| 1. |
- Ahlqvist, Emma, et al.
(författare)
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A link between GIP and osteopontin in adipose tissue and insulin resistance.
- 2013
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:6, s. 2088-2094
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Tidskriftsartikel (refereegranskat)abstract
- Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P<0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24, P=0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity. Carriers of the A-allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of GIPR rs10423928 A-allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.
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| 2. |
- Berglund, Lisa, et al.
(författare)
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Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 65:1, s. 239-254
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Tidskriftsartikel (refereegranskat)abstract
- Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.
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| 3. |
- Berglund, Lisa, et al.
(författare)
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Nuclear Factor of Activated T Cells Regulates Osteopontin Expression in Arterial Smooth Muscle in Response to Diabetes-Induced Hyperglycemia
- 2010
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Ingår i: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY. - Baltimore : Lippincott Williams & Wilkins. - 1079-5642. ; 30, s. 154-218
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Tidskriftsartikel (refereegranskat)abstract
- Objective-Hyperglycemia is a recognized risk factor for cardiovascular disease in diabetes. Recently, we reported that high glucose activates the Ca2+/calcineurin-dependent transcription factor nuclear factor of activated T cells (NFAT) in arteries ex vivo. Here, we sought to determine whether hyperglycemia activates NFAT in vivo and whether this leads to vascular complications. Methods and Results-An intraperitoneal glucose-tolerance test in mice increased NFATc3 nuclear accumulation in vascular smooth muscle. Streptozotocin-induced diabetes resulted in increased NFATc3 transcriptional activity in arteries of NFAT-luciferase transgenic mice. Two NFAT-responsive sequences in the osteopontin (OPN) promoter were identified. This proinflammatory cytokine has been shown to exacerbate atherosclerosis and restenosis. Activation of NFAT resulted in increased OPN mRNA and protein in native arteries. Glucose-induced OPN expression was prevented by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. The calcineurin inhibitor cyclosporin A or the novel NFAT blocker A-285222 prevented glucose-induced OPN expression. Furthermore, diabetes resulted in higher OPN expression, which was significantly decreased by in vivo treatment with A-285222 for 4 weeks or prevented in arteries from NFATc3(-/-) mice. Conclusions-These results identify a glucose-sensitive transcription pathway in vivo, revealing a novel molecular mechanism that may underlie vascular complications of diabetes.
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| 4. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 5. |
- Garcia-Vaz, Eliana, et al.
(författare)
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Inhibition of NFAT signaling restores microvascular endothelial function in diabetic mice
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:3, s. 424-435
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Tidskriftsartikel (refereegranskat)abstract
- Central to the development of diabetic macro- and microvascular disease is endothelial dysfunction, which appears well before any clinical sign but, importantly, is potentially reversible. We previously demonstrated that hyperglycemia activates nuclear factor of activated T cells (NFAT) in conduit and medium-sized resistance arteries and that NFAT blockade abolishes diabetes-driven aggravation of atherosclerosis. In this study, we test whether NFAT plays a role in the development of endothelial dysfunction in diabetes. NFAT-dependent transcriptional activity was elevated in skin microvessels of diabetic Akita (Ins21/2) mice when compared with nondiabetic littermates. Treatment of diabetic mice with the NFAT blocker A-285222 reduced NFATc3 nuclear accumulation and NFAT-luciferase transcriptional activity in skin microvessels, resulting in improved microvascular function, as assessed by laser Doppler imaging and iontophoresis of acetylcholine and localized heating. This improvement was abolished by pretreatment with the nitric oxide (NO) synthase inhibitor L-NGnitro-L-arginine methyl ester, while iontophoresis of the NO donor sodium nitroprusside eliminated the observed differences. A-285222 treatment enhanced dermis endothelial NO synthase expression and plasma NO levels of diabetic mice. It also prevented induction of inflammatory cytokines interleukin-6 and osteopontin, lowered plasma endothelin-1 and blood pressure, and improved mouse survival without affecting blood glucose. In vivo inhibition of NFAT may represent a novel therapeutic modality to preserve endothelial function in diabetes.
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| 6. |
- Gooding, Kim, et al.
(författare)
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Prognostic imaging biomarkers for diabetic kidney disease (iBEAt): study protocol
- 2020
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Ingår i: BMC Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). METHODS: iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m2. At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H2O15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. DISCUSSION: iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03716401 ).
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| 7. |
- Malmquist, Anna, 1981-, et al.
(författare)
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‘A daddy is the same as a mummy’ : Swedish children in lesbian households talk about fathers and donors
- 2014
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Ingår i: Childhood. - : Sage Publications. - 0907-5682 .- 1461-7013. ; 21:1, s. 119-133
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Tidskriftsartikel (refereegranskat)abstract
- The present article discusses how 12 children (five to eight years) in planned lesbian familiestalk about families, parents and specifically ‘daddies’ as such and not having a father themselves.Findings from child interviews demonstrate that the children described daddies as ‘the same’ asmummies, i.e. as having the same functions. This contrasts with previous research showing howchildren of heterosexuals often describe mothers and fathers as different. The children varied interms of how they labelled donors. Some children adopted the denomination ‘daddy’, drawing ona paternity discourse, while others simply referred to him as ‘a man’.
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| 8. |
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| 9. |
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| 10. |
- Virta, J, et al.
(författare)
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Impact of metabolic substrate modification on myocardial efficiency in a rat model of obesity and diabetes
- 2022
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Ingår i: European Heart Journal, Supplement. - : Oxford University Press (OUP). - 1520-765X .- 0195-668X .- 1522-9645. ; 43:2, s. 3076-3076
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Konferensbidrag (refereegranskat)abstract
- BackgroundCongenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but its effect on myocardial external efficiency, i.e. the ability of the myocardium to convert energy into external stroke work, remains uncertain.PurposeTo characterize cardiac energy metabolism and function in BBDR.lepr−/− rats and to study the effect of dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin in this model.MethodsCardiac phenotype was evaluated in six-month-old male BBDR.lepr−/− rats (n=11) and age-matched male non-diabetic lean control littermates (BBDR.lepr+/− or BBDR.lepr+/+ rats, n=14). Of these, 7 BBDR.lepr−/− rats and 6 controls underwent cardiac ultrasound, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), and [11C]acetate PET in order to evaluate cardiac structure and function as well as glucose and oxidative metabolism. In the remaining rats, fatty acid metabolism was evaluated by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) PET/CT. In the linagliptin intervention study, 25 BBDR.lepr−/− male rats were randomly divided into control group (n=11) that received regular chow diet and linagliptin group (n=14) that received linagliptin (10mg/kg/d) mixed in the chow diet for three months. After the intervention, the rats underwent cardiac ultrasound, [18F]FDG PET/CT, and [11C]acetate PET.ResultsCompared with controls, BBDR.lepr−/− rats showed increased left ventricle (LV) mass (∼40%, p>0.001) and higher systolic blood pressure (∼10%, p=0.02). However, fractional shortening and cardiac output were similar in both groups. Myocardial fractional uptake rate of glucose measured with [18F]FDG PET was significantly reduced (∼86%, p=0.004) (Fig. 1A, E), whereas myocardial fatty acid uptake measured by [18F]FTHA PET was not significantly increased (free fatty acid (FFA) corrected standardized uptake value (SUV) ∼21%, p=0.54) (Fig. 1B) in BBDR.lepr−/− compared to controls. Myocardial oxygen consumption assessed by [11C]acetate PET was similar in both groups (Fig. 1C, E), but LV work per gram of myocardium was reduced (∼28%, p=0.001) resulting in reduced myocardial external efficiency (∼21%, p=0.03) (Fig. 1D) in BBDR.lepr−/− compared to controls. Treatment with linagliptin significantly enhanced myocardial fractional uptake rate of glucose (∼166%, p=0.006) (Fig. 2A, C), but had no effect on efficiency of cardiac work (Fig. 2B).ConclusionsObese and diabetic BBDR.lepr−/− rats demonstrate LV hypertrophy and markedly reduced myocardial glucose utilization associated with impaired myocardial external efficiency despite normal LV systolic function. Enhancement of myocardial glucose uptake by linagliptin did not improve efficiency of cardiac work.Funding AcknowledgementType of funding sources: Public grant(s) – EU funding. Main funding source(s): IMI-SUMMIT
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| 11. |
- Zetterqvist, Anna, et al.
(författare)
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Inhibition of nuclear factor of activated T-cells (NFAT) suppresses accelerated atherosclerosis in diabetic mice.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis.
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| 12. |
- Awla, Darbaz, et al.
(författare)
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NFATc3 Regulates Trypsinogen Activation, Neutrophil Recruitment, and Tissue Damage in Acute Pancreatitis in Mice.
- 2012
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 143:5, s. 1352-1352
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The signaling mechanisms that regulate trypsinogen activation and inflammation in acute pancreatitis (AP) are unclear. We explored the involvement of the calcium- and calcineurin-dependent transcription factor nuclear factor of activated T-cells (NFAT) in development of AP in mice. METHODS: We measured levels of myeloperoxidase and macrophage inflammatory protein-2 (CXCL2), trypsinogen activation, and tissue damage in the pancreas 24 h after induction of AP by retrograde infusion of taurocholate into the pancreatic ducts of wild-type, NFAT luciferase reporter (NFAT-luc), and NFATc3-deficient mice. We isolated acinar cells and measured NFAT nuclear accumulation, trypsin activity, and expression of NFAT-regulated genes. RESULTS: Infusion of taurocholate increased the transcriptional activity of NFAT in the pancreas, aorta, lung, and spleen of NFAT-luc mice. Inhibition of NFAT with A-285222 blocked taurocholate-induced activation of NFAT in all organs. A-285222 also reduced taurocholate-induced increases in levels of amylase, myeloperoxidase and CXCL2; activation of trypsinogen; necrosis of acinar cells; edema; leukocyte infiltration; and hemorrhage in the pancreas. NFATc3-deficient mice were protected from these effects of taurocholate. Similar results were obtained using an L-arginine-induced model of AP. Reverse transcriptase PCR and confocal immunofluorescence analyses showed that NFATc3 is expressed by acinar cells. NFATc3 expression was activated by stimuli that increase intracellular calcium; activation was prevented by the calcineurin blocker cyclosporine A or A-285222. Activation of trypsinogen by secretagogues in acinar cells was prevented by pharmacologic inhibition of NFAT signaling or lack of NFATc3. A-285222 also reduced expression of inflammatory cytokines such as CXCL2 in acinar cells. CONCLUSIONS: NFATc3 regulates trypsinogen activation, inflammation, and pancreatic tissue damage during development of AP in mice, and might be a therapeutic target.
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| 13. |
- Berglund, Lisa, et al.
(författare)
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Nuclear factor of activated T-cells transcription factors in the vasculature: the good guys or the bad guys?
- 2008
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Ingår i: Current Opinion in Lipidology. - 1473-6535. ; 19:5, s. 483-490
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: The nuclear factor of activated T-cells (NFAT) proteins are a family of Ca/calcineurin-dependent transcription factors that were first characterized in T-lymphocytes as inducers of cytokine gene expression. Since then, NFAT proteins have been shown to play varied roles outside of the immune system, including in the cardiovascular system. Cells in the vessel wall display a diverse array of Ca signaling modalities, which are subject to change during disease. The fact that NFAT proteins are able to decode and translate these signals into changes in gene expression makes them potential regulators of vascular pathogenesis. RECENT FINDINGS: It is now clear that NFAT signaling is required for normal vascular patterning during embryogenesis and for vascular endothelial growth factor-induced angiogenesis. The overall role of NFAT signaling in the vasculature, however, is less clear during adult life. This review aims to give an update on mechanisms that regulate NFAT activation in vascular cells, with an emphasis on the role of mitochondria and of upstream activators such as lipids and glucose. It also addresses recent work implicating NFAT proteins as mediators of vascular disease. SUMMARY: A better understanding of the NFAT-signaling pathway in the vasculature may open up an unexplored area for the development of new therapeutic approaches for treating vascular disease.
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| 14. |
- Gustavsson, Carin, et al.
(författare)
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Vascular cellular adhesion molecule-1 (VCAM-1) expression in mice retinal vessels is affected by both hyperglycemia and hyperlipidemia.
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inflammation has been proposed to be important in the pathogenesis of diabetic retinopathy. An early feature of inflammation is the release of cytokines leading to increased expression of endothelial activation markers such as vascular cellular adhesion molecule-1 (VCAM-1). Here we investigated the impact of diabetes and dyslipidemia on VCAM-1 expression in mouse retinal vessels, as well as the potential role of tumor necrosis factor-α (TNFα). METHODOLOGY/PRINCIPAL FINDINGS: Expression of VCAM-1 was examined by confocal immunofluorescence microscopy in vessels of wild type (wt), hyperlipidemic (ApoE(-/-)) and TNFα deficient (TNFα(-/-), ApoE(-/-)/TNFα(-/-)) mice. Eight weeks of streptozotocin-induced diabetes resulted in increased VCAM-1 in wt mice, predominantly in small vessels (<10 µm). Diabetic wt mice had higher total retinal TNFα, IL-6 and IL-1β mRNA than controls; as well as higher soluble VCAM-1 (sVCAM-1) in plasma. Lack of TNFα increased higher basal VCAM-1 protein and sVCAM-1, but failed to up-regulate IL-6 and IL-1β mRNA and VCAM-1 protein in response to diabetes. Basal VCAM-1 expression was higher in ApoE(-/-) than in wt mice and both VCAM-1 mRNA and protein levels were further increased by high fat diet. These changes correlated to plasma cholesterol, LDL- and HDL-cholesterol, but not to triglycerides levels. Diabetes, despite further increasing plasma cholesterol in ApoE(-/-) mice, had no effects on VCAM-1 protein expression or on sVCAM-1. However, it increased ICAM-1 mRNA expression in retinal vessels, which correlated to plasma triglycerides. CONCLUSIONS/SIGNIFICANCE: Hyperglycemia triggers an inflammatory response in the retina of normolipidemic mice and up-regulation of VCAM-1 in retinal vessels. Hypercholesterolemia effectively promotes VCAM-1 expression without evident stimulation of inflammation. Diabetes-induced endothelial activation in ApoE(-/-) mice seems driven by elevated plasma triglycerides but not by cholesterol. Results also suggest a complex role for TNFα in the regulation of VCAM-1 expression, being protective under basal conditions but pro-inflammatory in response to diabetes.
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| 15. |
- Holmqvist Larsson, Kristina, et al.
(författare)
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Emotion regulation group skills training: a pilot study of an add-on treatment for eating disorders in a clinical setting
- 2020
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Ingår i: Journal of Eating Disorders. - : BMC. - 2050-2974. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Emotion regulation difficulties appear to play a role in the development and maintenance of several eating disorders. This pilot study aimed at examining whether a short add-on group skills training in emotion regulation for young adults with different eating disorders was feasible in a psychiatric clinical setting. We also investigated if the treatment increased knowledge of emotions, and decreased self-reported difficulties with emotion regulation, alexithymia, symptoms of eating disorder, anxiety and depression, as well as clinical impairment. Methods Six skills training groups were piloted with a total of 29 participants (M = 21.41 years, SD = 1.92). The treatment consisted of five sessions dealing with psychoeducation about emotions and emotion regulation skills training. Paired samples t-test was used to compare differences between before-and-after measures. Results The primary outcomes measures difficulties in emotion regulation (p < 0.001) and alexithymia (p < 0.001) showed significant improvement after treatment. The total eating disorder score (p = 0.009) was also significantly reduced, as was clinical impairment (p < 0.001). Acceptance/valued direction, identifying primary emotions and learning about secondary emotions was rated as especially helpful. Conclusions This preliminary pilot study showed that group training targeting emotion regulation skills was feasible and appreciated by participants, as well as being potentially promising as an adjunctive treatment for different eating disorders. Further controlled studies are needed.
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| 16. |
- Josefsson, Jonathan
(författare)
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Children at the Borders
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the wake of a steady flow of child migrants attempting to cross borders and states’ efforts to restrict immigration, various public controversies have arisen about the rights of asylum-seeking children. The ‘moral gap’ between the outcome of democratically enacted laws and the aim of controlling immigration, on the one hand, and public calls to protect the universal rights of asylum seeking children, on the other, have created a political challenge for Western democracies. This thesis sets out to examine two particular settings in which norms about the rights of asylum-seeking children and immigration control have been established and contested over the years: the Swedish Migration Court of Appeal and Sweden’s largest morning paper, Dagens Nyheter. It combines empirically oriented analysis with theoretical enquiry, and it brings the issue of the rights of asylumseeking children into dialogue with the contemporary political-philosophical debate about membership, rights and borders.
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| 17. |
- Lundberg, Anna, et al.
(författare)
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Barndom, kultur och politik : ett teaterpolitiskt forskningsprojekt. Forskarnas rapport
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Föreliggande rapport sammanfattar reflektioner och tentativa slutsatser från ett samarbetsprojekt mellan ung scen/öst och tema Barn, Linköpings universitet under år 2011. Målet med verksamheten var tredelat och syftade till 1) att utveckla samarbete mellan forskning och konstnärlig verksamhet genom en modell byggd på metoden aktionsforskning, 2) att forskarna skulle återkoppla sina iakttagelser under repetitionsarbetet med betoning på att det skulle ske innan premiären, 3) att dramatikerna också önskade sig en kritisk analys av pjäsen som text. Forskarna har utforskat iscensättningsprocessen,reflekterat och analyserat återkopplingsprocesser mellan forskare och dramatiker, samt genomfört en genusteoretisk textläsning av pjäsen. Rapporten speglar dessa tre aspekter av samarbetet.
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| 18. |
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| 19. |
- Malmquist, Anna, 1981-, et al.
(författare)
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Efforts to maintain a ’just great’ story : Lesbian parents’ talk about encounters with professionals in fertility clinics and maternal and child healthcare services
- 2014
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Ingår i: Feminism and Psychology. - : Sage Publications. - 0959-3535 .- 1461-7161. ; 24:1, s. 56-73
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Tidskriftsartikel (refereegranskat)abstract
- After lesbian couples have decided to become parents, their family-making journeyentails a wide range of encounters with professionals in fertility clinics and/or in maternaland child healthcare services. The article presents the results of an analysis of 96lesbian mothers’ interview talk about such encounters. In their stories and accounts,the interviewees draw on two separate and contradictory interpretative repertoires,the ‘just great’ repertoire and the ‘heteronormative issues’ repertoire. Throughout theinterviews, the ‘just great’ repertoire strongly predominates, while the ‘heteronormativeissues’ repertoire is rhetorically minimized. The recurrent accounts of health servicesas ‘just great’, and the mitigation of problems, are meaningful in relation to abroader discursive context. In a society where different-sex parents are the norm,the credibility of other kinds of parenthood is at stake. The ‘just great’ repertoire hasa normalizing function for lesbian mothers, while the ‘heteronormative issues’ repertoireresists normative demands for adaptation.
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| 20. |
- Malmquist, Anna, et al.
(författare)
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Familjeliv hos samkönade par och andra regnbågsfamiljer
- 2012. - 2
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Ingår i: Nätverksfamiljen. - Stockholm : Natur och kultur. - 9789127133044 ; , s. 139-157
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Kärnfamiljen är fortfarande den vanligaste samlevnadsformen i vårt land men samhällstrenden visar på en allt större variation i samlevnadsmönster. Familjer bryter upp och nya par flyttar samman. Med barnen som länkar bildas nätverk av relationer. Den senmoderna familjen utgör en nätverksfamilj. Med nätverket som metafor upplöses familjen som en sluten social enhet.I stället ställs relationerna och det vardagliga familjelivet i fokus.Invanda levnadsmönster, traditionella roller och könsidentiteter utmanas och ifrågasätts. Uppbrotten kan även splittra familjer mellan länder och världsdelar. Vad är en familj? Vilka familjekonstellationer är tänkbara? Hur påverkar de nya strukturerna barns och föräldrars roller? Denna bok skildrar samtidens mångfald i samlevnadsformer, t ex den traditionella kärnfamiljen, nya familjebildningar med styvföräldrar och egna samt gemensamma barn, ensam mor-familjen, heltids-eller deltidspappan, den homosexuella familjen och den inflyttade familjen från en annan kultur.I bokens andra del fördjupas resonemangen kring det nya fader- och moderskapet, fosterfamiljen, den utsatta familjen, våld i familjen och problematik kring barnlöshet. Boken vill beskriva och analysera hur män och kvinnor i nya familjemönster praktiskt utformar föräldraskap, parförhållande liksom ansvar för och omsorg om familjen. Familjen skapas genom sina vardagshandlingar. Boken riktar sig till studerande i socialt arbete, sociologi och andra samhällsvetenskapliga ämnen på universitet och högskola men också till yrkesverksamma inom socialt arbete, vård och inom andra sektorer av det samhällspolitiska området. Margareta Bäck-Wiklund (red) är professor i socialt arbete med inriktning på familjepolitik och modernt föräldraskap vid institutionen för socialt arbete, Göteborgs universitet. Thomas Johansson (red) är professor i socialpsykologi och verksam vid institutionen för socialt arbete vid Göteborgs universitet med inriktning på familjesociologi och mansforskning. Båda har tidigare publicerat en rad böcker och artiklar inom sina områden. Bokens övriga kapitelförfattare är forskare inom framför allt områdena socialt arbete och sociologi men även inom psykologi och etnologi: Maren Bak, Helene Brembeck, Gunilla Halldén, Sven Hessle, Margareta Hydén, Ingrid Höjer, Anders Möller, Karin Zetterqvist Nelson, Eva Nyberg, Lars Plantin, Christine Roman, Kristina Larsson Sjöberg och Jan Trost .
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| 21. |
- Malmquist, Anna, 1981-, et al.
(författare)
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Gay and Lesbian Parents
- 2013
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Ingår i: Oxford Bibliographies in Childhood Studies.. - New York : Oxford University Press.
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Forskningsöversikt (refereegranskat)
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| 22. |
- Malmquist, Anna
(författare)
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Pride and Prejudice : Lesbian Families in Contemporary Sweden
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Options and possibilities for lesbian parents have changed fundamentally since the turn of the millennium. A legal change in 2003 enabled a same-sex couple to share legal parenthood of the same child. An additional legal change, in 2005, gave lesbian couples access to fertility treatment within public healthcare in Sweden. The present thesis focuses on families where two women share legal parenthood of their children. It aims to provide knowledge about lesbian parenting couples and their children, and to focus on the interplay between family members within lesbian families, and between family members and their surroundings. Furthermore, the thesis aims to visualize and analyse notions of heteronormativity and homonormativity in contemporary Sweden. The thesis draws on interviews with 118 parents in 61 families, and 12 children in 11 families. The participants’ stories, descriptions, reflections and discourses have been analysed using discursive psychology and thematic analysis.The thesis includes five empirical papers. Paper I focuses on encounters with healthcare professionals prior to and during pregnancy, at childbirth and during the early stages of parenthood. Paper II deals with the participants’ experiences of second-parent adoption processes. Paper III focuses on equality in parenting relations. Paper IV focuses on encounters with fertility clinics within public healthcare. Paper V highlights the children’s reflections and shows how the children talk about fathers and donors.
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| 24. |
- Parzych, Katarzyna, et al.
(författare)
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Differential role of pannexin-1/ATP/P2X7 axis in IL-1β release by human monocytes
- 2017
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Ingår i: FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 31:6, s. 2439-2445
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Tidskriftsartikel (refereegranskat)abstract
- IL-1β release is integral to the innateimmunesystem.The release ofmature IL-1βdepends on 2 regulated events: the de novo induction of pro-IL-1β, generally via NF-κB-dependent transduction pathways; and the assembly and activation of the NLRP3 inflammasome. This latter step is reliant on active caspase-1, pannexin-1, and P2X7 receptor activation. Pathogen-associated molecular patterns in gram-positive and gram-negative bacteria activate IL-1β release from immune cells via TLR2 and TLR4 receptors, respectively. We found that pro-IL-1β and mature IL-1β release fromhumanmonocytes is stimulated by the TLR2 agonists Pam3CSK4 or FSL-1, as well as the TLR4agonist LPSin the absence of additionalATP.TLR2agonists requiredpannexin-1 and P2X7 receptor activation to stimulate IL-1β release. In contrast, IL-1β release stimulated by the TLR4 agonist LPS is independent of both pannexin-1 and P2X7 activation. In the absenceof exogenousATP,P2X7 activationrequires endogenousATPrelease, which occurs in some cells via pannexin-1. In line with this, we found that LPS-stimulated human monocytes released relatively low levels of ATP, whereas cells stimulated with TLR2 agonists released high levels of ATP. These findings suggest that in humanmonocytes, both TLR2 and TLR4 signaling induce pro-IL-1β expression, but themechanismbywhich they activate caspase-1diverges at the level of thepannexin-1/ATP/P2X7 axis.
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| 26. |
- Zetterqvist, Anna, et al.
(författare)
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Complaints, Complainants, and Rulings Regarding Drug Promotion in the United Kingdom and Sweden 2004–2012: A Quantitative and Qualitative Study of Pharmaceutical Industry Self-Regulation
- 2015
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1676. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Background In many European countries, medicines promotion is governed by voluntary codes of practice administered by the pharmaceutical industry under its own system of self-regulation. Involvement of industry organizations in policing promotion has been proposed to deter illicit conduct, but few detailed studies on self-regulation have been carried out to date. The objective of this study was to examine the evidence for promotion and self-regulation in the UK and Sweden, two countries frequently cited as examples of effective self-regulation. Methods and Findings We performed a qualitative content analysis of documents outlining the constitutions and procedures of these two systems. We also gathered data from self-regulatory bodies on complaints, complainants, and rulings for the period 2004–2012. The qualitative analysis revealed similarities and differences between the countries. For example, self-regulatory bodies in both countries are required to actively monitor promotional items and impose sanctions on violating companies, but the range of sanctions is greater in the UK where companies may, for instance, be audited or publicly reprimanded. In total, Swedish and UK bodies ruled that 536 and 597 cases, respectively, were in breach, equating to an average of more than one case/week for each country. In Sweden, 430 (47%) complaints resulted from active monitoring, compared with only two complaints (0.2%) in the UK. In both countries, a majority of violations concerned misleading promotion. Charges incurred on companies averaged €447,000 and €765,000 per year in Sweden and the UK, respectively, equivalent to about 0.014% and 0.0051% of annual sales revenues, respectively. One hundred cases in the UK (17% of total cases in breach) and 101 (19%) in Sweden were highlighted as particularly serious. A total of 46 companies were ruled in breach of code for a serious offence at least once in the two countries combined (n = 36 in the UK; n = 27 in Sweden); seven companies were in serious violation more than ten times each. A qualitative content analysis of serious violations pertaining to diabetes drugs (UK, n = 15; Sweden, n = 6; 10% of serious violations) and urologics (UK, n = 6; Sweden, n = 13; 9%) revealed various types of violations: misleading claims (n = 23; 58%); failure to comply with undertakings (n = 9; 23%); pre-licensing (n = 7; 18%) or off-label promotion (n = 2; 5%); and promotion of prescription drugs to the public (n = 6; 15%). Violations that go undetected or unpunished by self-regulatory bodies are the main limitation of this study, since they are likely to lead to an underestimate of industry misconduct. Conclusions The prevalence and severity of breaches testifies to a discrepancy between the ethical standard codified in industry Codes of Conduct and the actual conduct of the industry. We discuss regulatory reforms that may improve the quality of medicines information, such as pre-vetting and intensified active monitoring of promotion, along with larger fines, and giving greater publicity to rulings. But despite the importance of improving regulatory arrangements in an attempt to ensure unbiased medicines information, such efforts alone are insufficient because simply improving oversight and increasing penalties fail to address additional layers of industry bias.
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| 27. |
- Zetterqvist, Anna, et al.
(författare)
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Misleading advertising for antidepressants in sweden: a failure of pharmaceutical industry self-regulation.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- The alleged efficacy of pharmaceutical industry self-regulation has been used to repudiate increased government oversight over promotional activity. European politicians and industry have cited Sweden as an excellent example of self-regulation based on an ethical code. This paper considers antidepressant advertising in Sweden to uncover the strengths and weaknesses of self-regulation.
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| 28. |
- Zetterqvist, Anna
(författare)
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NFAT signaling in chronic and acute inflammation - A novel target for the treatment of diabetic vascular complications and acute pancreatitis?
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diabetic patients suffer from macro- and microvascular complications causing increased morbidity and mortality. How hyperglycemia provokes vascular damage remains unclear, but glucose is believed to fuel a harmful low-grade chronic inflammation of the vessel wall. Previous work showed that glucose activates the transcription factor Nuclear Factor of Activated T cells (NFAT) in arteries ex vivo. NFAT is a family of Ca2+-calcineurin-sensitive proteins first found to regulate inflammatory gene expression in T cells, but have since been demonstrated to play a role in other cell types, including vascular endothelium and smooth muscle cells. We hypothesized that NFAT proteins are activated by glucose in diabetic vessels where they regulate proinflammatory genes that contribute to diabetic atherosclerosis and retinopathy. We also hypothesized that NFAT proteins regulate the inflammatory disease acute pancreatitis (AP). In the thesis, we demonstrate that both acute and chronic hyperglycemia activate NFAT in large arteries and retinal microvessels of mice. We show that activation of NFAT promotes the expression of the pro-inflammatory cytokine osteopontin (OPN). In vivo inhibition of NFAT with the novel blocker A-285222 or genetic deletion of NFATc3 reduced diabetes-induced OPN expression in mouse aorta. Moreover, we showed that treatment with A-285222 abolished diabetes-induced atherosclerosis, but had no effect on atherosclerosis in non-diabetic mice. Specifically, A-285222 reduced aortic lipid and macrophage content and the expression of IL-6, OPN, monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), and tissue factor in the arterial wall. In retinal vessels in vivo, we show that both glucose and lipids up-regulate the expression of vascular cell adhesion molecule 1 ( VCAM-1), promoting endothelial activation. Furthermore, in these vessels, we demonstrate that NFAT is activated by glucose by a mechanism involving the local release of extracellular nucleotides (i.e. UTP, UDP). In vivo inhibition of NFAT prevented diabetes-induced reduction of anti-inflammatory IL-10 in whole retina and reduced OPN and ICAM-1 mRNA in retinal microvessels. Finally, in the context of the exocrine pancreas, we demonstrate that NFATc3 regulates trypsinogen activation, inflammation and tissue damage in two mouse models of AP, and that NFATc3 deletion prevents AP-induced damage. Taken together, this thesis establishes that NFAT plays important roles in diabetic vascular complications and AP. Targeting NFAT may represent a novel therapeutic approach in these inflamatory disorders.
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| 29. |
- Zetterqvist, Anna, et al.
(författare)
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Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice.
- 2015
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Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor. Endothelial dysfunction and changes in Ca(2+) signaling have been shown to precede the onset of DR. We recently demonstrated that high extracellular glucose activates the Ca(2+)/calcineurin-dependent transcription factor NFAT in cerebral arteries and aorta, promoting the expression of inflammatory markers. Here we show, using confocal immunofluorescence, that NFAT is expressed in the endothelium of retinal microvessels and is readily activated by high glucose. This was inhibited by the NFAT blocker A-285222 as well as by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. Acute hyperglycemia induced by an IP-GTT (intraperitoneal glucose tolerance test) resulted in increased NFATc3 nuclear accumulation and NFAT-dependent transcriptional activity in retinal vessels of NFAT-luciferase reporter mice. In both Akita (Ins2(+/-) ) and streptozotocin- (STZ-) induced diabetic mice, NFAT transcriptional activity was elevated in retinal vessels. In vivo inhibition of NFAT with A-285222 decreased the expression of OPN and ICAM-1 mRNA in retinal vessels, prevented a diabetes driven downregulation of anti-inflammatory IL-10 in retina, and abrogated the increased vascular permeability observed in diabetic mice. Results identify NFAT signaling as a putative target for treatment of microvascular complications in diabetes.
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| 30. |
- Zetterqvist Nelson, Karin, 1960-, et al.
(författare)
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Assisterad befruktning för lesbiska par : Gayvänligt, heteronormativt eller både och?
- 2011
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Ingår i: Föräldraskapets politik. - Stockholm : Dialogos Förlag. - 9789175042381 ; , s. 129-149
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Under de senaste hundra åren har betydelsen av goda familjeförhållanden och gott föräldraskap betonats allt mer i debatt och politik. Men vad utgör ett gott föräldraskap, och hur skapas goda mödrar och fäder? Svaret på dessa frågor förändrats under det senaste seklet.Såväl föräldraskapet självt som försöken att påverka det genomgår ständiga förändringar. Adoptionsutredningar, assisterad befruktning för lesbiska par samt föräldrars engagemang i sina barns skolgång är några av de frågor som i boken får belysa samhällsutvecklingen. Att vara förälder till ett barn kan tyckas vara en naturlig och ursprunglig relation, men påverkas i högsta grad av tid, plats och sociala villkor.Bokens författare är historiker och samhällsvetare verksamma vid olika universitet och högskolor runt om i Sverige.
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