| 1. |
- Ankarberg, Peter, et al.
(author)
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Socialstyrelsens riktlinjer är partiska och ovetenskapliga!
- 2017
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In: Psykoterapi. - 2001-5836. ; 26:2, s. 30-34
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Journal article (pop. science, debate, etc.)abstract
- Denna artikel är ett remissvar med synpunkter på de nationella riktlinjerna för ångest och depression, som vi publicerar i sin helhet i tidskriften. Vi gör det på grund av den ingående kunskap om processerna i riktlinjearbetet som några av författarna har kunnat få genom egen medverkan och närvaro i det arbetet.
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| 2. |
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| 3. |
- Chowdhury, Azazul Islam
(author)
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Role of Cell-cell Interactions and Palmitate on β-cells Function
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The islets of Langerhans secrets insulin in response to fluctuations of blood glucose level and efficient secretion requires extensive intra-islet communication. Secretory failure from islets is one of the hallmark in progression of type 2 diabetes. Changes in islet structure and high levels of saturated free fatty acids may contribute to this failure. The aim of this thesis is to study the role of cell-cell interactions and palmitate on β-cells functions.To address the role of cell-cell interactions on β-cells functions MIN6 cells were cultured as monolayers and as pseudoislets. Glucose stimulated insulin secretion was higher in pseudoislets compared to monolayers. Transcript levels of mitochondrial metabolism as well glucose oxidation rate was higher in pseudoislets. Insulin receptor substrate-1 (IRS-1) phosphorylation was altered when cells were grown as pseudoislets. Proteins expression levels related to glycolysis, cellular connections and translational regulations were up-regulated in pseudoislets. We propose the superior capacity of pseudoislets compared to monolayers depend on metabolism, cell coupling, gene translation, protein turnover and differential IRS-1 phosphorylation.To address the role of palmitate on β-cells human islets were cultured in palmitate. Long term palmitate treatment decreased insulin secretion which is associated with up-regulation of suppressor of cytokine signaling-2 (SOCS2) and protein inhibitor of activated STAT-1 (PIAS1). Up-regulation of SOCS2 decreased phosphorylation of Akt at site T308, whereas PIAS1 decreased protein level of ATP- citrate lyase (ACLY) and ATP synthase subunit B (ATP5B). We propose long term palmitate treatment reduces phosphatidylinositol 3-kinase (PI3K) activity, attenuates formation of acetyl-CoA and decreases ATP synthesis which may aggravate β-cells dysfunction.
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| 4. |
- Persaud, Shanta J., et al.
(author)
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Pseudoislets as primary islet replacements for research Report on a symposium at King's College London, London UK
- 2010
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In: Islets. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 2:4, s. 236-239
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Journal article (other academic/artistic)abstract
- Laboratory-based research aimed at understanding processes regulating insulin secretion and mechanisms underlying beta-cell dysfunction and loss in diabetes often makes use of rodents, as these processes are in many respects similar between rats/mice and humans. Indeed, a rough calculation suggests that islets have been isolated from as many as 150,000 rodents to generate the data contained within papers published in 2009 and the first four months of 2010. Rodent use for islet isolation has been mitigated, to a certain extent, by the availability of a variety of insulin-secreting cell lines that are used by researchers world-wide. However, when maintained as monolayers the cell lines do not replicate the robust, sustained secretory responses of primary islets which limits their usefulness as islet surrogates. On the other hand, there have been several reports that configuration of MIN6 beta-cells, derived from a mouse insulinoma, as three-dimensional cell clusters termed 'pseudoislets' largely recapitulates the function of primary islet beta-cells. The Diabetes Research Group at King's College London has been using the MIN6 pseudoislet model for over a decade and they hosted a symposium on "Pseudoislets as primary islet replacements for research", which was funded by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), in London on 15(th) and 16(th) April 2010. This small, focused meeting was conceived as an opportunity to consolidate information on experiences of working with pseudoislets between different UK labs, and to introduce the theory and practice of pseudoislet culture to laboratories working with islets and/or beta-cell lines but who do not currently use pseudoislets. This short review summarizes the background to the development of the cell line-derived pseudoislet model, the key messages arising from the symposium and emerging themes for future pseudoislet research.
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| 5. |
- Abadpour, S., et al.
(author)
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Inhibition of the prostaglandin D-2-GPR44/DP2 axis improves human islet survival and function
- 2020
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63, s. 1355-1367
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D-2 (PGD(2)) receptor, GPR44/DP2, is highly expressed in human islets and activation of the pathway results in impaired insulin secretion. The role of GPR44 activation on islet function and survival rate during chronic hyperglycaemic conditions is not known. In this study, we investigate GPR44 inhibition by using a selective GPR44 antagonist (AZ8154) in human islets both in vitro and in vivo in diabetic mice transplanted with human islets. Methods Human islets were exposed to PGD(2) or proinflammatory cytokines in vitro to investigate the effect of GPR44 inhibition on islet survival rate. In addition, the molecular mechanisms of GPR44 inhibition were investigated in human islets exposed to high concentrations of glucose (HG) and to IL-1 beta. For the in vivo part of the study, human islets were transplanted under the kidney capsule of immunodeficient diabetic mice and treated with 6, 60 or 100 mg/kg per day of a GPR44 antagonist starting from the transplantation day until day 4 (short-term study) or day 17 (long-term study) post transplantation. IVGTT was performed on mice at day 10 and day 15 post transplantation. After termination of the study, metabolic variables, circulating human proinflammatory cytokines, and hepatocyte growth factor (HGF) were analysed in the grafted human islets. Results PGD(2) or proinflammatory cytokines induced apoptosis in human islets whereas GPR44 inhibition reversed this effect. GPR44 inhibition antagonised the reduction in glucose-stimulated insulin secretion induced by HG and IL-1 beta in human islets. This was accompanied by activation of the Akt-glycogen synthase kinase 3 beta signalling pathway together with phosphorylation and inactivation of forkhead box O-1and upregulation of pancreatic and duodenal homeobox-1 and HGF. Administration of the GPR44 antagonist for up to 17 days to diabetic mice transplanted with a marginal number of human islets resulted in reduced fasting blood glucose and lower glucose excursions during IVGTT. Improved glucose regulation was supported by increased human C-peptide levels compared with the vehicle group at day 4 and throughout the treatment period. GPR44 inhibition reduced plasma levels of TNF-alpha and growth-regulated oncogene-alpha/chemokine (C-X-C motif) ligand 1 and increased the levels of HGF in human islets. Conclusions/interpretation Inhibition of GPR44 in human islets has the potential to improve islet function and survival rate under inflammatory and hyperglycaemic stress. This may have implications for better survival rate of islets following transplantation.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Andersson, Christina, et al.
(author)
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Cultivating Compassion and Reducing Stress and Mental Ill-Health in Employees : A Randomized Controlled Study
- 2022
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In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 12
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Journal article (peer-reviewed)abstract
- Stress and mental ill-health carry considerable costs for both individuals and organizations. Although interventions targeting compassion and self-compassion have been shown to reduce stress and benefit mental health, related research in organizational settings is limited. We investigated the effects of a 6-week psychological intervention utilizing compassion training on stress, mental health, and self-compassion. Forty-nine employees of two organizations were randomly assigned to either the intervention (n = 25) or a physical exercise control condition (n = 24). Multilevel growth models showed that stress (p = 0.04) and mental ill-health (p = 0.02) decreased over 3 months in both groups (pre-intervention to follow-up: Cohen’s d = −0.46 and d = 0.33, respectively), while self-compassion only increased in the intervention group (p = 0.03, between group d = 0.53). There were no significant effects on life satisfaction in any of the groups (p > 0.53). The findings show promising results regarding the ability of compassion training within organizations to decrease stress and mental ill-health and increase self-compassion.
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| 10. |
- Andersson, Christina, et al.
(author)
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The effectiveness of smartphone compassion training on stress among Swedish university students : A pilot randomized trial
- 2021
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In: Journal of Clinical Psychology. - : John Wiley & Sons. - 0021-9762 .- 1097-4679. ; 77:4, s. 927-945
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Journal article (peer-reviewed)abstract
- Objective: To investigate the effects of a 6-week smartphone compassion training intervention on mental health.Method: Fifty-seven Swedish university students (mean age = 25, SD = 5) reporting high levels of stress were randomized to compassion training (n = 23), mindfulness (n = 19), or waitlist (n = 15).Result: Multilevel models indicated that both compassion and mindfulness training increased self-compassion compared to the waitlist, while only compassion significantly reduced stress. Between-group effect sizes for compassion compared to waitlist were large for both self-compassion (d = 1.61) and stress (d = 0.94). Compassion and mindfulness did not differ significantly, but effect sizes were in favor of compassion. Secondary outcomes indicated positive effects on emotional awareness, while no effect was found for global psychological distress.Conclusions: Our results suggest that compassion training via a smartphone application can improve self-compassion and reduce stress among university students. Future studies in larger clinical samples are warranted.
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| 11. |
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| 12. |
- Aydin, Banu K., et al.
(author)
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High levels of FSH before puberty are associated with increased risk of metabolic syndrome during pubertal transition
- 2022
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In: Pediatric Obesity. - : John Wiley & Sons. - 2047-6302 .- 2047-6310. ; 17:8
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Journal article (peer-reviewed)abstract
- Background During perimenopause, the rise in serum follicle-stimulating hormone (FSH) is associated with increased adiposity, insulin resistance (IR), and metabolic syndrome (MetS). However, data for the pubertal period, which is characterized by increasing FSH levels and changing body composition, are limited. Objectives To investigate the relationships between FSH and anthropometric changes, IR markers, and development of MetS in the peripubertal period. Methods Uppsala Longitudinal Study of Childhood Obesity (ULSCO) is an ongoing study that aims to understand the factors contributing to childhood obesity and the development of obesity-related diseases. We analysed the subset of participants who were prepubertal at the first visit (n = 95, 77 with obesity). Mean follow-up time was 3.0 +/- 1.4 years. Results Higher serum FSH levels at the first visit were associated with an increased likelihood of elevation in body mass index (BMI SDS) (p = 0.025, OR = 16.10) and having MetS (p = 0.044, OR = 4.67) at the follow-up. We observed nonlinear relationships between varying serum FSH levels and markers of adiposity and IR, especially in girls. At the first visit, when girls were prepubertal, FSH was negatively associated with BMI (beta = -0.491, p = 0.005) and positively associated with sex hormone-binding globulin (SHBG) (beta = 0.625, p = 0.002). With the progression of puberty, negative associations between BMI and SHBG disappeared while FSH became positively associated with HOMA-IR (beta = 0.678, p = 0.025) and fasting insulin (beta = 0.668, p = 0.027). Conclusions Higher serum FSH levels in prepubertal children were associated with an increased risk of MetS development during pubertal transition. Along with nonlinear associations between varying serum FSH levels and IR markers, our results might imply a relationship between FSH and IR of puberty.
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| 13. |
- Bergqvist, Ewa, 1971-
(author)
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Mathematics and mathematics education - two sides of the same coin : creative reasoning in university exams in mathematics
- 2006
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Doctoral thesis (other academic/artistic)abstract
- Avhandlingen består av två ganska olika delar som ändå har en del gemensamt. Del A är baserad på två artiklar i matematik och del B är baserad på två matematikdidaktiska artiklar. De matematiska artiklarna utgår från ett begrepp som heter polynomkonvexitet. Grundidén är att man skulle kunna se vissa ytor som en sorts ”tak” (tänk på taket till en carport). Alla punkter, eller positioner, ”under taket” (ungefär som de platser som skyddas från regn av carporttaket) ligger i något som kallas ”polynomkonvexa höljet.” Tidigare forskning har visat att för ett givet tak och en given punkt så finns det ett sätt att avgöra om punkten ligger ”under taket”. Det finns nämligen i så fall alltid en sorts matematisk funktion med vissa egenskaper. Finns det ingen sådan funktion så ligger inte punkten under taket och tvärt om; ligger punkten utanför taket så finns det heller ingen sådan funktion. Jag visar i min första artikel att det kan finnas flera olika sådana funktioner till en punkt som ligger under taket. I den andra artikeln visar jag några exempel på hur man kan konstruera sådana funktioner när man vet hur taket ser ut och var under taket punkten ligger. De matematikdidaktiska artiklarna i avhandlingen handlar om vad som krävs av studenterna när de gör universitetstentor i matematik. Vissa uppgifter kan gå att lösa genom att studenterna lär sig någonting utantill ur läroboken och sen skriver ner det på tentan. Andra går kanske att lösa med hjälp en algoritm, ett ”recept,” som studenterna har övat på att använda. Båda dessa sätt att resonera kallas imitativt resonemang. Om uppgiften kräver att studenterna ”tänker själva” och skapar en (för dem) ny lösning, så kallas det kreativt resonemang. Forskning visar att elever i stor utsträckning väljer att jobba med imitativt resonemang, även när uppgifterna inte går att lösa på det sättet. Mycket pekar också på att de svårigheter med att lära sig matematik som elever ofta har är nära kopplat till detta arbetssätt. Det är därför viktigt att undersöka i vilken utsträckning de möter olika typer av resonemang i undervisningen. Den första artikeln består av en genomgång av tentauppgifter där det noggrant avgörs vilken typ av resonemang som de kräver av studenterna. Resultatet visar att studenterna kunde bli godkända på nästan alla tentorna med hjälp av imitativt resonemang. Den andra artikeln baserades på intervjuer med sex av de lärare som konstruerat tentorna. Syftet var att ta reda på varför tentorna såg ut som de gjorde och varför det räckte med imitativt resonemang för att klara dem. Det visade sig att lärarna kopplade uppgifternas svårighetsgrad till resonemangstypen. De ansåg att om uppgiften krävde kreativt resonemang så var den svår och att de uppgifter som gick att lösa med imitativt resonemang var lättare. Lärarna menade att under rådande omständigheter, t.ex. studenternas försämrade förkunskaper, så är det inte rimligt att kräva mer kreativt resonemang vid tentamenstillfället.
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| 14. |
- Bergsten, Christer, 1949-, et al.
(author)
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Preparing pre-service mathematics teachers for STEM education : an analysis of lesson proposals
- 2019
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In: ZDM - the International Journal on Mathematics Education. - : Springer. - 1863-9690 .- 1863-9704. ; 51:6, s. 941-953
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Journal article (peer-reviewed)abstract
- Based on an investigation of research literature on the role of mathematics within the context of STEM education and twenty-first century skills, this explorative study presents and analyses 19 pre-service teachers’ lesson proposals for innovative STEM activities in secondary mathematics classrooms. Drawing on a categorisation of twenty-first century skills and key concepts from Realistic Mathematics Education and Basil Bernstein’s writings, the analysis indicated a use of detailed instructions regarding what students should do but unspecified criteria for their expected knowledge productions. Rather than serving as a digital tool for problem solving, programming was used for the purpose of generalising students’ conceptual knowledge in mathematics. At the same time a focus on modelling and applications in the STEM activities tended to weaken the disciplinary character of mathematics. The learning of various twenty-first century skills was promoted to different extents. The study raises a discussion of affordances and constraints regarding students’ access to mathematical knowledge through different modes of integration of mathematics and other STEM subjects aiming to support the development of twenty-first century skills.
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| 15. |
- Bergsten, Eva L., 1969-, et al.
(author)
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Hälsoeffekter och förebyggande arbete vid vibrationsexponering i saneringsföretag
- 2013
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Reports (other academic/artistic)abstract
- Den övergripande målsättningen med projektet var att få en ökad kunskap om hur saneringsföretag i Uppsala, Gävleborgs och Dalarnas län arbetar för att förebygga negativa hälsoeffekter av exponering av hand- arm vibrationer. Syftet med studien var att undersöka kunskapsläget angående risker med arbete med vibrerande verktyg, samarbetet med företagshälsovården och genomförande av medicinska kontroller hos saneringsföretag i regionen. Strukturerade telefonintervjuer med 15 saneringsföretag genomfördes. Ett samarbete med ett större saneringsföretag inleddes och medicinska undersökningar genomfördes på deras anställda av ergonom ute på arbetsplatsen. Aktiviteterna i projektet inspirerade företaget att själva initiera riskbedömningar och vibrationsmätningar som en start på ett eget förbättringsarbete. Intervjuerna visade att kunskapsläget i företagen angående regelverk och arbete med vibrerande verktyg var dåligt och trots att de flesta hade företagshälsovård så uttalades ett missnöje gentemot företagshälsovården angående stöd och information i dessa frågor. Bristfällig kunskap och svårigheter att tolka regelverket kan ligga bakom att det brister vad gäller riskbedömningar och lagstadgade medicinska kontroller i saneringsföretagen. Besvärsfrekvenserna i nacke och övre extremiteter hos sanerarna i det undersökta företaget var höga och det fanns också personer med tidiga tecken på kärl- och nervskador. Resultatet av det här projektet är ett litet komplement till den kunskap som redan finns på området men visar att det finns all anledning att lägga resurser på ett förebyggande arbete för den här yrkesgruppen som tidigare inte studerats i någon större utsträckning. Det finns ett outtalat behov av informations- och utbildningsinsatser på området som till stor del beror på okunskap hos företagen men kanske också hos företagshälsovården eftersom deras insatser ser ut att ha varit begränsade. En viktig följd av projektet var att det undersökta företaget på eget initiativ men med stöd av projektet initierade en arbetsgrupp och ett förebyggande arbete för att minska exponeringen för vibrationer. Detta arbete inkluderade riktlinjer för riskbedömningar och vibrationsmätningar av verktyg samt utbildning av ledning och personal. Projektets upplägg och innehåll lämpar sig således väl för att följas av företagshälsovård i deras arbete med att stötta sina kundföretag
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| 16. |
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| 17. |
- Bergsten, Linnea, et al.
(author)
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Designing engaging computer based simulation games for increasing societal resilience to payment system
- 2020
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In: Proceedings of the 2020 the 3rd International Conference on Computers in Management and Business (ICCMB 2020) Session - Computer and Mobile Technology. - New York : Association for Computing Machinery (ACM). - 9781450376778 ; , s. 166-172, s. 166-172
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Conference paper (peer-reviewed)abstract
- Large or lengthy disruptions to the card payment system are threats that can cause crisis in society, especially in countries where other payment options are scarce. This paper presents a study that provides suggestions on how to improve a simulation game used to increase societal resilience to payment system disruptions. Questionnaires and interviews have been used to investigate how 16 participant in crisis exercises experience realism, relevance and validity in such exercises. Suggestions on how to improve the simulation game are provided, such as improvements to the graphical interface and introducing supporting roles from the exercise management.
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| 18. |
- Bergsten, Lisa, 1990-
(author)
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Housing tenures in Sweden; from rental to ownership and intermediate tenures
- 2023
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Licentiate thesis (other academic/artistic)abstract
- The importance of housing tenures for a well-functioning housing market is repeatedly emphasized. Such suggestions include the need for balance between tenures, various tenures, mixed tenures in neighborhoods, et cetera. The development of new types of housing tenures has also been noticed as a tool or vehicle to make the housing market accessible to more people, either through creating more affordable housing or supporting homeownership. Since these tenures often combine attributes from both ownership and rental - and place somewhere in between rental and ownership on a continuum, they are often described as intermediate housing tenures. Intermediate tenures and concepts have been developed in Sweden as more people encounter difficulties accessing the housing market.As these new tenures and schemes develop, so does the need to increase the understanding of them, for example, in terms of the legal framework, rights, obligations, as well as risk exposure. This thesis examines the content of various tenures (established and new ones) and explores how and why intermediate tenures and concepts have been developed. This thesis includes two appended papers. The first paper is a comparative case study examining the design and content of the primary tenures in four Nordic countries. The second paper is a case study of four intermediate concepts in Sweden. As methods for data collection, document and literature studies were used for both papers, and paper 2 was supplemented with expert interviews with representatives from the concept developers.The findings imply significant similarities between the tenures in the four Nordic countries based on their design and content. Based on the literature, some attributes for overall tenures, such as ownership and rental, can be pointed out (although major differences still exist between tenure forms). In summary, attributes associated with ownership include far-reaching rights and responsibilities as well as risk-taking. In comparison, these rights are much more restricted for rentals, which do not include risk- taking. This also corresponds with the findings, showing that tenures within ownership have the most far- reaching rights, particularly regarding the right to transfer or let out the housing unit and the value therefrom. Furthermore, the rights are most restricted for rentals, while the tenures between ownership and rental also have bundles of rights in between. The studied intermediate tenures and concepts in Sweden were described to have evolved from the difficulties many faces in accessing the housing market (or the poor housing conditions that prevailed when they were created), like intermediate tenures in countries worldwide. Most of the studied concepts are new and, thus, still in the establishment phase. However, the developers see potential to scale up the concepts. Challenges identified in order to establish and scale up such concepts are to reach out with information to various actors and to achieve a certain degree of recognition, getting access to buildable land, and financial issues. The financial issues both concern the financial ability to initiate this type of project and to consider the current members' interest while scaling up the concepts.This thesis has contributed to the literature on intermediate housing tenures by providing examples of four cases of intermediate tenures from a Swedish context. This contribution can provide insights into the development of such tenures and concepts as well as some of the challenges the developers have met. These insights can also be a valuable practical contribution for actors, such as municipalities, policymakers, housing developers, and so forth, to understand some of the difficulties developers of new concepts meet.
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| 19. |
- Bergsten, Peter, et al.
(author)
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Appearance of glucose-induced insulin release in fetal rat β-cells
- 1998
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In: Journal of Endocrinology. - : Society for Endocrinology. - 0022-0795 .- 1479-6805. ; 158:1, s. 115-120
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Journal article (peer-reviewed)abstract
- Fetal rat pancreatic cells were isolated from pancreatic primordia on days 12-14 of pregnancy and cultured for 48 h in the presence of 5 mmol/l glucose. Insulin accumulation in the medium over the next 24 h was measured. Cultured cells from day 12 fetuses secreted about 1 fmol insulin per pancreas in response to 5 or 15 mmol/l glucose irrespective of whether 1 mmol/l tolbutamide, 400 mumol/l diazoxide, 5 mmol/l theophylline or 10 mmol/l mannoheptulose was present. In contrast, insulin released from day 13 cultured cells increased significantly from 3.0 +/- 0.6 to 6.2 +/- 2.2 fmol per pancreas, when the glucose concentration was raised. Tolbutamide increased, diazoxide and mannoheptulose decreased and theophylline had no effect on insulin release. Even more pronounced effects were found on insulin release from day 14 cultured cells, in which theophylline also increased the release. In addition, insulin release from cells from pregnancy day 14 was 75 +/- 16 amol/min per pancreas when the cells were perifused for 15-20 min in the presence of 5 mmol/l glucose within 3 h of isolation. Increasing the glucose concentration to 15 mmol/l or adding tolbutamide increased, whereas diazoxide decreased, insulin release in the freshly isolated cells. The insulin content of rat pancreata from pregnancy day 13 was 0.06 +/- 0.01 pmol per pancreas and increased approximately 10-fold every second day up to 6.7 +/- 0.9 pmol on day 17 of pregnancy. Between day 17 and 19 the pancreatic insulin content increased about fivefold to 39 +/- 2 pmol. The present data suggest that critical components of the insulin-secretory machinery, including ATP-regulated K+ channels, glucokinase and adenylate cyclase activities, are present in the developing beta-cell earlier than hitherto thought.
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| 21. |
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| 22. |
- Bergsten, Peter, et al.
(author)
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Miljöförbättrande åtgärder i Mörrumsån och Ångermanälven, med fokus på havsvandrande arter
- 2014
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Reports (other academic/artistic)abstract
- Föreliggande rapports syfte är att sammanställa resultaten från en utredning av förutsättningar för miljöförbättrande åtgärder i de utbyggda vattendragen Ångermanälven och Mörrumsån. Förutsättningar för de geografiska områdena är sammanställda och effekter av möjliga åtgärder har analyserats; dels hydrauliska flödessimuleringar, dels en populationsmodell för laxfisk. Fokus har lagts på åtgärder för havsvandrande fisk.ÅngermanälvenÅngermanälven är Sveriges tredje största älv i fråga om vattenföring, med en medelvattenföring på knappt 500 m3/s. Det finns ett fyrtiotal större vattenkraftverk, samt ett antal mindre, fördelade i de tre huvudgrenarna Åsele-, Fax- och Fjällsjöälven. Studien omfattar nedre delarna av Åseleälven (upp till Nämforsen) och Faxälven (upp till Storfinnforsen). Bland de inom uppdraget aktuella kraftverken finns gamla åfåror i anslutning till de fyra stationerna i Faxälven, Hjälta, Forsse, Edsele och Ramsele.Idag når havsvandrande arter upp till Sollefteå kraftverk, ca 3 mil uppströms mynningen. Lax och havsöring fiskas enbart nedströms Sollefteå kraftverk, och utsättningar görs från två kompensationsodlingar, vid Forsmo och strax nedströms Hjälta.Resultaten för Ångermanälven visar på en potential för att etablera ett svagt men livskraftigt laxbestånd uppströms Sollefteå kraftverk. Förutsättningarna utgörs av en kombination av åtgärder, fiskväg vid Sollefteå samt minimitappning av ca 8 m3/s vid Hjälta kraftstation. Detta skulle enligt modellförsök resultera i ett bestånd av i medeltal ca 150 återvändande laxar per år, med en uppskattad kostnad på ca 26 MSEK/år (exklusive kostnad för fiskvandringsväg vid Sollefteå), p.g.a. produktionsbortfall.Möjligheterna för åtgärder riktade mot havsvandrande fisk längre upp i Faxälven är mycket små. Mindre arealer potentiella reproduktionsområden, i kombination med dödlighet vid passage av kraftverk, gör att bara några 10-tal honor tar sig upp per år. Ramsele gamla fåra skulle kunna erbjuda förhållandevis stora reproduktionsområden, men en nödvändig passage av fyra kraftverk gör det mycket svårt att tillgängliggöra sträckan, även om fiskvägar installeras.MörrumsånMörrumsån mynnar i Pukavikbukten vid Mörrum, och har en medelvattenföring på knappt 30 m3/s. Inom hela systemet Mörrumsån finns 24 vattenkraftverk, varav de sju som omfattas av denna utredning ligger belägna i den nedre delen av ån, nedströms sjön Åsnen. Genom denna avgränsning omfattar studien samtliga E.ONs anläggningar i Mörrumsån. Av de aktuella kraftverken finns gamla åfåror i anslutning till Granö, Hemsjö övre, Hemsjö nedre samt Fridafors nedre.Mörrumsån anses utgöra södra Sveriges viktigaste laxälv och idag når havsvandrande fisk upp till Fridafors nedre, ca 3 mil från mynningen. Fiskvägar finns installerade vid de tre nedströms kraftstationerna, Marieberg och Hemsjö nedre och övre. Utsättningar av smolt och yngel från havsöring sker årligen i de nedre delarna av ån, smolt i Kungsforsen vid Mörrum, och yngel i flera av de tillrinnande bäckarna.Med utgångspunkt i potentiella reproduktionsområden i Granö gamla fåra har möjligheten att etablera lax- och öringbestånd uppströms Fridafors studerats. Åtgärderna utgörs av fiskvägar i Fridafors samt minimitappning i Granö, ev. i kombination med biotopvårdsåtgärder. Resultaten visar att för att uppnå ett livskraftigt bestånd uppströms Fridafors ställs höga krav på funktion av de fem fiskvägarna. Om ett antagande görs att 95% av smolten passerar varje station tack vare spill under utvandringsperioden, måste uppströmspassage ske med en genomsnittlig effektivitet av 90% per station. Vid 80% klarar bara ett par tiotal honor sig upp till fåran för lek, medan populationen balanserar på gränsen till livskraftighet vid 90%. Eftersom det är så många fiskvägar får passagerna stort utslag på överlevnaden, och det ger t.ex. större effekt att öka fiskvägarnas effektivitet från 80 till 90% jämfört med att dubblera mängden reproduktionsområdena från 3,5 till 7 ha . Att maximera den gamla fårans potential genom biotopvårdsåtgärder är relevant, men bör därför ha lägre prioritet jämfört med att säkerställa fiskvägarnas funktion.Den föreslagna minimitappningen i Granö på 2,3 m3/s baseras på resultaten från flödessimuleringarna för att på ett kostnadseffektivt sätt nå goda förhållanden för reproduktion i fåran. Den totala årliga kostnaden uppskattas till ca 2 MSEK, om flödet ökas till 9,5 m3/s ger det ett ca 4 gånger så stort produktionsbortfall, medan den ekologiska effekten endast ökar med ca 10 %.En tänkbar åtgärd för att uppnå en positiv effekt på laxfisk i Mörrumsån vore en utrivning av Mariebergs kraftstation, en åtgärd som enligt modellen har potential att fördubbla laxbeståndet uppströms Marieberg. En utrivning av Marieberg skulle, utöver kostnader för återställning och utrivning, innebära ett produktionsbortfall bestående av hela kraftstationens kapacitet (3,2 GWh), motsvarande ca 1 MSEK per år (inräknad nuvarande kostnader för drift och underhåll, men exklusive utrivningskostnader).Frånsett utrivning är potentialen ur ett ekologiskt perspektiv, räknat i antal återvändande laxfisk, likvärdig i Ångermanälven, med en fiskväg i Sollefteå kombinerat med minimitappning i Hjälta, jämfört med Granö i Mörrumsån. Ur ett kostnadsperspektiv vore det ca 4 gånger så dyrt (ca 26 MSEK/år exklusive fiskväg i Sollefteå) som att genomföra åtgärderna vid Fridafors/Granö. Skillnaden ligger bland annat i att i Mörrumsån innebär studerade åtgärder ett tillskott till en befintlig population i vattendraget, medan det i Ångermanälven idag inte finns ett bestånd med naturlig reproduktion.Utifrån den samhällsekonomiska analysen ger ingen åtgärd med minimitappningar och/eller fiskvägar ett positivt resultat. Beroende på vilka scenarier som används blir den samhällsekonomiska förlusten av åtgärder i Granö från 10 MSEK och uppåt (nuvärde), medan förlusten i Ångermanälven blir drygt 200 MSEK och uppåt.
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| 23. |
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| 24. |
- Cadamuro, Janne, et al.
(author)
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Deviating glucose results in an international dual-center study. A root cause investigation
- 2022
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In: Biochemia Medica. - : Croatian Society for Medical Biochemistry and Laboratory Medicine. - 1330-0962 .- 1846-7482. ; 32:1
-
Journal article (peer-reviewed)abstract
- During a dual-center study on obese and normal weight children and adolescents, focusing on glucose metabolism, we observed a marked difference in glucose results (N = 16,840) between the two sites, Salzburg, Austria and Uppsala, Sweden (P < 0.001). After excluding differences in patient characteristics between the two populations as cause of this finding, we investigated other preanalytic influences. Finally, only the tubes used for blood collection at the two sites were left to evaluate. While the Vacuette FC-Mix tube (Greiner Bio-One, Kremsmunster, Austria) was used in Uppsala, in Salzburg blood collections were performed with a lithium heparin tube (LH-Monovette, Sarstedt, Germany). To prove our hypothesis, we collected two blood samples in either of these tubes from 51 children (Salzburg N = 27, Uppsala N = 24) and compared the measured glucose results. Indeed, we found the suspected bias and calculated a correction formula, which significantly diminished the differences of glucose results between the two sites (P = 0.023). Our finding is in line with those of other studies and although this issue should be widely known, we feel that it is widely neglected, especially when comparing glucose concentrations across Europe, using large databases without any information on preanalytic sample handling.
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| 25. |
- Cen, Jing, et al.
(author)
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Fatty acids stimulate insulin secretion from human pancreatic islets at fasting glucose concentrations via mitochondria-dependent and -independent mechanisms
- 2016
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In: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 13
-
Journal article (peer-reviewed)abstract
- Background: Free fatty acids (FFAs) acutely stimulate insulin secretion from pancreatic islets. Conflicting results have been presented regarding this effect at non-stimulatory glucose concentration, however. The aim of our study was to investigate how long-chain FFAs affect insulin secretion from isolated human pancreatic islets in the presence of physiologically fasting glucose concentrations and to explore the contribution of mitochondria to the effects on secretion. Methods: Insulin secretion from human pancreatic islets was measured from short-term static incubation or perfusion system at fasting glucose concentration (5.5 mM) with or without 4 different FFAs (palmitate, palmitoleate, stearate, and oleate). The contribution of mitochondrial metabolism to the effects of fatty acid-stimulated insulin secretion was explored. Results: The average increase in insulin secretion, measured from statically incubated and dynamically perifused human islets, was about 2-fold for saturated free fatty acids (SFAs) (palmitate and stearate) and 3-fold for mono-unsaturated free fatty acids (MUFAs) (palmitoleate and oleate) compared with 5.5 mmol/l glucose alone. Accordingly, MUFAs induced 50 % and SFAs 20 % higher levels of oxygen consumption compared with islets exposed to 5.5 mmol/l glucose alone. The effect was due to increased glycolysis. When glucose was omitted from the medium, addition of the FFAs did not affect oxygen consumption. However, the FFAs still stimulated insulin secretion from the islets although secretion was more than halved. The mitochondria-independent action was via fatty acid metabolism and FFAR1/GPR40 signaling. Conclusions: The findings suggest that long-chain FFAs acutely induce insulin secretion from human islets at physiologically fasting glucose concentrations, with MUFAs being more potent than SFAs, and that this effect is associated with increased glycolytic flux and mitochondrial respiration.
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| 26. |
- Cen, Jing, 1985-
(author)
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Free fatty acids and insulin hypersecretion studied in human islets
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- Free fatty acid (FFA) levels are increased in many obese subjects. High FFA levels stimulate the pancreatic beta-cells but have negative long-term effects. In obese children with high FFA levels circulating insulin concentration is high early in life but decline with age precipitating the development of type 2 diabetes mellitus (T2DM). The present study aims at preventing this development of T2DM by defining underlying mechanisms of insulin hypersecretion. Such mechanisms will be identified by studying regulation of insulin secretion from human pancreatic islets and human EndoC-βH1 cells exposed to elevated FFA levels.We found that elevated concentrations of FFAs acutely stimulate insulin from human pancreatic islets at fasting blood glucose level, with mono-unsatured being more potent than saturated fatty acids. Enhanced secretion was associated with increased glycolytic flux and mitochondrial respiration. Continued exposure to elevated palmitate levels for up to 2 days accentuated insulin secretion, whereas 7 days’ exposure caused secretory decline. Metformin prevented insulin hypersecretion from human islets treated with palmitate for 2 days by decreasing mitochondrial metabolism. In islets exposed to palmitate for 7 days metformin improved insulin secretion by enhancing calcium binding protein sorcin levels and thereby reducing ER stress and apoptosis. Downregulation of sorcin had negative effects on insulin secretion, mitochondrial metabolism and ER stress in human islets and EndoC-βH1 cells. Specific cellular pathways involved in insulin hypersecretion and secretory decline were identified by microarray expression analysis and subsequent bioinformatics in human islets cultured with palmitate for 0, 4, 12 hours, 1, 2, and 7 days.In conclusion, beta-cells respond to elevated levels of FFAs by initially augmenting insulin release followed by declining secretory levels after prolonged exposure. Metformin normalizes these secretory aberrations. Specific signaling pathways and proteins including sorcin contribute to the secretory alterations induced by palmitate. When developing strategies for prevention of T2DM in obese children with elevated FFA levels, metformin should be considered as well as novel strategies involving sorcin and the identified specific pathways.
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| 27. |
- Cen, Jing, et al.
(author)
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Mechanisms of beneficial effects of metformin on fatty acid-treated human islets
- 2018
-
In: Journal of Molecular Endocrinology. - 0952-5041 .- 1479-6813. ; 61:3, s. 91-99
-
Journal article (peer-reviewed)abstract
- Elevated levels of palmitate accentuate glucose-stimulated insulin secretion (GSIS) after short-term and cause beta-cell dysfunction after prolonged exposure. We investigated whether metformin, the first-line oral drug for treatment of T2DM, has beneficial effects on FFA-treated human islets and the potential mechanisms behind the effects. Insulin secretion, oxygen consumption rate (OCR), AMPK activation, endoplasmic reticulum (ER) stress and apoptosis were examined in isolated human islets after exposure to elevated levels of palmitate in the absence or presence of metformin. Palmitate exposure doubled GSIS after 2 days but halved after 7 days compared with control. Inclusion of metformin during palmitate exposure normalized insulin secretion both after 2 and 7 days. After 2-day exposure to palmitate, OCR and the marker of the adaptive arm of ER stress response (sorcin) were significantly raised, whereas AMPK phosphorylation, markers of pro-apoptotic arm of ER stress response (p-EIF2α and CHOP) and apoptosis (cleaved caspase 3) were not affected. Presence of metformin during 2-day palmitate exposure normalized OCR and sorcin levels. After 7-day exposure to palmitate, OCR and sorcin were not significantly different from control level, p-AMPK was reduced and p-EIF2α, CHOP and cleaved caspase 3 were strongly upregulated. Presence of metformin during 7-day culture with palmitate normalized the level of p-AMPK, p-EIF2α, CHOP and cleaved caspase 3 but significantly increased the level of sorcin. Our study demonstrates that metformin prevents early insulin hypersecretion and later decrease in insulin secretion from palmitate-treated human islets by utilizing different mechanisms.
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| 28. |
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| 29. |
- Cen, Jing, et al.
(author)
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Sorcin counteracts lipotoxicity in palmitate-exposed human beta-cells
-
Other publication (other academic/artistic)abstract
- In obese subjects elevated circulating levels of free fatty acids (FFAs) have been connected with hyperinsulinemia and development of type 2 diabetes. In human islets insulin secretion is accentuated when palmitate concentration is increased for short time periods. Our previous findings indicated that increased sorcin expression may delay development of ER stress in such human islets exposed to palmitate. In the present study we tested this hypothesis by using human islets and human EndoC-βH1 cells transfected with lenti-viral transduction particles of anti-sorcin. Human islets and EndoC-βH1 cells treated with palmitate for 2 days induced sorcin expression. The beta-cells showed enhanced glucose-stimulated insulin secretion (GSIS), mitochondrial respiration and glycolysis and no alterations in ER stress and apoptosis. When sorcin was knocked down, palmitate-induced upregulation of sorcin was reduced. The beta-cells showed reduced GSIS, mitochondrial respiration and glycolysis and increased ER stress and apoptosis. We conclude that enhanced sorcin levels play a role in preventing lipotoxicity in beta-cells exposed to elevated palmitate levels for prolonged time periods.
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| 30. |
- Censin, J. C., et al.
(author)
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Childhood adiposity and risk of type 1 diabetes : A Mendelian randomization study
- 2017
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:8
-
Journal article (peer-reviewed)abstract
- Background The incidence of type 1 diabetes (T1D) is increasing globally. One hypothesis is that increasing childhood obesity rates may explain part of this increase, but, as T1D is rare, intervention studies are challenging to perform. The aim of this study was to assess this hypothesis with a Mendelian randomization approach that uses genetic variants as instrumental variables to test for causal associations. Methods and findings We created a genetic instrument of 23 single nucleotide polymorphisms (SNPs) associated with childhood adiposity in children aged 2-10 years. Summary-level association results for these 23 SNPs with childhood-onset (<17 years) T1D were extracted from a meta-analysis of genome-wide association study with 5,913 T1D cases and 8,828 reference samples. Using inverse-variance weighted Mendelian randomization analysis, we found support for an effect of childhood adiposity on T1D risk (odds ratio 1.32, 95% CI 1.06-1.64 per standard deviation score in body mass index [SDS-BMI]). A sensitivity analysis provided evidence of horizontal pleiotropy bias (p = 0.04) diluting the estimates towards the null. We therefore applied Egger regression and multivariable Mendelian randomization methods to control for this type of bias and found evidence in support of a role of childhood adiposity in T1D (odds ratio in Egger regression, 2.76, 95% CI 1.40-5.44). Limitations of our study include that underlying genes and their mechanisms for most of the genetic variants included in the score are not known. Mendelian randomization requires large sample sizes, and power was limited to provide precise estimates. This research has been conducted using data from the Early Growth Genetics (EGG) Consortium, the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, the Tobacco and Genetics (TAG) Consortium, and the Social Science Genetic Association Consortium (SSGAC), as well as meta-analysis results from a T1D genome-wide association study. Conclusions This study provides genetic support for a link between childhood adiposity and T1D risk. Together with evidence from observational studies, our findings further emphasize the importance of measures to reduce the global epidemic of childhood obesity and encourage mechanistic studies.
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| 31. |
- Chowdhury, Azazul Islam, et al.
(author)
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Functional differences between aggregated and dispersed insulin-producing cells
- 2013
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:7, s. 1557-1568
-
Journal article (peer-reviewed)abstract
- Beta cells situated in the islet of Langerhans respond more vigorously to glucose than do dissociated beta cells. Mechanisms for this discrepancy were studied by comparing insulin-producing MIN6 cells aggregated into pseudoislets with MIN6 monolayer cells and mouse and human islets. MIN6 monolayers, pseudoislets and mouse and human islets were exposed to glucose, alpha-ketoisocaproic acid (KIC), pyruvate, KIC plus glutamine and the phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 or wortmannin. Insulin secretion (ELISA), cytoplasmic Ca2+ concentration ([Ca2+](c); microfluorometry), glucose oxidation (radiolabelling), the expression of genes involved in mitochondrial metabolism (PCR) and the phosphorylation of insulin receptor signalling proteins (western blotting) were measured. Insulin secretory responses to glucose, pyruvate, KIC and glutamine were higher in pseudoislets than monolayers and comparable to those of human islets. Glucose oxidation and genes for mitochondrial metabolism were upregulated in pseudoislets compared with single cells and monolayers, respectively. Phosphorylation at the inhibitory S636/639 site of IRS-1 was significantly higher in monolayers and dispersed human and mouse cells than pseudoislets and intact human and mouse islets. PI3K inhibition only slightly attenuated glucose-stimulated insulin secretion from monolayers, but substantially reduced that from pseudoislets and human and mouse islets without suppressing the glucose-induced [Ca2+](c) response. We propose that islet architecture is critical for proper beta cell mitochondrial metabolism and IRS-1 signalling, and that PI3K regulates insulin secretion at a step distal to the elevation of [Ca2+](c).
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| 32. |
- Chowdhury, Azazul Islam, et al.
(author)
-
GLP-1 analogue recovers impaired insulin secretion from human islets treated with palmitate via down-regulation of SOCS2
- 2017
-
In: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 439:C, s. 194-202
-
Journal article (peer-reviewed)abstract
- Elevated circulating palmitate levels have been connected with type 2 diabetes mellitus. GLP-1 has favorable effects on beta-cells function. The aim was to identify mechanisms for decreased GSIS after long-term palmitate exposure and restoration by GLP-1 by analyzing changes in G-protein coupled receptor (GPCR) pathway signaling. Insulin secretory response to 20 mM glucose was attenuated after 7 days in islets exposed to palmitate but inclusion of exendin-4 restored secretion. Palmitate treatment altered genes of several GPCR signaling pathways including inflammatory pathways with up-regulated IL-1B, SOCS1 and SOCS2 transcript levels. Protein level of SOCS2 was also up-regulated by palmitate and accompanied by down-regulation of pAkt(T308), which was restored by exendin-4 treatment. When SOCS2 was knocked down, palmitate-induced clown-regulation of IRS-1 and pAkt(T308) was prevented and GSIS, proinsulin to insulin ratio and apoptosis was restored. Long-term palmitate treatment up regulates SOCS2 and reduces PI3K activity, thereby impairing GSIS. GLP-1 reverts the palmitate-induced effects.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Chowdhury, Azazul, et al.
(author)
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Signaling in Insulin-Secreting MIN6 Pseudoislets and Monolayer Cells
- 2013
-
In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:12, s. 5954-5962
-
Journal article (peer-reviewed)abstract
- Cell cell interactions are of fundamental importance for cellular function. In islets of Langerhans, which control blood glucose levels by secreting insulin in response to the blood . glucose concentration, the secretory response of intact islets is c higher than that of insulin-producing beta-cells not arranged in the islet architecture. The objective was to define mechanisms by which cellular performance is enhanced when cells are arranged in a) three-dimensional space. The task was addressed by making a c comprehensive analysis based on protein expression patterns " generated from insulin-secreting MIN6 cells grown as islet-like c clusters, so-called pseudoislets, and in monolayers. After culture, glucose-stimulated insulin secretion (GSIS) was measured from monolayers and pseudoislets. GSIS rose 6-fold in pseudoislets but only 3-fold in monolayers when the glucose concentration was increased from 2 to 20 mmol/L. Proteins from pseudoislets and monolayers were extracted and analyzed by liquid-chromatography mass spectrometry, and differentially expressed proteins were mapped onto KEGG pathways. Protein profiling identified 1576 proteins, which were common to pseudoislets and monolayers. When mapped onto KEGG pathways, 11 highly enriched pathways were identified. On the basis of differences in expression of proteins belonging to the pathways in pseudoislets and monolayers, predictions of differential pathway activation were performed. Mechanisms enhancing insulin secretory capacity of the beta-cell, when situated in the islet, include pathways regulating glucose metabolism, cell interaction, and translational regulation.
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| 37. |
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| 38. |
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| 39. |
- Ciba, Iris, et al.
(author)
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Prevalence of different states of glucose intolerance in Sri Lankan children and adolescents with obesity and its relation to other comorbidities.
- 2021
-
In: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 22:2, s. 168-181
-
Journal article (peer-reviewed)abstract
- BACKGROUND: South Asian adults have higher prevalence of obesity comorbidities than other ethnic groups. Whether this also is true for Sri Lankan children with obesity has rarely been investigated.OBJECTIVE: To investigate prevalence of glucose intolerance and other comorbidities in Sri Lankan children with obesity and compare them with Swedish children. To identify risk factors associated with glucose intolerance.SUBJECTS: A total of 357 Sri Lankan children (185 boys), aged 7 to 17 years with BMI-SDS ≥2.0 from a cross-sectional school screening in Negombo. A total of 167 subjects from this study population were matched for sex, BMI-SDS and age with 167 Swedish subjects from the ULSCO cohort for comparison.METHODS: After a 12 hour overnight fast, blood samples were collected and oral glucose tolerance test was performed. Body fat mass was assessed by bioelectrical impedance assay. Data regarding medical history and socioeconomic status were obtained from questionnaires.RESULTS: Based on levels of fasting glucose (FG) and 2 hours-glucose (2 hours-G), Sri Lankan subjects were divided into five groups: normal glucose tolerance (77.5%, n = 276), isolated impaired fasting glucose according to ADA criteria (9.0%, n = 32), isolated impaired glucose tolerance (8.4%, n = 30), combined impaired fasting glucose (IFG) + impaired glucose tolerance (IGT) (3.1%, n = 11) and type 2 diabetes mellitus (2.0%, n = 7). FG, 2 hours-insulin and educational status of the father independently increased the Odds ratio to have elevated 2 hours-G. Sri Lankan subjects had higher percentage of body fat, but less abdominal fat than Swedish subjects.CONCLUSION: High prevalence in Sri Lankan children with obesity shows that screening for glucose intolerance is important even if asymptomatic.
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| 40. |
- Ciba, Iris, et al.
(author)
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Studies in children with obesity in two European treatment centres show a high prevalence of impaired glucose metabolism in the Swedish cohort
- 2024
-
In: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 113:2, s. 286-295
-
Journal article (peer-reviewed)abstract
- Aim: To investigate the prevalence and possible risk factors for the development of impaired glucose metabolism in children and adolescents with obesity.Methods: This was a cross-sectional retrospective cohort study, including 634 patients with obesity and 98 normal weight controls aged 4-18 years from the Beta-cell function in Juvenile Diabetes and Obesity (Beta-JUDO) cohort, a dual-centre study at Uppsala University Hospital (Sweden) and Paracelsus Medical University Hospital (Salzburg, Austria) conducted between 2012 and 2021. A longitudinal subgroup analysis, including 188 of these subjects was performed. Impaired glucose metabolism was diagnosed by oral glucose tolerance tests according to American Diabetes Association criteria.Results: The prevalence of impaired glucose metabolism was 72% in Uppsala patients, 24% in Salzburg patients, 30% in Uppsala controls and 13% in Salzburg controls. The prevalence was lower at the follow-up visits compared with baseline both in Uppsala and Salzburg patients. A family history of type 2 diabetes showed the strongest association with impaired glucose metabolism at the follow-up visits besides belonging to the Uppsala cohort.Conclusion: The prevalence of impaired glucose metabolism was extraordinarily high in Swedish children and adolescents with obesity, but decreased during the follow-up period.
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| 41. |
- Drzazga, Anna, et al.
(author)
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Lysophosphatidylcholine and its phosphorothioate analogues potentiate insulin secretion via GPR40 (FFAR1), GPR55 and GPR119 receptors in a different manner
- 2018
-
In: Molecular and Cellular Endocrinology. - : ELSEVIER IRELAND LTD. - 0303-7207 .- 1872-8057. ; 472, s. 117-125
-
Journal article (peer-reviewed)abstract
- Lysophosphatidylcholine (LPC) is an endogenous ligand for GPR119 receptor, mediating glucose-stimulated insulin secretion (GSIS). We demonstrate that LPC facilitates GSIS in MINE pancreatic beta-cell line and murine islets of Langerhans by recognizing not only GPR119 but also GPR40 (free fatty acid receptor 1) and GPR55 activated by lysophosphatidylinositol. Natural LPCs are unstable when administered in vivo limiting their therapeutic value and therefore, we present phosphorothioate LPC analogues with increased stability. All the modified LPCs under study (12:0,14:0,16:0,18:0, and 18:1) significantly enhanced GSIS. The 16:0 sulfur analogue was the most potent, evoking 2-fold accentuated GSIS compared to the native counterpart. Interestingly, LPC analogues evoked GPR40-, GPR55-and GPR119 dependent [Ca2+](i), signaling, but did not stimulate cAMP accumulation as in the case of unmodified molecules. Thus, introduction of a phosphorothioate function not only increases LPC stability but also modulates affinity towards receptor targets and evokes different signaling pathways.
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| 42. |
- Elksnis, Andris, et al.
(author)
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Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK
- 2021
-
In: Clinical Science. - : Portland Press. - 0143-5221 .- 1470-8736. ; 135:19, s. 2243-2263
-
Journal article (peer-reviewed)abstract
- The protein tyrosine kinase inhibitor imatinib is used in the treatment of various malignancies but may also promote beneficial effects in the treatment of diabetes. The aim of the present investigation was to characterize the mechanisms by which imatinib protects insulin producing cells. Treatment of non-obese diabetic (NOD) mice with imatinib resulted in increased beta-cell AMP-activated kinase (AMPK) phosphorylation. Imatinib activated AMPK also in vitro, resulting in decreased ribosomal protein S6 phosphorylation and protection against islet amyloid polypeptide (IAPP)-aggregation, thioredoxin interacting protein (TXNIP) up-regulation and beta-cell death. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) mimicked and compound C counteracted the effect of imatinib on beta-cell survival. Imatinib-induced AMPK activation was preceded by reduced glucose/pyruvate-dependent respiration, increased glycolysis rates, and a lowered ATP/AMP ratio. Imatinib augmented the fractional oxidation of fatty acids/malate, possibly via a direct interaction with the beta-oxidation enzyme enoyl coenzyme A hydratase, short chain, 1, mitochondrial (ECHS1). In non-beta cells, imatinib reduced respiratory chain complex I and II-mediated respiration and acyl-CoA carboxylase (ACC) phosphorylation, suggesting that mitochondrial effects of imatinib are not beta-cell specific. In conclusion, tyrosine kinase inhibitors modestly inhibit mitochondrial respiration, leading to AMPK activation and TXNIP down-regulation, which in turn protects against beta-cell death.
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| 43. |
- Fazey, Ioan, et al.
(author)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Journal article (peer-reviewed)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 44. |
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| 45. |
- Forslund, Anders, et al.
(author)
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Uppsala Longitudinal Study of Childhood Obesity : Protocol Description
- 2014
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 133:2, s. E386-E393
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVE: The prevalence of childhood obesity has risen considerably on a global scale during the past decades, and the condition is associated with increased risk of morbidity. The objective is to describe the Uppsala Longitudinal Study of Childhood Obesity (ULSCO) cohort, including some baseline data, and outline addressed research areas that aim at identifying factors implicated in and contributing to development of obesity and obesity-related diseases, including type 2 diabetes. METHODS: Severely obese and lean control subjects are examined at enrollment and at subsequent annual visits by using detailed questionnaires, anthropometric measurements, indirect calorimetry, and functional tests such as oral glucose tolerance tests. Some subjects undergo additional characterization with MRI, subcutaneous fat biopsies, frequent blood sampling, and hyperglycemic clamps. Biological samples are obtained and stored in a biobank. RESULTS: Active recruitment started in 2010, and standard operating procedures have been established. A high participation rate and annual follow-ups have resulted in a cohort exceeding 200 subjects, including 45 lean controls (as of October 2013). Initial research focus has been on traits of the metabolic syndrome, hyperinsulinemia and identifying risk factors for type 2 diabetes. CONCLUSIONS: The ULSCO cohort serves as an important resource in defining and understanding factors contributing to childhood obesity and development of obesity-related diseases. Given the comprehensive characterization of the cohort, factors contributing to disease development and progression can be identified. Such factors are further evaluated for their mechanistic role and significance, and noncommunicable metabolic diseases are especially addressed and considered.
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| 46. |
- Fred, Rikard G., et al.
(author)
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Role of the AMP kinase in cytokine-induced human EndoC-beta H1 cell death
- 2015
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In: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 414:C, s. 53-63
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Journal article (peer-reviewed)abstract
- The aim of the present investigation was to delineate cytokine-induced signaling and death using the EndoC-beta H1 cells as a model for primary human beta-cells. The cytokines IL-1 beta and IFN-gamma induced a rapid and transient activation of NF-kappa B, STAT-1, ERK, JNK and eIF-2 alpha signaling. The EndoC-beta H1 cells died rapidly when exposed to IL-1 beta + IFN-gamma, and this occurred also in the presence of the actinomycin D. Inhibition of NF-kappa B and STAT-1 did not protect against cell death, nor did the cytokines activate iNOS expression. Instead, cytokines promoted a rapid decrease in EndoC-beta H1 cell respiration and ATP levels, and we observed protection by the AMPK activator AICAR against cytokine-induced cell death. It is concluded that EndoC-beta H1 cell death can be prevented by AMPK activation, which suggests a role for ATP depletion in cytokine-induced human beta-cell death.
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| 47. |
- Frejd, Peter, 1973-, et al.
(author)
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Mathematical modelling as a professional task
- 2016
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In: Educational Studies in Mathematics. - : Springer. - 0013-1954 .- 1573-0816. ; 91:1, s. 11-35
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Journal article (peer-reviewed)abstract
- Educational research literature on mathematical modelling is extensive. However, not much attention has been paid to empirical investigations of its scholarly knowledge from the perspective of didactic transposition processes. This paper reports from an interview study of mathematical modelling activities involving nine professional model constructors. The research question was: How can mathematical modelling by professional mathematical model constructors be characterised? The analysis of our interview data inspired by the coding procedure of grounded theory led us to the description of three main types of modelling activities as a characterisation of mathematical modelling as a professional task. In data-generated modelling the models are developed principally from quantitative data drawing on no or only some assumed knowledge of the system being modelled, while in theory-generated modelling the models are developed based on established theory. In the third activity, model-generated modelling, the development of new models is based on already established models. For all types, the use of computer support and communication between clients, constructors and other experts are central aspects. Finally, the three types of modelling activities are related to existing theoretical descriptions of mathematical modelling and the relevance of the study for mathematical modelling in education is discussed.
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| 48. |
- Frejd, Peter, 1973-, et al.
(author)
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Mathematical modelling as a professional task : Implications for education
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Other publication (other academic/artistic)abstract
- From an explorative study on how professionals engage in mathematical modelling in their work, three main types of activities were identified, i.e. empirical, theoretical and applicational modelling. Based on the outcomes of the study, some issues related to mathematical modelling in education are discussed.
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| 49. |
- Frejd, Peter
(author)
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Mathematical modelling in upper secondary school in Sweden : An exploratory investigation
- 2011
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Licentiate thesis (other academic/artistic)abstract
- The official curriculum guidelines for upper secondary school in Sweden emphasise the use of mathematical models and mathematical modelling in mathematics education. However, no explicit definitions or descriptions of the notions are given in the curriculum. This licentiate thesis is an exploratory study which investigates teachers’ and students’ conceptions of the notion of mathematical modelling as well as their attitudes and experiences of working with mathematical modelling in mathematics classrooms. One experience of mathematical modelling that faces both students and teachers which is investigated is the national course tests in mathematics. The thesis includes five papers and a preamble, where the papers are summarised, analysed, and discussed. Both quantitative and qualitative methods are being used in the thesis and theoretical aspects concerning mathematical modelling and conceptions are examined. The results indicate that mathematical modelling plays a minor role in the investigated mathematics classrooms. The students as well as the teachers were not familiar with the notion of mathematical modelling. Only 23% of the 381 students and 50 % of the 18 teachers had heard the notion before participating in the study. Both teachers and students participating in this study expressed a variety of different interpretations of the notion of mathematical modelling. Negative attitudes were expressed by the students as well as by some of the teachers concerning mathematical modelling. These negative attitudes may present obstacles for implementing mathematical modelling in the upper secondary mathematics classroom. However, these negative attitudes are related to the used test items, which may have had a negative impact on the research, especially, as the test items only test parts of the modelling process. One dominant conception found among the teachers was that mathematical modelling is related to physics or chemistry. The conclusion made from the investigation about national course tests in mathematics course D, is that there is a lack of holistic assessment of mathematical modelling. Intra-mathematical aspects of mathematical modelling are put in favour for extra-mathematical aspects. Researchers argue that if we want develop students’ modelling competency, than modelling has to be explicitly used and practised in the mathematics classrooms. However, for the Swedish upper secondary school this study concludes that this is not the case. A suggestion for future research is to focus on mathematical modelling in teacher education and design studies of incorporation of modelling activities into mathematics classrooms.
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| 50. |
- Frejd, Peter, 1973-
(author)
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Modes of Mathematical Modelling : An analysis of how modelling is used and interpreted in and out of school settings
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The relevance of using mathematics in and for out-of-school activities is one main argument for teaching mathematics in education. Mathematical modelling is considered as a bridge between the mathematics learned and taught in schools and the mathematics used at the workplace and in society and it is also a central notion in the present Swedish mathematical syllabus for upper secondary school. This doctoral thesis reports on students’, teachers’ and modelling experts’ experiences of, learning, teaching and working with mathematical modelling in and out of school settings and their interpretations of the notion of mathematical modelling.The thesis includes five papers and a preamble, where the papers are summarised, analysed, and discussed. Different methods are being used in the thesis such as video analysis of students’ collaboration working with modelling problem, interview investigations with teachers and expert modellers, content analysis of textbooks and literature review of modelling assessment. Theoretical aspects concerning mathematical modelling and the didactic transposition of modelling are examined.The results presented in this thesis provide a fragmented picture of the didactic transposition of mathematical modelling in school mathematics in Sweden. There are significant differences in how modellers, teachers and students work with modelling in different practices in terms of the goal with the modelling activity, the risks involved in using the models, the use of technology, division of labour and the construction of mathematical models. However, there are also similarities identified described as important aspects of modelling work in the different practices, such as communication, collaboration, projects, and the use of applying and adapting pre-defined models. Students, teachers and modellers expressed a variety of descriptions of what modelling means. The variety of descriptions in the workplace is not surprising, since their working approaches are quite different, but it makes the notion difficult to transpose into school practise. Questions raised are if it is unrealistic to search for a general definition and if it is really necessary to have a general definition. The consequence, for anyone how uses the notion, is to always be explicit with the meaning.An implication for teaching is that modelling as it shows in the workplace can never be fully ‘mapped’ in the mathematical classroom. However, it may be possible to ‘simulate’ such activity. Working with mathematical modelling in projects is suggested to simulate workplace activities, which include collaboration and communication between different participants. The modelling problems may for example involve economic and environmental decisions, to prepare students to be critically aware of the use of mathematics in private life and in society, where many decisions are based on mathematical models.
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