-insulinoma pancreatogenous hypoglycemic syndrome (NIPHS) : a case report
- 2010
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Ingår i: Journal of Medical Case Reports. - : Springer Science and Business Media LLC. - 1752-1947. ; 4:1, s. 315-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Non-insulinoma pancreatogenous hypoglycemic syndrome is a rare disorder among adults, and, to our knowledge, only about 40 cases have been reported in the literature. CASE PRESENTATION: The patient is a previously healthy 35-year-old Caucasian man. His symptoms began four years ago when he suddenly felt weakness in his legs and started sweating for unknown reasons. The symptoms worsened, and laboratory tests revealed hypoglycemia and hyperinsulinemia at the time of the symptoms. All diagnostics attempts using magnetic resonance imaging, computed tomography, and endoscopic ultrasound did not reveal any abnormalities. At this stage, surgical intervention was planned, and a distal 80% pancreatectomy was performed. The histopathologic and immunohistochemical investigations of the pancreas showed an increased number of islets of different sizes, more or less evenly distributed in the gland, but no insulinoma. Patch-clamp recordings from isolated pancreatic β-cells showed that, even at a low glucose concentration (3 mmol/L), the β-cell membrane was depolarized, and action potentials were seen. Surprisingly, in patch-clamp experiments, the addition of diazoxide had a marked effect on K-ATP channel activity and membrane potential, but no effect on insulin levels in vivo before surgery. CONCLUSION: This case report adds new information on the pathogenesis of non-insulinoma pancreatogenous hypoglycemic syndrome, as we performed an electrophysiologic characterization of isolated islet cells. We show, for the first time, that β-cells isolated from a non-insulinoma pancreatogenous hypoglycemic syndrome patient are constantly depolarized, even at low glucose levels, but display normal K-ATP channel physiology.
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| 2. |
- Juntti-Berggren, Lisa, et al.
(författare)
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Dihydroxyacetone-induced oscillations in cytoplasmic free Ca2+ and the ATP/ADP ratio in pancreatic beta-cells at substimulatory glucose.
- 2003
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 278:42, s. 40710-40716
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Tidskriftsartikel (refereegranskat)abstract
- Glucose stimulation of pancreatic beta-cells causes oscillatory influx of Ca2+, leading to pulsatile insulin secretion. We have proposed that this is due to oscillations of glycolysis and the ATP/ADP ratio, which modulate the activity of ATP-sensitive K+ channels. We show here that dihydroxyacetone, a secretagogue that feeds into glycolysis below the putative oscillator phosphofructokinase, could cause a single initial peak in cytoplasmic free Ca2+ ([Ca2+]i) but did not by itself cause repeated oscillations in [Ca2+]i in mouse pancreatic beta-cells. However, in the presence of a substimulatory concentration of glucose (4 mm), dihydroxyacetone induced [Ca2+]i oscillations. Furthermore, these oscillations correlated with oscillations in the ATP/ADP ratio, as seen previously with glucose stimulation. Insulin secretion in response to dihydroxyacetone was transient in the absence of glucose but was considerably enhanced and somewhat prolonged in the presence of a substimulatory concentration of glucose, in accordance with the enhanced [Ca2+]i response. These results are consistent with the hypothesized role of phosphofructokinase as the generator of the oscillations. Dihydroxyacetone may affect phosphofructokinase by raising the free concentration of fructose 1,6-bisphosphate to a critical level at which it activates the enzyme autocatalytically, thereby inducing the pulses of phosphofructokinase activity that cause the metabolic oscillations.
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| 3. |
- Avall, Karin, et al.
(författare)
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Apolipoprotein CIII links islet insulin resistance to beta-cell failure in diabetes
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:20, s. E2611-E2619
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and beta-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and beta-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of beta-cell cytoplasmic free Ca2+ concentration ([Ca2+](i)) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca2+](i) response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of beta-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.
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| 4. |
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| 5. |
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| 6. |
- Bergkvist, Bo, et al.
(författare)
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Pools and fluxes of carbon in three Norway spruce ecosystems along a climatic gradient in Sweden
- 2008
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 89:1, s. 7-25
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents an integrated analysis of organic carbon (C) pools in soils and vegetation, within-ecosystem fluxes and net ecosystem exchange (NEE) in three 40-year old Norway spruce stands along a north-south climatic gradient in Sweden, measured 2001-2004. A process-orientated ecosystem model (CoupModel), previously parameterised on a regional dataset, was used for the analysis. Pools of soil organic carbon (SOC) and tree growth rates were highest at the southernmost site (1.6 and 2.0-fold, respectively). Tree litter production (litterfall and root litter) was also highest in the south, with about half coming from fine roots (< 1 mm) at all sites. However, when the litter input from the forest floor vegetation was included, the difference in total litter input rate between the sites almost disappeared (190-233 g C m(-2) year(-1)). We propose that a higher N deposition and N availability in the south result in a slower turnover of soil organic matter than in the north. This effect seems to overshadow the effect of temperature. At the southern site, 19% of the total litter input to the O horizon was leached to the mineral soil as dissolved organic carbon, while at the two northern sites the corresponding figure was approx. 9%. The CoupModel accurately described general C cycling behaviour in these ecosystems, reproducing the differences between north and south. The simulated changes in SOC pools during the measurement period were small, ranging from -8 g C m(-2) year(-1) in the north to +9 g C m(-2) year(-1) in the south. In contrast, NEE and tree growth measurements at the northernmost site suggest that the soil lost about 90 g C m(-2) year(-1).
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| 7. |
- Eliasson, Lena, et al.
(författare)
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PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells
- 1996
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 271:5250, s. 813-815
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Tidskriftsartikel (refereegranskat)abstract
- Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which suggests that it contributes to their hypoglycemic action in diabetics.
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| 8. |
- Forsman, Anders, et al.
(författare)
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Pike Esox lucius as an emerging model organism for studies in ecology and evolutionary biology: a review.
- 2015
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Ingår i: Journal of Fish Biology. - : Wiley. - 0022-1112 .- 1095-8649. ; 87:2, s. 472-479
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Forskningsöversikt (refereegranskat)abstract
- The pikeEsox luciusis a large, long-lived, iteroparous, top- predator fish species with a circumpolardistribution that occupies a broad range of aquatic environments. This study reports on a literaturesearch and demonstrates that the publication rate ofE. luciusresearch increases both in absolute termsand relative to total scientific output, and that the focus of investigation has changed over time frombeing dominated by studies on physiology and disease to being gradually replaced by studies on ecol-ogy and evolution.Esox luciuscan be exploited as a model in future research for identifying causes andconsequences of phenotypic and genetic variation at the levels of individuals, populations and speciesas well as for investigating community processes.
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| 9. |
- Henriksnäs, Johanna, et al.
(författare)
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Markedly Decreased Blood Perfusion of Pancreatic Islets Transplanted Intraportally Into the Liver : Disruption of Islet Integrity Necessary for Islet Revascularization
- 2012
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:3, s. 665-673
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Tidskriftsartikel (refereegranskat)abstract
- Experimental studies indicate low revascularization of intraportally transplanted islets. This study aimed to quantify, for the first time, the blood perfusion of intrahepatically transplanted islets and elucidate necessary factors for proper islet graft revascularization at this site. Yellow chameleon protein 3.0 islets expressing fluorescent protein in all cells were transplanted. Graft blood perfusion was determined by microspheres. The vascular density and relative contribution of donor blood vessels in revascularization was evaluated using islets expressing green fluorescent protein under the Tie-2 promoter. Blood perfusion of intrahepatic islets was as a mean only 5% of that of native islets at 1-month posttransplantation. However, there was a marked heterogeneity where blood perfusion was less decreased hi islets transplanted without prior culture and in many cases restored in islets with disrupted integrity. Analysis of vascular density showed that distorted islets were well revascularized, whereas islets still intact at 1-month posttransplantation were almost avascular. Few donor endothelial cells were observed in the new islet vasculature. The very low blood perfusion of intraportally transplanted islets is likely to predispose for ischemia and hamper islet function. Since donor endothelial cells do not expand posttransplantation, disruption of islet integrity is necessary for revascularization to occur by recipient blood vessels.
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| 10. |
- Holmberg, Rebecka, et al.
(författare)
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Antiviral treatments reduce severity of diabetes in Ljungan virus-infected CD-1 mice and delay onset in diabetes-prone BB rats
- 2009
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Ingår i: Microbiology and immunology. - : Wiley. - 0385-5600 .- 1348-0421. ; 53:10, s. 567-572
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Tidskriftsartikel (refereegranskat)abstract
- The effects of LV in two different species, CD-1 mice, without a genetic disposition for diabetes, and BB rats prone to T1D were examined. Male CD-1 mice that had been exposed to LV in utero developed a type 2-like diabetes with increased blood glucose, insulin levels and epididymal fat at the age of 10-15 weeks. Combination therapy including LV-antiserum and an antiviral drug, Pleconaril, significantly reduced the levels of blood glucose and insulin and the amount of abdominal fat. In BB rats, LV has been found in both prediabetic- and diabetic diabetes-prone rats, as well as in diabetes-resistant rats. To evaluate whether the presence of LV has any influence on the onset of T1D, prediabetic BB rats were treated with an antiserum against LV or a combination of the antiviral drugs Pleconaril and Ribavirin. In the group treated with antiviral drugs, the onset was significantly delayed. These results indicate that the presence of LV can be involved in the pathogenesis of diabetes in these animal models.
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| 11. |
- Holmberg, Rebecka, et al.
(författare)
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Lowering apolipoprotein CIII delays onset of type 1 diabetes
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:26, s. 10685-10689
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Tidskriftsartikel (refereegranskat)abstract
- Serum levels of apolipoprotein CIII (apoCIII) are increased in type 1 diabetic patients, and when β cells are exposed to these diabetic sera, apoptosis occurs, an effect abolished by an antibody against apoCIII. We have investigated the BB rat, an animal model that develops a human-like type 1 diabetes, and found that apoCIII was also increased in sera from prediabetic rats. This increase in apoCIII promoted β-cell death. The endogenous levels of apoCIII were reduced by treating prediabetic animals with an antisense against this apolipoprotein, resulting in a significantly delayed onset of diabetes. ApoCIII thus serves as a diabetogenic factor, and intervention with this apolipoprotein in the prediabetic state can arrest disease progression. These findings suggest apoCIII as a target for the treatment of type 1 diabetes.
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| 12. |
- Lau, Joey, et al.
(författare)
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Beneficial role of pancreatic microenvironment for angiogenesis in transplanted pancreatic islets
- 2009
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 18:1, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic islets implanted heterotopically (i.e., into the kidney, spleen, or liver) become poorly revascularized following transplantation. We hypothesized that islets implanted into the pancreas Would become better revascularized. Islets isolated from transgenic mice expressing enhanced yellow fluorescent protein (EYFP) in all somatic cells were Cultured before they were implanted into the pancreas or beneath the renal capsule of athymic mice. Vascular density was evaluated in histological sections 1 month posttransplantation. EYFP was used as reporter for the transgene to identify the transplanted islets. Islet endothelial cells were visualized by staining with the lectin Bandeiraea simplicifolia (BS-1). Capillary numbers in intrapancreatically implanted islets were only slightly lower than those counted in endogenous islets, whereas islets implanted beneath the renal capsule had a markedly lower vascular density. In order to determine if this high graft vascular density at the intrapancreatic site reflected expansion of remnant donor endothelial cells or increased ingrowth of blood vessels from the host. also islets from Tie2-green fluorescent protein (GFP) mice (i.e., islets with fluorescent endothelial cells) were transplanted into the pancreas or beneath the renal capsule of athymic mice. These islet grafts revealed that the new vascular structures formed in the islet grafts contained very few GFP-positive cells, and thus mainly were of recipient origin. The reason(s) for the much better ingrowth of blood vessels at the intrapancreatic site merits further studies, because this may help us form strategies to overcome the barrier for ingrowth of host vessels also into islets in heterotopic implantation sites.
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| 13. |
- Lau, Joey, et al.
(författare)
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Implantation site-dependent dysfunction of transplanted pancreatic islets
- 2007
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 56:6, s. 1544-1550
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Clinical islet transplantations are performed through infusion of islets via the portal vein into the liver. This study aimed at characterizing the influence of the implantation microenvironment on islet graft metabolism and function. RESEARCH DESIGN AND METHODS—Islets were transplanted into their normal environment, i.e., the pancreas, or intraportally into the liver of mice. One month posttransplantation, the transplanted islets were retrieved and investigated for changes in function and gene expression. RESULTS—Insulin content, glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate were markedly decreased in islets retrieved from the liver, both when compared with islets transplanted into the pancreas and endogenous islets. Islets transplanted into the pancreas showed normal insulin content, (pro)insulin biosynthesis, and glucose oxidation rate but increased basal insulin secretion and impaired glucose stimulation index. Gene expression data for retrieved islets showed downregulation of pancreatic and duodenal homeobox gene-1, GLUT-2, glucokinase, mitochondrial glycerol-phosphate dehydrogenase, and pyruvate carboxylase, preferentially in intraportally transplanted islets. CONCLUSIONS—Islets transplanted into their normal microenvironment, i.e., the pancreas, display gene expression changes when compared with endogenous islets but only moderate changes in metabolic functions. In contrast, site-specific properties of the liver markedly impaired the metabolic functions of intraportally transplanted islets.
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| 14. |
- Niklasson, Bo, et al.
(författare)
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Diabetes Prevention Through Antiviral Treatment in Biobreeding Rats
- 2016
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Ingår i: Viral immunology. - : Mary Ann Liebert Inc. - 0882-8245 .- 1557-8976. ; 29:8, s. 452-458
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Tidskriftsartikel (refereegranskat)abstract
- A picornavirus (Ljungan virus) has been associated with diabetes in its wild rodent reservoir and in diabetesprone biobreeding (DP-BB) rats. We attempted to alter the development of diabetes in DP-BB rats using two anti-picornavirus compounds (pleconaril and APO-N039), singly or in combination. Antiviral therapy was initiated 2 weeks before expected onset of diabetes. Pleconaril or APO-N039 alone did not affect the debut of diabetes. However, animals receiving a combination of both compounds were protected for at least the entire period of treatment (4 weeks after expected time of diabetes onset). Immunohistochemistry demonstrated that the presence and distribution of virus antigen in the pancreatic islets coincided with the clinical status of the animal. Data indicate that a treatable picornavirus can be involved in the cellular assault resulting in diabetes and in these cases the disease mechanism appears to involve a virus present in the pancreatic beta cell mass itself.
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| 15. |
- Nordahl, Oscar, et al.
(författare)
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Sun-basking fish benefit from body temperatures that are higher than ambient water
- 2018
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - London : The Royal Society. - 0962-8452 .- 1471-2954. ; 285:1879
-
Tidskriftsartikel (refereegranskat)abstract
- In terrestrial environments, cold-blooded animals can attain higher bodytemperatures by sun basking, and thereby potentially benefit from broaderniches, improved performance and higher fitness. The higher heat capacityand thermal conductivity of water compared with air have been universallyassumed to render heat gain from sun basking impossible for aquaticectotherms, such that their opportunities to behaviourally regulate body temperatureare largely limited to choosing warmer or colder habitats. Here wechallenge this paradigm. Using physical modelswe first showthat submergedobjects exposed to natural sunlight attain temperatures in excess of ambientwater. We next demonstrate that free-ranging carp (Cyprinus carpio) canincrease their body temperature during aquatic sun basking close to thesurface. The temperature excess gained by basking was larger in dark thanin pale individuals, increased with behavioural boldness, and was associatedwith faster growth. Overall, our results establish aquatic sun basking as a novelecologically significant mechanism for thermoregulation in fish. The discoveryof this previously overlooked process has practical implications for aquaculture,offers alternative explanations for behavioural and phenotypicadaptations, will spur future research in fish ecology, and calls for modificationsof models concerning climate change impacts on biodiversity inmarine and freshwater environments.
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| 16. |
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| 17. |
- Pålsgård, Eva, et al.
(författare)
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Effects of K+-induced depolarization and purinergic receptor activation on elemental content in insulin-producing RINm5F-cells
- 1995
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Ingår i: Cell Biology International. - : Wiley. - 1065-6995 .- 1095-8355. ; 19:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- X-ray microanalysis was used to detect elemental changes in the insulin-producing tumor cell-lineRINm5F. To improve discrimination between mobile ions and ions bound to macromolecules a new approach was employed, consisting of multivariate statistical analysis of correlations between the concentrations of Na, Mg, P, S, CI, K, and Ca. RINm5F cells, cultured an Formvar-coated titanium grids, were stimulated with high K+ or ATP, that are both known to stimulate insulin release. The buffers used contained Ca2+ or one of the Ca2+-analogues Sr2+ and Ba2+, to represent Ca2+ uptake inresponse to stimulation. After stimulation the cells were shock-frozen and freeze-dried overnight. Incubation for 10-20 seconds in a Ca2+-containing buffer did not significantly affect elementalcomposition, whereas cellular Mg, P and K decreased in a Sr2+-containing buffer. Depolarization with high K+ concentration caused an increase in the cellular Na content, both in Ca2+- and Sr2+-containing buffers, but not in the buffer where Ca2+ had been replaced by Ba2+. X-ray microanalysis is useful for detection of elemental changes subsequent to stimulation of cultured cells. Moreover, multivariate statistical analysis strengthens the idea that stimulation of RINm5F cells causes redistribution of ions possibly due to changes in the state of binding of some elements to cellular proteins.
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| 18. |
- Pålsgård, Eva, et al.
(författare)
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Proton-induced and electron-induced X-ray microanalysis of insulin-secreting cells
- 1994
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Ingår i: Scanning Microscopy Suppl.. ; 8, s. 325-333
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Tidskriftsartikel (refereegranskat)abstract
- Elemental redistribution induced by insulin secretion, was investigated by electron and proton probe X-ray microanalysis. In particular, ion fluxes following immediately upon stimulation were studied. As the sensitivity of the electron probe was insufficient, the proton microprobe was employed. In order to see whether the cell is asymmetric with respect to Ca2+ influx, the cells were stimulated in the presence of Sr2+ (as a Ca2+ analog). Insulin-secreting cells (RINm5F cells and isolated mouse beta-cells) were cultured on grids and shock-frozen at 2-30 seconds after stimulation. In a large number of cells, the major elements and and large fluxes were analyzed by the electron microprobe. In the proton microprobe, selected cells were analyzed and elemental maps were compared with electron micrographs of the same cells. The proton microprobe, but not the electron microprobe, could detect an influx of Sr in response to K+-stimulation for 2 seconds, in RINm5F cells. No polarization of Sr2+ uptake in RINm5F-cells could be detected, and the beta-cells did not respond to high K+ by uptake of Sr. Momentary stimulation of beta-cells also resulted in a significant increase in Na, detected by the electron probe. Spreading of the beta-cells on the substrate appears to influence the subcellular elemental distribution. Thus, the proton probe has potential to detect small changes in elements such as those occurring after short-time stimulation.
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| 19. |
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| 20. |
- Solé-Domènech, Santiago, et al.
(författare)
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Localization of cholesterol, amyloid and glia in Alzheimer's disease transgenic mouse brain tissue using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and immunofluorescence imaging
- 2013
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 125:1, s. 145-157
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Tidskriftsartikel (refereegranskat)abstract
- The spatial distributions of lipids, amyloid-beta deposits, markers of neurons and glial cells were imaged, at submicrometer lateral resolution, in brain structures of a mouse model of Alzheimer's disease using a new methodology that combines time-of-flight secondary ion mass spectrometry (ToF-SIMS) and confocal fluorescence microscopy. The technology, which enabled us to simultaneously image the lipid and glial cell distributions in Tg2576 mouse brain structures, revealed micrometer-sized cholesterol accumulations in hippocampal regions undergoing amyloid-beta deposition. Such cholesterol granules were either associated with individual amyloid deposits or spread over entire regions undergoing amyloidogenesis. Subsequent immunohistochemical analysis of the same brain regions showed increased microglial and astrocytic immunoreactivity associated with the amyloid deposits, as expected from previous studies, but did not reveal any particular astrocytic or microglial feature correlated with cholesterol granulation. However, dystrophic neurites as well as presynaptic vesicles presented a distribution similar to that of cholesterol granules in regions undergoing amyloid-beta accumulation, thus indicating that these neuronal endpoints may retain cholesterol in areas with lesions. In conclusion, the present study provides evidence for an altered cholesterol distribution near amyloid deposits that would have been missed by several other lipid analysis methods, and opens for the possibility to study in detail the putative liaison between lipid environment and protein structure and function in Alzheimer's disease.
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| 21. |
- Størling, Joachim, et al.
(författare)
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Apolipoprotein CIII reduces proinflammatory cytokine-induced apoptosis in rat pancreatic islets via the Akt prosurvival pathway
- 2011
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 152:8, s. 3040-3048
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein CIII (ApoCIII) is mainly synthesized in the liver and is important for triglyceride metabolism. The plasma concentration of ApoCIII is elevated in patients with type 1 diabetes (T1D), and in vitro ApoCIII causes apoptosis in pancreatic β-cells in the absence of inflammatory stress. Here, we investigated the effects of ApoCIII on function, signaling, and viability in intact rat pancreatic islets exposed to proinflammatory cytokines to model the intraislet inflammatory milieu in T1D. In contrast to earlier observations in mouse β-cells, exposure of rat islets to ApoCIII alone (50 μg/ml) did not cause apoptosis. In the presence of the islet-cytotoxic cytokines IL-1β + interferon-γ, ApoCIII reduced cytokine-mediated islet cell death and impairment of β-cell function. ApoCIII had no effects on mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, and ERK) and had no impact on IL-1β-induced c-Jun N-terminal kinase activation. However, ApoCIII augmented cytokine-mediated nitric oxide (NO) production and inducible NO synthase expression. Further, ApoCIII caused degradation of the nuclear factor κB-inhibitor inhibitor of κB and stimulated Ser473-phosphorylation of the survival serine-threonine kinase Akt. Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces rat pancreatic islet cell apoptosis via Akt.
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| 22. |
- Valladolid-Acebes, Ismael, et al.
(författare)
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Lowering apolipoprotein CIII protects against high-fat diet-induced metabolic derangements
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of apolipoprotein CIII (apoCIII), a key regulator of lipid metabolism, result in obesity-related metabolic derangements. We investigated mechanistically whether lowering or preventing high-fat diet (HFD)-induced increase in apoCIII protects against the detrimental metabolic consequences. Mice, first fed HFD for 10 weeks and thereafter also given an antisense (ASO) to lower apoCIII, already showed reduced levels of apoCIII and metabolic improvements after 4 weeks, despite maintained obesity. Prolonged ASO treatment reversed the metabolic phenotype due to increased lipase activity and receptor-mediated hepatic uptake of lipids. Fatty acids were transferred to the ketogenic pathway, and ketones were used in brown adipose tissue (BAT). This resulted in no fat accumulation and preserved morphology and function of liver and BAT. If ASO treatment started simultaneously with the HFD, mice remained lean and metabolically healthy. Thus, lowering apoCIII protects against and reverses the HFD-induced metabolic phenotype by promoting physiological insulin sensitivity.
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| 23. |
- von Seth, Erik, et al.
(författare)
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Distribution of intraportally implanted microspheres and fluorescent islets in mice
- 2007
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 16:6, s. 621-627
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate the distribution of intraportally transplanted islets in mice. We initially administered 2000 polystyrene microspheres with a diameter of 50 microm intraportally into normoglycemic C57BL/6 mice. In separate experiments other mice were injected similarly with 300 microspheres each with a diameter of 100 or 200 microm. One week later the animals were killed, and the lungs and livers were removed and divided into lobes. The number of microspheres in each individual liver lobe and in the lungs was counted using a stereomicroscope. In other experiments, athymic C57BL/6 mice were similarly implanted with 250 islets isolated from transgenic mice expressing the enhanced yellow fluorescent protein in the islet cells. The distribution of microspheres and islets was independent of size, and fairly homogenous within the liver, with the exception of the caudate lobe, which contained fewer microspheres and islets, respectively. Approximately one third of all microspheres and islets were present as aggregates. Eighty-five to 90% of the implanted microspheres were identified in the liver sections, whereas 60-65% of the implanted islets were recovered. Aggregates or single fluorescent cells were observed in the liver of islet-implanted mice. We conclude that islets and microspheres implanted into the liver distribute fairly homogenously and quite a few of them exist as aggregates or, with respect to islets, as fragments.
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| 24. |
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| 25. |
- Addinsall, Alex B., et al.
(författare)
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Ruxolitinib : A new hope for ventilator-induced diaphragm dysfunction
- 2024
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 240:5
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Mechanical ventilation (MV) results in diminished diaphragm size and strength, termed ventilator-induced diaphragm dysfunction (VIDD). VID increases dependence, prolongs weaning, and increases discharge mortality rates. The Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is implicated in VIDD, upregulated following MV. JAK/STAT inhibition alleviates chronic muscle wasting conditions. This study aimed to explore the therapeutic potential of Ruxolitinib, an FDA approved JAK1/2 inhibitor (JI) for the treatment of VIDD. Methods: Rats were subjected to 5 days controlled MV (CMV) with and without daily Ruxolitinib gavage. Muscle fiber size and function were assessed. RNAseq, mitochondrial morphology, respirometry, and mass spectrometry were determined. Results: CMV significantly reduced diaphragm size and specific force by 45% (p < 0.01), associated with a two-fold P-STAT3 upregulation (p < 0.001). CMV disrupted mitochondrial content and reduced the oxygen consumption rate (p < 0.01). Expression of the motor protein myosin was unaffected, however CMV alters myosin function via post-translational modifications (PTMs). Daily administration of JI increased animal survival (40% vs. 87%; p < 0.05), restricted P-STAT3 (p < 0.001), and preserved diaphragm size and specific force. JI was associated with preserved mitochondrial content and respiratory function (p < 0.01), and the reversal or augmentation of myosin deamidation PTMs of the rod and head region. Conclusion: JI preserved diaphragm function, leading to increased survival in an experimental model of VIDD. Functional enhancement was associated with maintenance of mitochondrial content and respiration and the reversal of ventilator-induced PTMs of myosin. These results demonstrate the potential of repurposing Ruxolitinib for treatment of VIDD.
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| 26. |
- Ali, Yusuf, et al.
(författare)
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The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice
- 2016
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:5, s. 1007-1011
-
Tidskriftsartikel (refereegranskat)abstract
- In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non-invasively imaged the pancreatic bud as it develops at single beta cell resolution across time. The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo.
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| 27. |
- Amir, Omar A., 1963-
(författare)
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Biology, ecology and anthropogenic threats of Indo-Pacific bottlenose dolphins in east Africa
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the biology, ecology and anthropogenic threats of Indo-Pacific bottlenose dolphins (Tursiops aduncus) off Zanzibar, Tanzania, based on research conducted and samples collected between 2000 and 2008. Distribution and occurrence are described based on incidental catches (bycatch) in gillnet fisheries. Biology and ecology are examined by ageing and studying the reproductive biology and stomach contents of collected specimens. The composition of organohalogen compounds is determined in blubber samples, and assessment and mitigation of bycatch are conducted using observers onboard fishing vessels. Fisheries bycatch data showed that Indo-Pacific bottlenose dolphins occur year round in all areas around Zanzibar. Sexual maturity was attained between 7 and 8 years and body length 190-200 cm in females and at 16 years and body length 213 cm in males. The gestation period was estimated to be 12.3 months, with calving occurring throughout the year, peaking November-March and with an interval of 2.7 years. The estimated pregnancy rate was between 0.10 and 0.58 depending on methods used. Stomach contents revealed a relatively large number of prey species, but that only a few small- and medium-sized neritic fish and cephalopods contribute substantially to the diet. Estimates of total annual bycatch were >9% which is not considered sustainable. An experiment showed that pingers can be a short term mitigation measure to reduce bycatch of dolphins in both drift- and bottom set gillnets. Methoxylated polybrominated diphenyl ethers (Meo-BDEs) were found at higher concentrations than anthropogenic organic pesticides (OCPs), with only traces of polychlorinated biphenyls (PCBs) detected. This study reveals the magnitude and apparent susceptibility of Indo-Pacific bottlenose dolphins off Zanzibar to anthropogenic threats, especially fisheries bycatch, and it is clear that immediate conservation and management measures are needed to reduce bycatch.
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| 28. |
- Amir, Omar A., et al.
(författare)
-
Estimates of bycatch and field experiment using pingers to reduce bycatch of dolphins in drift- and bottom set gillnets in Menai Bay, Zanzibar, Tanzania
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In order to estimate the total bycatch in gillnet fisheries and to assess the impact on dolphin populations in the Menai Bay Conservation Area, a survey using independent observers aboard the fishing vessels was conducted in 2003/2004. The observer programme covered 23.6% and 24.5% of the drift- and bottom set gillnets effort, respectively. The estimated total bycatch was 13 Indo-Pacific bottlenose dolphins in drift gillnets and 4 humpback dolphins in bottom set gillnets representing 9.6% and 6.3%, respectively of the estimated 136 Indo-Pacific bottlenose and 63 humpback dolphins resident in the area in 2002. These bycatch levels were not considered sustainable. In 2007/2008 a second observer programme was conducted in the same area to investigate the effectiveness of acoustic alarms (pingers) in reducing the bycatch of dolphins in the drift- and bottom set gillnets. The observed effort in the drift gillnets was 257 sets without pingers and 251 sets with pingers representing 21% and 20% of the total recorded effort, respectively. Six dolphins were bycaught during the pinger experiment in the drift gillnets (1 Indo-Pacific bottlenose dolphin in sets with pingers and 4 Indo-Pacific bottlenose dolphins and 1 spinner dolphin in the sets without pingers). In the bottom set gillnet fishery, the observed fishing effort was 236 sets without pingers and 224 sets with pingers, representing 28% and 27% of the total recorded effort, respectively. In the bottom set gillnets, one humpback dolphin was bycaught in the sets without pingers and no dolphin was bycaught in the sets with pingers. Pingers reduced the bycatch of dolphins in both drift- and bottom set gillnets, however the reduction was only significant in the drift gillnets. Estimates of the total bycatch in the sets without pingers in 2007/2008 fishing season were 16 Indo-Pacific bottlenose dolphins in drift gillnets and 3 humpback dolphins in the bottom set gillnet fishery, representing 11.8% and 4.8% of estimated population size for respective species in the area in 2002. Given the documented unsustainable removal levels in the drift- and bottom set gillnets, immediate management actions are needed to reduce dolphin bycatch in these fisheries.
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| 29. |
- Amir, Omar A., et al.
(författare)
-
Feeding ecology of the Indo-Pacific bottlenose dolphin (Tursiops aduncus) incidentally caught in the gillnet fisheriesoff Zanzibar, Tanzania
- 2005
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Ingår i: Estuarine, Coastal and Shelf Science. - : Elsevier BV. - 0272-7714 .- 1096-0015. ; 63:3, s. 429-437
-
Tidskriftsartikel (refereegranskat)abstract
- The stomach contents of 26 Indo-Pacific bottlenose dolphins (Tursiops aduncus) incidentally caught in gillnet fisheries aroundUnguja Island (Zanzibar) between February 2000 and August 2002 were examined. The relative importance of each prey species wasassessed through indices of relative importance. In total, 1403 prey items comprising 50 species of bony fish and three species ofsquid were identified from food remains. Five species of fish, Uroconger lepturus, Synaphobranchus kaupii, Apogon apogonides,Lethrinus crocineus, Lutjanus fulvus, and three species of squid, Sepioteuthis lessoniana, Sepia latimanus and Loligo duvauceli, werethe most important prey species. Based on an index that included frequency of occurrence, percentage by number and by weight,Uroconger lepturus proved to be the most important prey species of mature dolphins whereas Apogon apogonides was the preferredprey of immature dolphins. These results indicate that Indo-Pacific bottlenose dolphins off the coast of Zanzibar forage ona relatively large number of prey species, but that only a few small- and medium-sized neritic fish and cephalopods contributesubstantially to the diet. Further, the ecology and behavior of the preferred fish prey species indicate that the dolphins forage overreef or soft bottom substrata and near the shore.
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| 30. |
- Amir, Omar A., et al.
(författare)
-
Growth and reproduction of Indo-Pacific bottlenose dolphins (Tursiops aduncus) incidentally caught in gillnets off Zanzibar, Tanzania
-
Tidskriftsartikel (refereegranskat)abstract
- Life history parameters of Indo-Pacific bottlenose dolphin (Tursiops aduncus) were examined in 69 specimens incidentally caught in gillnet fisheries off Zanzibar, Tanzania between 2000 and 2008. Calves were born at a body length of 103 cm and a weight of 12-15 kg. Sexual maturity in females was reached at 7-8 years and body length 190-200 cm. Sexual maturity in males was attained at 16 years and a body length of 213 cm. Calving occurred throughout the year with a peak November-March, after a gestation period of 12.3 months. The estimated pregnancy rate was 0.10 based on the proportion pregnant mature females in the sample and 0.58 based on the occurrence of Corpora Lutea in the ovaries. The average calving interval was calculated to 2.7 years. The results are important for assessment of fisheries bycatch mortality and conservation and management of Indo-Pacific bottlenose dolphins in western Indian Ocean
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| 31. |
- Amir, Omar A., et al.
(författare)
-
The occurrence and distribution of dolphins in Zanzibar, Tanzania, with comments on the differences between two species of Tursiops
- 2005
-
Ingår i: Western Indian Ocean Journal of Marine Science. - 0856-860X .- 2683-6416. ; 4:1, s. 85-93
-
Tidskriftsartikel (refereegranskat)abstract
- Incidental catches (bycatch) in gillnet fisheries off Zanzibar (Unguja Island), as asource of mortality among several species of dolphins, were reported in a questionnaire surveyconducted in 1999. As a follow-up to that survey, from January 2000 to August 2003, wemonitored the incidental catches of dolphins collected from 12 fish landing sites. Six species ofdolphins were recorded from 143 specimens retrieved from bycatches in drift- and bottom setgillnets. Of these, 68 (48%) were Indo-Pacific bottlenose dolphins (Tursiops aduncus), 44 (31%) spinner dolphins (Stenella longirostris), 12 (8%) Risso’s dolphins (Grampus griseus), 11 (8%) Indo-Pacific humpback dolphins (Sousa chinensis), 6 (4%) Pan-tropical spotted dolphins(Stenella attenuata) and 2 (1%) common bottlenose dolphins (Tursiops truncatus). Most of thebycatches (71%) were in nets set off the north coast of Unguja Island. In this paper, bycatchrecords are examined to describe the occurrence and distribution of dolphin species in UngujaIsland coastal waters. The relatively large numbers of bycatch dolphins recorded indicate thatbycatch may be a potential threat to local populations that need to be addressed in futureconservation and management efforts in the region.
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| 32. |
- Amoignon, Olivier, 1969-
(författare)
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Numerical Methods for Aerodynamic Shape Optimization
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gradient-based aerodynamic shape optimization, based on Computational Fluid Dynamics analysis of the flow, is a method that can automatically improve designs of aircraft components. The prospect is to reduce a cost function that reflects aerodynamic performances.When the shape is described by a large number of parameters, the calculation of one gradient of the cost function is only feasible by recourse to techniques that are derived from the theory of optimal control. In order to obtain the best computational efficiency, the so called adjoint method is applied here on the complete mapping, from the parameters of design to the values of the cost function. The mapping considered here includes the Euler equations for compressible flow discretized on unstructured meshes by a median-dual finite-volume scheme, the primal-to-dual mesh transformation, the mesh deformation, and the parameterization. The results of the present research concern the detailed derivations of expressions, equations, and algorithms that are necessary to calculate the gradient of the cost function. The discrete adjoint of the Euler equations and the exact dual-to-primal transformation of the gradient have been implemented for 2D and 3D applications in the code Edge, a program of Computational Fluid Dynamics used by Swedish industries.Moreover, techniques are proposed here in the aim to further reduce the computational cost of aerodynamic shape optimization. For instance, an interpolation scheme is derived based on Radial Basis Functions that can execute the deformation of unstructured meshes faster than methods based on an elliptic equation.In order to improve the accuracy of the shape, obtained by numerical optimization, a moving mesh adaptation scheme is realized based on a variable diffusivity equation of Winslow type. This adaptation has been successfully applied on a simple case of shape optimization involving a supersonic flow. An interpolation technique has been derived based on a mollifier in order to improve the convergence of the coupled mesh-flow equations entering the adaptive scheme.The method of adjoint derived here has also been applied successfully when coupling the Euler equations with the boundary-layer and parabolized stability equations, with the aim to delay the laminar-to-turbulent transition of the flow. The delay of transition is an efficient way to reduce the drag due to viscosity at high Reynolds numbers.
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| 33. |
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| 34. |
- Andersson, Erika, et al.
(författare)
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AhR agonist and genotoxicant bioavailability in a PAH-contaminated soil undergoing biological treatment
- 2009
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Ingår i: Environmental Science and Pollution Research. - : Springer Berlin/Heidelberg. - 0944-1344 .- 1614-7499. ; 16:5, s. 521-530
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Tidskriftsartikel (refereegranskat)abstract
- Degradation of the 16 US EPA priority PAHs in soil subjected to bioremediation is often achieved. However, the PAH loss is not always followed by a reduction in soil toxicity. For instance, bioanalytical testing of such soil using the chemical-activated luciferase gene expression (CALUX) assay, measuring the combined effect of all Ah receptor (AhR) activating compounds, occasionally indicates that the loss of PAHs does not correlate with the loss of Ah receptor-active compounds in the soil. In addition, standard PAH analysis does not address the issue of total toxicant bioavailability in bioremediated soil.To address these questions, we have used the CALUX AhR agonist bioassay and the Comet genotoxicity bioassay with RTL-W1 cells to evaluate the toxic potential of different extracts from a PAH-contaminated soil undergoing large-scale bioremediation. The extracts were also chemically analyzed for PAH16 and PCDD/PCDF. Soil sampled on five occasions between day 0 and day 274 of biological treatment was shaken with n-butanol with vortex mixing at room temperature to determine the bioavailable fraction of contaminants. To establish total concentrations, parts of the same samples were extracted using an accelerated solvent extractor (ASE) with toluene at 100A degrees C. The extracts were tested as inducers of AhR-dependent luciferase activity in the CALUX assay and for DNA breakage potential in the Comet bioassay.The chemical analysis of the toluene extracts indicated slow degradation rates and the CALUX assay indicated high levels of AhR agonists in the same extracts. Compared to day 0, the bioavailable fractions showed no decrease in AhR agonist activity during the treatment but rather an up-going trend, which was supported by increasing levels of PAHs and an increased effect in the Comet bioassay after 274 days. The bio-TEQs calculated using the CALUX assay were higher than the TEQs calculated from chemical analysis in both extracts, indicating that there are additional toxic PAHs in both extracts that are not included in the chemically derived TEQ.The response in the CALUX and the Comet bioassays as well as the chemical analysis indicate that the soil might be more toxic to organisms living in soil after 274 days of treatment than in the untreated soil, due to the release of previously sorbed PAHs and possibly also metabolic formation of novel toxicants.Our results put focus on the issue of slow degradation rates and bioavailability of PAHs during large-scale bioremediation treatments. The release of sorbed PAHs at the investigated PAH-contaminated site seemed to be faster than the degradation rate, which demonstrates the importance of considering the bioavailable fraction of contaminants during a bioremediation process.It has to be ensured that soft remediation methods like biodegradation or the natural remediation approach do not result in the mobilization of toxic compounds including more mobile degradation products. For PAH-contaminated sites this cannot be assured merely by monitoring the 16 target PAHs. The combined use of a battery of biotests for different types of PAH effects such as the CALUX and the Comet assay together with bioavailability extraction methods may be a useful screening tool of bioremediation processes of PAH-contaminated soil and contribute to a more accurate risk assessment. If the bioremediation causes a release of bound PAHs that are left undegraded in an easily extracted fraction, the soil may be more toxic to organisms living in the soil as a result of the treatment. A prolonged treatment time may be one way to reduce the risk of remaining mobile PAHs. In critical cases, the remediation concept might have to be changed to ex situ remediation methods.
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| 35. |
- Andersson, Peter, et al.
(författare)
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Active Matrix Displays Based on All-Organic Electrochemical Smart Pixels Printed on Paper
- 2002
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Ingår i: Advanced Materials. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 0935-9648 .- 1521-4095. ; 14:20, s. 1460-1464
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Tidskriftsartikel (refereegranskat)abstract
- An organic electronic paper display technology (see Figure and also inside front cover) is presented. The electrochromic display cell together with the addressing electrochemical transistor form simple smart pixels that are included in matrix displays, which are achieved on coated cellulose-based paper using printing techniques. The ion-electronic technology presented offers an opportunity to extend existing use of ordinary paper.
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| 36. |
- Andersson, Peter, 1976-
(författare)
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Electrochromic Polymer Devices: Active-Matrix Displays and Switchable Polarizers
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Major efforts have been spent during recent years in worldwide attempts to achieve an electronic paper technology; the common name for novel flexible displays utilizing substrates such as paper, plastics or thin metal sheets. Various kinds of technology are available that potentially will be used for an electronic paper, which differs from each other mainly with respect to the choice of active materials, substrates and manufacturing techniques. There are many applications for electronic paper technology, ranging from high-resolution displays used in electronic books to updateable large-area billboards. The latter suggests a novel electronic display function that could extend the utilization of cellulose-based paper, which is one of the most common materials ever produced by mankind, by using the paper as a thin and flexible carrier. The requirement for fast update speed in such large area applications would probably be a bit more relaxed compared to traditional display technologies, while low-power consumption and bi-stability are among the factors that should be further emphasized, together with the utilization of well-established printing techniques to enable low-cost manufacturing of the displays. The choice of active materials is therefore crucial in order to reach these objectives in reality and this paves the way for printable conjugated polymers with electrochromic properties. Chemical synthesis of these materials during the last decades has resulted in a vast variety of electrochromic polymers with custom-tailored functionality covering a broad range of optical absorption and electrical conductivities.This thesis review the studies done on the electrochemical switching of poly(3,4-ethylenedioxythiophene) (PEDOT). For this material both the electrical conductivity and the optical absorption is controlled by the oxidation state. Active matrix addressed displays that are printed on flexible substrates have been obtained by arranging electrochemical smart pixels, based on the combination of electrochemical transistors and electrochromic display cells, into cross-point matrices. The resulting polymer-based active-matrix displays are operated at low voltages and the same active material can be used in electrochemical transistors and conducting lines and in electrochromic display cells employing the electronic and the opto-electonic properties of the material, respectively. In addition to this, a switchable optical polarizer is briefly discussed. This is a device utilizing electrochromism of stretch-aligned polyaniline (PANI). The combination of two identical devices in a vertical architecture, orthogonally oriented with respect to each other, results in a filter in which the orientation of the polarized optical absorption is governed by the voltage polarity applied to the device.
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| 37. |
- Andersson, Peter, et al.
(författare)
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Organic Electrochemical Smart Pixels
- 2003
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Ingår i: Materials Research Society Symposium Proceedings. ; , s. D6.6-
-
Konferensbidrag (refereegranskat)
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| 38. |
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| 39. |
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| 40. |
- Arbring Sjöström, Theresia, et al.
(författare)
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A Decade of Iontronic Delivery Devices
- 2018
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Ingår i: Advanced Materials Technologies. - : Wiley. - 2365-709X. ; 3:5
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Forskningsöversikt (refereegranskat)abstract
- In contrast to electronic systems, biology rarely uses electrons as the signal to regulate functions, but rather ions and molecules of varying size. Due to the unique combination of both electronic and ionic/molecular conductivity in conjugated polymers and polyelectrolytes, these materials have emerged as an excellent tool for translating signals between these two realms, hence the field of organic bioelectronics. Since organic bioelectronics relies on the electron-mediated transport and compensation of ions (or the ion-mediated transport and compensation of electrons), a great deal of effort has been devoted to the development of so-called "iontronic" components to effect precise substance delivery/transport, that is, components where ions are the dominant charge carrier and where ionic-electronic coupling defines device functionality. This effort has resulted in a range of technologies including ionic resistors, diodes, transistors, and basic logic circuits for the precisely controlled transport and delivery of biologically active chemicals. This Research News article presents a brief overview of some of these "ion pumping" technologies, how they have evolved over the last decade, and a discussion of applications in vitro, in vivo, and in plantae.
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| 41. |
- Balan, Mirela, et al.
(författare)
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Noninvasive intravital high-resolution imaging of pancreatic neuroendocrine tumours
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 14636-14636
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical trials of cancer drugs in animal models are important for drug development. The Rip1Tag2 (RT2) transgenic mouse, a model of pancreatic neuroendocrine tumours (PNET), has provided immense knowledge about PNET biology, although tumour progression occurs in a location inaccessible for real-time monitoring. To overcome this hurdle we have developed a novel platform for intravital 3D imaging of RT2 tumours to facilitate real-time studies of cancer progression. Pre-oncogenic islets retrieved from RT2 mice were implanted into the anterior chamber of the eye (ACE) of host mice, where they engrafted on the iris, recruited blood vessels and showed continuous growth. Noninvasive confocal and two-photon laser-scanning microscopy through the transparent cornea facilitated high-resolution imaging of tumour growth and angiogenesis. RT2 tumours in the ACE expanded up to 8-fold in size and shared hallmarks with tumours developing in situ in the pancreas. Genetically encoded fluorescent reporters enabled high-resolution imaging of stromal cells and tumour cell migration. Sunitinib treatment impaired RT2 tumour angiogenesis and growth, while overexpression of the vascular endothelial growth factor (VEGF)-B increased tumour angiogenesis though tumour growth was impaired. In conclusion, we present a novel platform for intravital high-resolution and 3D imaging of PNET biology and cancer drug assessment.
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| 42. |
- Berggren, ChristianChrbe53, 1950-, et al.
(författare)
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Speeding up electro-mobility : How to electrify half of new car sales by 2030
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Noxious diesel emissions far above official limits and the need to rapidly reduce-greenhouse gases generate widespread calls for banning fossil-fueled cars in Europe. This report shows that it is possible to electrify 50 per cent of all new cars in the EU by 2030. This, however, requires massive investment in European battery production capacity, and a long-term commitment to sustainable supply of critical materials. In addition a large-scale expansion of the charging infrastructure is needed, in particular at home and at work places, which account for around 95 per cent of all battery charging. Moreover, local grids will need enforcement in most countries. The additional electricity demand must be satisfied at a time when many coal-fired and nuclear-based power plants will be decommissioned. Plug-in hybrids, which combine a downsized combustion engine with an electric motor, will probably play an important role, both to relieve long-distance drivers of range anxiety and to reduce the demand for scarce virgin metals, in particular cobalt. To make the shift happen, an EU-wide Zero Emission Vehicle (ZEV) mandate needs to be established from 2025, with planned stringency increases every second year or so. Such a regulation is less vulnerable to budget restraints and changing relative prices than financial incentives. At the same time, the regulatory demands on manufacturers to reduce CO2 emissions from combustions engines need to become more stringent and apply to all combustion engines, including those in plug-in hybrids. Such a combination of policies will make it possible to realize the overall target of 50 per cent electrification of new cars in a robust and flexible way.
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| 43. |
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| 44. |
- Berggren, Hanna
(författare)
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Consequences of Environmental Variation for Fish and Their Skin Associated Microbial Communities
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Environmental conditions that vary in space and time influence the distribution, abundance, diversity and evolution of individuals, populations, species and communities. This thesis explores how environmental variation affects diversity at different levels of biological organization, and across a wide range of spatiotemporal scales, by studying fish and their associated microbiomes. The specific aims were to investigate i) effects of coarse- and fine-scale environmental variation for the performance of fish populations and individuals, and ii) ecological drivers impacting the structure and dynamics of microbial communities associated with fish hosts.For the first aim, I studied effects of environmental variation both within and between local habitats, by comparing populations of spawning migrating pike and monitor sun-basking behaviour of carp individuals. Results revealed that natal spawning site fidelity can promote evolution of local adaptations and population differentiation on relatively fine spatial scales in relation to the species dispersal capacity. I also demonstrated that fish can actively thermo-regulate and attain body temperatures in excess of the surrounding water by sun-basking, and that this translates into faster growth. Homing and sun-basking behaviour thus are important drivers of phenotypic diversity among and within populations and can also - as it turned out - influence the microbial communities associated with fish skin.For the second aim, I used a mixture of observational and experimental approaches to characterize and identify sources of variation in microbial communities associated with fish skin of perch, roach and carp. An important finding was that fish skin microbiomes are highly dynamic biodiversity hotspots. Results further suggested that variation in the assembly, composition, spatial structure, and temporal shifts of these microbiomes are influenced by stochastic events in combination with ecological filtering imposed by environment and host phenotype, most notably behaviour. A key conclusion that emerges from this thesis is that diversity at one level of biological organisation seems to support and increase diversity at a higher hierarchical level of organisation. My thesis thus adds to the knowledge, and contribute new understanding and insight into, how environmental heterogeneity and the complex interplay between different species and hierarchical levels generate and maintain biodiversity.
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| 45. |
- Berggren, Hanna, et al.
(författare)
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Effects of environmental translocation and host characteristics on skin microbiomes of sun-basking fish
- 2023
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : Royal Society. - 0962-8452 .- 1471-2954. ; 290:2013
-
Tidskriftsartikel (refereegranskat)abstract
- Variation in the composition of skin-associated microbiomes has been attributed to host species, geographical location and habitat, but the role of intraspecific phenotypic variation among host individuals remains elusive. We explored if and how host environment and different phenotypic traits were associated with microbiome composition. We conducted repeated sampling of dorsal and ventral skin microbiomes of carp individuals (Cyprinus carpio) before and after translocation from laboratory conditions to a semi-natural environment. Both alpha and beta diversity of skin-associated microbiomes increased substantially within and among individuals following translocation, particularly on dorsal body sites. The variation in microbiome composition among hosts was significantly associated with body site, sun-basking, habitat switch and growth, but not temperature gain while basking, sex, personality nor colour morph. We suggest that the overall increase in the alpha and beta diversity estimates among hosts were induced by individuals expressing greater variation in behaviours and thus exposure to potential colonizers in the pond environment compared with the laboratory. Our results exemplify how biological diversity at one level of organization (phenotypic variation among and within fish host individuals) together with the external environment impacts biological diversity at a higher hierarchical level of organization (richness and composition of fish-associated microbial communities).
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| 46. |
- Berggren, Hanna, et al.
(författare)
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Fish skin microbiomes are highly variable among individuals and populations but not within individuals
- 2022
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Fish skin-associated microbial communities are highly variable among populations and species and can impact host fitness. Still, the sources of variation in microbiome composition, and particularly how they vary among and within host individuals, have rarely been investigated. To tackle this issue, we explored patterns of variation in fish skin microbiomes across different spatial scales. We conducted replicate sampling of dorsal and ventral body sites of perch (Perca fluviatilis) from two populations and characterized the variation of fish skin-associated microbial communities with 16S rRNA gene metabarcoding. Results showed a high similarity of microbiome samples taken from the left and right side of the same fish individuals, suggesting that fish skin microbiomes can be reliably assessed and characterized even using a single sample from a specific body site. The microbiome composition of fish skin differed markedly from the bacterioplankton communities in the surrounding water and was highly variable among individuals. No ASV was present in all samples, and the most prevalent phyla, Actinobacteria, Bacteroidetes, and Proteobacteria, varied in relative abundance among fish hosts. Microbiome composition was both individual- and population specific, with most of the variation explained by individual host. At the individual level, we found no diversification in microbiome composition between dorsal and ventral body sites, but the degree of intra-individual heterogeneity varied among individuals. To identify how genetic and phenotypic characteristics of fish hosts impact the rate and nature of intra-individual temporal dynamics of the skin microbiome, and thereby contribute to the host-specific patterns documented here, remains an important task for future research.
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| 47. |
- Berggren, Hanna, et al.
(författare)
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Testing for local adaptation to spawning habitat in sympatric subpopulations of northern pike by reciprocal translocation of embryos
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- We tested for local adaption in early life-history traits by performing a reciprocal translocation experiment with approximately 2500 embryos of pike (Esox lucius) divided in paired split-family batches. The experiment indicated local adaptation in one of the two subpopulations manifested as enhanced hatching success of eggs in the native habitat, both when compared to siblings transferred to a non-native habitat, and when compared to immigrant genotypes from the other subpopulation. Gene-by-environment effects on viability of eggs and larvae were evident in both subpopulations, showing that there existed genetic variation allowing for evolutionary responses to divergent selection, and indicating a capacity for plastic responses to environmental change. Next, we tested for differences in female life-history traits. Results uncovered that females from one population invested more resources into reproduction and also produced more (but smaller) eggs in relation to their body size compared to females from the other population. We suggest that these females have adjusted their reproductive strategies as a counter-adaptation because a high amount of sedimentation on the eggs in that subpopulations spawning habitat might benefit smaller eggs. Collectively, our findings point to adaptive divergence among sympatric subpopulations that are physically separated only for a short period during reproduction and early development – which is rare. These results illustrate how combinations of translocation experiments and field studies of life-history traits might infer about local adaptation and evolutionary divergence among populations. Local adaptations in subdivided populations are important to consider in management and conservation of biodiversity, because they may otherwise be negatively affected by harvesting, supplementation, and reintroduction efforts targeted at endangered populations.
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| 48. |
- Berggren, Jan, 1965-
(författare)
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Engelskundervisning i gymnasieskolan för mobilisering av ungdomars livschanser
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Berggren, Jan (2013). Engelskundervisning i gymnasieskolan för mobilisering av ungdomars livschanser. (English teaching in upper secondary school and mobilization of young people's life chances). Linnaeus University Dissertations No 156/2013, ISBN: 978-91-87427-64-0. Written in Swedish with a summary in English.English is a school subject which every Swedish upper secondary student is required to take. The selection and dissemination of knowledge among students attending upper secondary programmes carries the intention of social integration as well as specialization. The aim of this dissertation is then to show how perspectives on education in English elicited from teachers’ and students’ responses in interviews as well as Swedish education policy (SOU, directives, propositions) contribute to the conditions for the selection of knowledge and teaching, on and between programmes.Inspired by Basil Bernstein’s theories of educational sociology (1990, 2000) and Fairclough och Chouliaraki’s critical discourse analysis, CDA (1999), albeit adjusted to the aim of this study in pedagogics, the focus is on teachers’ and students’ views on teaching and knowledge in English classes on four vocational and academic programmes, establishing varying discourse practices on the different programmes. Moreover, perspectives on upper secondary teaching in Swedish education policy texts are analysed following the same methodology.Results indicate that education policy texts at the time of the interviews strive for adjustment of course content in English teaching to the programme (termed ‘infärgning’ in Swedish). Reflecting this trend in education policy, teachers and students on programmes speak of aspirations for English teaching as being either adapted for mainly academic purposes, or vocational and everyday-life purposes. On the basis of these aspirations it is argued that teachers and students establish either academically oriented discourse or vocational and everyday-life oriented discourse as the dominant pedagogical discourse on the individual programme. Thus, education policy as well as teachers and students reflect each other in striving for knowledge to be adapted for the programme. The two discourses contribute to a movement in favour of differences between programmes, though some of the vocational students complain on not being offered possibilities to analyse and discuss current problems in society. This is to say they complain that they do not receive an education in line with the academically oriented discourse, which is offered to students on academic programmes. At the same time, vocational students are dissatisfied in not gaining adequate knowledge in vocational English.Finally, these perspectives indicate discursive conditions for the selection of knowledge and the organization of teaching in English classes on different programmes. In the last chapter of the dissertation these varying perspectives on programmes concerning the selection of knowledge are analysed but now with a focus on the relationship between programmes. Consequences of the varying dominant pedagogical discourses on the programmes are discussed with regard to how they can be understood to mobilize life chances of young people differently, creating conditions for social integration and differentiation. Keywords: Selection of knowledge, upper secondary education, English, education policy, critical discourse analysis, sociology of education, social integration, social differentiation
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| 49. |
- Berggren, Kristina, et al.
(författare)
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Genetic engineering of protein-peptide fusions for control of protein partitioning in thermoseparating aqueous two-phase systems
- 1999
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Ingår i: Biotechnology and Bioengineering. - 1097-0290. ; 62:2, s. 135-144
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Tidskriftsartikel (refereegranskat)abstract
- Genetic engineering has been used for the fusion of peptides, with different length and composition, on a protein to study the effect on partitioning in aqueous two-phase systems containing thermoseparating polymers. Peptides containing 2-6 tryptophan residues or tryptophan plus 1-3 lysine or aspartate residues, were fused near the C-terminus of the recombinant protein ZZT0, where Z is a synthetic IgG-binding domain derived from domain B in staphylococcal protein A. The partitioning behavior of the peptides and fusion proteins were studied in an aqueous two-phase system composed of dextran and the thermoseparating ethylene oxide-propylene oxide random copolymer, EO30PO70. The zwitterionic compound beta-alanine was used to reduce the charge-dependent salt effects on partitioning, and to evaluate the contribution to the partition coefficient from the amino acid residues, Trp, Lys, and Asp, respectively. Trp was found to direct the fusion proteins to the EO-PO copolymer phase, while Asp and Lys directed them to the dextran phase. The effect of sodium perchlorate and triethylammonium phosphate on the partitioning of the fusion proteins was also studied. Salt effects were directly proportional to the net charge of the fusion proteins. Sodium perchlorate was found to be 3.5 times more effective in directing positively charged proteins to the EO-PO copolymer phase compared to the effect of triethyl ammonium phosphate on negatively charged proteins. An empirical correlation has been tested where the fusion protein partitioning is a result of independent contributions from unmodified protein, fused peptide, and salt effects. A good agreement with experimental data was obtained which indicates the possibility, by independent measurements of partitioning of target protein and fusion peptide, to approximately predict the fusion protein partitioning. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 62: 135-144, 1999.
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| 50. |
- Berggren, Karl, et al.
(författare)
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In vivo measurement of the effective atomic number of breast skin using spectral mammography
- 2018
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Ingår i: Physics in Medicine and Biology. - : Institute of Physics Publishing (IOPP). - 0031-9155 .- 1361-6560. ; 63:21
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Tidskriftsartikel (refereegranskat)abstract
- X-ray characteristics of body tissues are of crucial importance for developing and optimizing x-ray imaging techniques, in particular for dosimetry and spectral imaging applications. For breast imaging, the most important tissues are fibro-glandular, adipose and skin tissue. Some work has and is being done to better characterize these tissue types, in particular fibro-glandular and adipose tissue. In the case of breast skin, several recent studies have been published on the average skin thickness, but with regards to x-ray attenuation, the only published data, to the knowledge of the authors, is the elemental composition analysis of Hammerstein et al (1979 Radiology 130 485-91). This work presents an overview of breast skin thickness studies and a measurement of the effective atomic number (Z(eff)) of breast skin using spectral mammography. Z(eff), which together with the density forms the attenuation, is used to validate the work by Hammerstein et al, and the dependence of clinical parameters on Z(eff) is explored. Measurements were conducted on the skin edge of spectral mammograms using clinical data from a screening population (n = 709). The weighted average of breast skin thickness reported in studies between 1997 and 2013 was found to be 1.56 +/- 0.28 mm. Mean Z(eff) was found to be 7.365 (95% CI: 7.364,7.366) for normal breast skin and 7.441 (95% CI: 7.440,7.442) for the nipple and areola. Z(eff) of normal breast skin is in agreement with Hammerstein et al, despite the different methods and larger sample size used. A small but significant increase in Z(eff) was found with age, but the increase is too small to be relevant for most applications. We conclude that normal breast skin is well described by a 1.56 mm skin layer and the elemental composition presented by Hammerstein et al (1979 Radiology 130 485-91) and recommend using these characteristics when modelling breast skin.
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