| 1. |
- Hansson, Björn, et al.
(författare)
-
A hypothesis for insulin resistance in primary human adipocytes involving MRTF-A and suppression of PPARγ
- 2020
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 533:1, s. 64-69
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is the main risk factor behind insulin resistance and type 2 diabetes. Still, the mechanism behind adipocyte dysfunction is not yet resolved. Recently, we reported that rapid actin remodeling correlates with adipose cell size changes after short-term overfeeding. Therefore, we hypothesized that the actin-driven myocardin-related transcription factor (MRTF-A) contributes to impaired mature adipocyte function. Primary human adipocytes were subjected to adenoviral overexpression of MRTF-A or MRTF-B, followed by Western blot analysis and tracer glucose uptake assay. Further, we assessed cell size distribution, insulin response, MRTF-A localization, actin organization and degree of polymerization in adipocytes isolated from Ob/Ob mice. Overexpression of MRTF-A, but not MRTF-B, markedly suppressed PPARγ expression. Further, MRTF-A expression resulted in decreased IRS-1 level, shifted phosphorylation of Akt (pS473/pT308), IRS-1 (pS302) and AS160 (pT642), and lowered insulin-stimulated glucose uptake. Hypertrophic adipocytes from Ob/Ob mice displayed an increased proportion of polymerized actin, and increased nuclear translocation of MRTF-A compared with control (Ob/+). Similar with human adipocytes overexpressing MRTF-A, adipocytes isolated from Ob/Ob mice had reduced expression of IRS-1 and PPARγ, as well as impaired insulin response. Together, these data demonstrate that MRTF-A negatively influences insulin sensitivity and the expression of key targets in fully mature human adipocytes. This suggests that MRTF-A is poised to exert a transcriptional response in hypertrophic adipocytes, contributing to adipocyte dysfunction and insulin resistance.
|
|
| 2. |
- Hansson, Björn, et al.
(författare)
-
Adipose cell size changes are associated with a drastic actin remodeling
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Adipose tissue plays a major role in regulating whole-body insulin sensitivity and energy metabolism. To accommodate surplus energy, the tissue rapidly expands by increasing adipose cell size (hypertrophy) and cell number (hyperplasia). Previous studies have shown that enlarged, hypertrophic adipocytes are less responsive to insulin, and that adipocyte size could serve as a predictor for the development of type 2 diabetes. In the present study, we demonstrate that changes in adipocyte size correlate with a drastic remodeling of the actin cytoskeleton. Expansion of primary adipocytes following 2 weeks of high-fat diet (HFD)-feeding in C57BL6/J mice was associated with a drastic increase in filamentous (F)-actin as assessed by fluorescence microscopy, increased Rho-kinase activity, and changed expression of actin-regulating proteins, favoring actin polymerization. At the same time, increased cell size was associated with impaired insulin response, while the interaction between the cytoskeletal scaffolding protein IQGAP1 and insulin receptor substrate (IRS)-1 remained intact. Reversed feeding from HFD to chow restored cell size, insulin response, expression of actin-regulatory proteins and decreased the amount of F-actin filaments. Together, we report a drastic cytoskeletal remodeling during adipocyte expansion, a process which could contribute to deteriorating adipocyte function.
|
|
| 3. |
- Hansson, Björn, et al.
(författare)
-
Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat feeding
- 2018
-
Ingår i: Journal of Molecular Endocrinology. - 0952-5041. ; 60:3, s. 199-211
-
Tidskriftsartikel (refereegranskat)abstract
- To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and Western blotting, and confocal microscopy was used to assess autophagic activity. Switching to HFD was accompanied by an immediate adipocyte size expansion and onset of systemic insulin resistance already after two days, followed by recruitment of new adipocytes. Despite an initially increased non-stimulated and preserved insulin-stimulated glucose uptake, we observed a decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and protein kinase B (PKB). After 14 days of HFD, both the insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) and glucose uptake was blunted. RNA-seq analysis of adipose tissue revealed transient changes in gene expression at day four, including highly significant upregulation of Trp53inp, previously demonstrated to be involved in autophagy. We confirmed increased autophagy, measured as an increased density of LC3-positive puncta and decreased p62 expression after 14 days of HFD. In conclusion, HFD rapidly induced systemic insulin resistance, whereas insulin-stimulated glucose uptake remained intact throughout 6 days of HFD feeding. We also identified autophagy as an early cellular process that potentially influences adipocyte function upon switching to HFD.
|
|
| 4. |
- Morén, Björn, et al.
(författare)
-
EHD2 regulates adipocyte function and is enriched at cell surface-associated lipid droplets in primary human adipocytes
- 2019
-
Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 30:10, s. 1147-1159
-
Tidskriftsartikel (refereegranskat)abstract
- Adipocytes play a central role in energy balance, and dysfunctional adipose tissue severely affects systemic energy homeostasis. The ATPase EH domain-containing 2 (EHD2) has previously been shown to regulate caveolae, plasma membrane-specific domains that are involved in lipid uptake and signal transduction. Here, we investigated the role of EHD2 in adipocyte function. We demonstrate that EHD2 protein expression is highly up-regulated at the onset of triglyceride accumulation during adipocyte differentiation. Small interfering RNA-mediated EHD2 silencing affected the differentiation process and impaired insulin sensitivity, lipid storage capacity, and lipolysis. Fluorescence imaging revealed localization of EHD2 to caveolae, close to cell surface-associated lipid droplets in primary human adipocytes. These lipid droplets stained positive for glycerol transporter aquaporin 7 and phosphorylated perilipin-1 following adrenergic stimulation. Further, EHD2 overexpression in human adipocytes increased the lipolytic signaling and suppressed the activity of transcription factor PPAR.. Overall, these data suggest that EHD2 plays a key role for adipocyte function.
|
|
| 5. |
- Morén, Björn, 1987-, et al.
(författare)
-
Technical note: evaluation of a spatial optimization model for prostate high dose‐rate brachytherapy in a clinical treatment planning system
- 2023
-
Ingår i: Medical physics (Lancaster). - : WILEY. - 0094-2405 .- 2473-4209. ; 50:2, s. 688-693
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSpatial properties of a dose distribution, such as volumes of contiguous hot spots, are of clinical importance in treatment planning for high dose-rate brachytherapy (HDR BT). We have in an earlier study developed an optimization model that reduces the prevalence of contiguous hot spots by modifying a tentative treatment plan. PurposeThe aim of this study is to incorporate the correction of hot spots in a standard inverse planning workflow and to validate the integrated model in a clinical treatment planning system. The spatial function is included in the objective function for the inverse planning, as opposed to in the previous study where it was applied as a separate post-processing step. Our aim is to demonstrate that fine-adjustments of dose distributions, which are often performed manually in todays clinical practice, can be automated. MethodsA spatial optimization function was introduced in the treatment planning system RayStation (RaySearch Laboratories AB, Stockholm, Sweden) via a research interface. A series of 10 consecutive prostate patients treated with HDR BT was retrospectively replanned with and without the spatial function. ResultsOptimization with the spatial function decreased the volume of the largest contiguous hot spot by on average 31%, compared to if the function was not included. The volume receiving at least 200% of the prescription dose decreased by on average 11%. Target coverage, measured as the fractions of the clinical target volume (CTV) and the planning target volume (PTV) receiving at least the prescription dose, was virtually unchanged (less than a percent change for both metrics). Organs-at-risk received comparable or slightly decreased doses if the spatial function was included in the optimization model. ConclusionsOptimization of spatial properties such as the volume of contiguous hot spots can be integrated in a standard inverse planning workflow for brachytherapy, and need not be conducted as a separate post-processing step.
|
|
| 6. |
- Akerblom, H., et al.
(författare)
-
Association of Gastric Bypass Surgery With Risk of Developing Diabetic Retinopathy Among Patients With Obesity and Type 2 Diabetes in Sweden: An Observational Study
- 2021
-
Ingår i: Jama Ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 139:2, s. 200-205
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Knowledge of the incidence and progression of diabetic retinopathy (DR) after gastric bypass surgery (GBP) in patients with obesity and diabetes could guide the management of these patients. OBJECTIVE To investigate the incidence of diabetic ocular complications in patients with type 2 diabetes after GBP compared with the incidence of diabetic ocular complications in a matched cohort of patients with obesity and diabetes who have not undergone GBP. DESIGN, SETTING, AND PARTICIPANTS Data from 2 nationwide registers in Sweden, the Scandinavian Obesity Surgery Registry and the National Diabetes Register, were used for this cohort study. A total of 5321 patients with diabetes from the Scandinavian Obesity Surgery Registry who had undergone GBP from January 1, 2007, to December 31, 2013, were matched with 5321 patients with diabetes from the National Diabetes Register who had not undergone GBP, based on sex, age, body mass index (BMI), and calendar time (2007-2013). Follow-up data were obtained until December 31, 2015. Statistical analysis was performed from October 5, 2018, to September 30, 2019. EXPOSURE Gastric bypass surgery. MAIN OUTCOMES AND MEASURES Incidence of new DR and other diabetic ocular complications. RESULTS The study population consisted of 5321 patients who had undergone GBP (3223 women [60.6%]; mean [SD] age, 49.0 [9.5] years) and 5321 matched controls (3395 women [63.8%]; mean [SD] age, 47.1 [11.5] years). Mean (SD) follow-up was 4.5 (1.6) years. The mean (SD) BMI and hemoglobin A1c concentration at baseline were 42.0 (5.7) and 7.6%(1.5%), respectively, in the GBP group and 40.9 (7.3) and 7.5%(1.5%), respectively, in the control group. The mean (SD) duration of diabetes was 6.8 (6.3) years in the GBP group and 6.4 (6.4) years in the control group. The risk for new DR was reduced in the patients who underwent GBP (hazard ratio, 0.62 [95% CI, 0.49-0.78]; P <.001). The dominant risk factors for development of DR at baseline were diabetes duration, hemoglobin A1c concentration, use of insulin, glomerular filtration rate, and BMI. CONCLUSIONS AND RELEVANCE This nationwide matched cohort study suggests that there is a reduced risk of developing new DR associated with GBP, and no evidence of an increased risk of developing DR that threatened sight or required treatment. (c) 2021 American Medical Association. All rights reserved.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Avery, Rachael S., et al.
(författare)
-
A 725-year integrated offshore terrestrial varve chronology for southeastern Sweden suggests rapid ice retreat ~ 15 ka BP
- 2021
-
Ingår i: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 50:2, s. 477-496
-
Tidskriftsartikel (refereegranskat)abstract
- The Swedish Varve Chronology is an unparalleled tool for linking the deglacial history of Sweden with associated palaeo-environmental change at an annual time scale, and it forms part of Sweden's cultural heritage. A full deglacial chronology connected to the present day does not yet exist; a notable gap is in southeasternmost Sweden, where few varved records are successfully connected to reconstruct ice-margin retreat. Deglaciation in southern Sweden covers both the climate transition to the Bølling warm period (similar to 14.7 ka BP) and the ice-margin transition from a subaqueous to terrestrial terminus. To facilitate investigations into the links between ice-margin dynamics and abrupt climate change, we revisited the varve chronologies of southern Sweden. We digitized unpublished records, reanalysed existing varve thickness records, and obtained and analysed new varve series both on land and offshore. This combined approach has enabled us to refine and extend the existing south coast chronology east and 78 km northwards. Our new Skåne-Småland chronology records 725 years of deglaciation, in addition to a younger floating chronology in parts. This chronology suggests that the glacial-lake terminating Fennoscandian Ice Sheet in southern Sweden initially retreated northwards at similar to 110-160 m a(-1) slowing to 60-70 m a(-1) near the palaeo-shoreline. Between today's mainland and the (now) island of Öland the retreat rates increase three- to fivefold. Ice-margin retreat was initially oriented towards the north (as along the south coast), but later pivoted towards the northwest, signifying a landward retreat of terrestrial 'Swedish' ice that became divorced from the Baltic Sea ice-sheet catchment. Our new 725-year-long varve thickness series reveals repeated multidecadal scale episodes of increased sedimentation. These likely signify phases of enhanced ice-sheet melting that repeat and persist throughout the deglaciation of Skåne-Småland.
|
|
| 11. |
- Blom, Björn, et al.
(författare)
-
Analys av generativa mekanismer
- 2008
-
Ingår i: Att forska i socialt arbete. - : Studentlitteratur, Lund. - 9789144004624
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 12. |
- Blom, Björn, 1965-, et al.
(författare)
-
Analysis of generative mechanisms
- 2011
-
Ingår i: Journal of Critical Realism. - London : Equinox Publishing. - 1476-7430 .- 1572-5138. ; 10:1, s. 60-79
-
Tidskriftsartikel (refereegranskat)abstract
- The focus of this article is the analysis of generative mechanisms, a basic concept and phenomenon within the metatheoretical perspective of critical realism. It is emphasized that research questions and methods, as well as the knowledge it is possible to attain, depend on the basic view – ontologically and epistemologically – regarding the phenomenon under scrutiny. A generative mechanism is described as a trans empirical but real existing entity, explaining why observable events occur. Mechanisms are mostly possible to grasp only indirectly by analytical work (theory-building), based however on empirical observations. In order to achieve such an explanatory analysis, five methodological steps are suggested and discussed, among them abduction and retroduction. These steps are illustrated throughout by examples drawn from empirical research regarding social work practice. The article is concluded with a discussion of the need for knowledge of generative mechanisms.
|
|
| 13. |
|
|
| 14. |
- Blom, Björn, 1965-, et al.
(författare)
-
Evaluation of quality in social-work practice
- 2012
-
Ingår i: Nordic Journal of Social Research. - Lillehammer, Norge : The Centre for Innovation in Services (CIS). - 1892-2783. ; 3, s. 1-17
-
Tidskriftsartikel (refereegranskat)abstract
- This theoretical article describes and discusses the concept of quality in relation to the evaluation of social-work practice. Of particular interest are the difference between quality of services and quality of life and the importance of balancing the stakeholders’ different interests in order to make a sound judgement of quality in social work possible. This article begins with presenting some basic perspectives on quality as well as the transference of the concept of quality from manufacturing industry to social-work practice. Thereafter the two main issues are discussed: the concepts of quality of service and of quality of life and the importance of balancing different stakeholders’ perspectives in the evaluation of quality in social-work practice. This article concludes that: 1) it is crucial to be aware of and to consider the distinction between quality of service and quality of life; 2) clients’ perspective on quality of life is an aspect of outcome that currently receives insufficient attention; 3) clients’ subjective experiences of welfare of well-being deserve greater attention for ethical as well as methodological reasons; and 4) judgement of quality in social work are inevitably dependent on different stakeholders’ perspectives.
|
|
| 15. |
- Blom, Björn, 1965-, et al.
(författare)
-
Explaining social work practice : the CAIMeR theory
- 2015
-
Ingår i: Social work research. - : Sage Publications. - 9781446295793 ; , s. 239-260
-
Bokkapitel (refereegranskat)abstract
- Summary: This article presents the CAIMeR theory, consisting of a conceptual framework and a theoretical model, which can help explain how results in social work practice arise from interventions and its contextual contingencies. The theory has been developed over several years in connection with empirical studies, and together with social workers. Findings: The article starts from the meta-theoretical perspective critical realism and its notion of explanative knowledge as a stepping stone to open up the so-called black box. A fundamental concept in critical realism, generative mechanisms, is discussed and elaborated. Applications: The CAIMeR theory can be used in several contexts: social work practice, and for evaluation of social work, and, moreover, for organization development in social work. We argue that social workers, evaluators and decision-makers need accurate theory about the core activity (work with clients) within its contextual conditions. The CAIMeR theory pays attention to generative mechanisms at different levels, which is necessary if one wants to understand what is going on in a certain agency, and explain the results in a more qualified way. The theory can also be useful for researchers and university students that need a comprehensive explanative framework when studying phenomena in social work practice.
|
|
| 16. |
- Blom, Björn, 1965-, et al.
(författare)
-
Explaining social work practice : The CAIMeR theory
- 2010
-
Ingår i: Journal of Social Work. - : Sage. - 1468-0173 .- 1741-296X. ; 10:1, s. 98-119
-
Tidskriftsartikel (refereegranskat)abstract
- • Summary: This article presents the CAIMeR theory, consisting of a conceptual framework and a theoretical model, which can help explain how results in social work practice arise from interventions and its contextual contingencies. The theory has been developed over several years in connection with empirical studies, and together with social workers. • Findings: The article starts from the meta-theoretical perspective critical realism and its notion of explanative knowledge as a stepping stone to open up the so-called black box. A fundamental concept in critical realism, generative mechanisms, is discussed and elaborated. • Applications : The CAIMeR theory can be used in several contexts: social work practice, and for evaluation of social work, and, moreover, for organization development in social work. We argue that social workers, evaluators and decision-makers need accurate theory about the core activity (work with clients) within its contextual conditions. The CAIMeR theory pays attention to generative mechanisms at different levels, which is necessary if one wants to understand what is going on in a certain agency, and explain the results in a more qualified way. The theory can also be useful for researchers and university students that need a comprehensive explanative framework when studying phenomena in social work practice.
|
|
| 17. |
|
|
| 18. |
- Blom, Björn, 1965-, et al.
(författare)
-
Hur bör socialtjänstens IFO organiseras?
- 2011
-
Ingår i: Tidskriften Socionomen. - Stockholm : Akademikerförbundet SSR. - 0283-1929. ; :4, s. 12-16
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 19. |
|
|
| 20. |
- Blom, Björn, 1965-, et al.
(författare)
-
Inledning : Utvärdering i socialt arbete
- 2011. - 1
-
Ingår i: Utvärdering i socialt arbete. - Stockholm : Natur & Kultur. - 9789127119826 ; , s. 17-33
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Blom, Björn, 1965-, et al.
(författare)
-
Kritisk realistisk utvärdering
- 2011. - 1
-
Ingår i: Utvärdering i socialt arbete. - Stockholm : Natur & Kultur. - 9789127119826 ; , s. 139-154
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Blom, Björn, 1965-, et al.
(författare)
-
Kvalitetsbegreppet
- 2011. - 1
-
Ingår i: Utvärdering i socialt arbete. - Stockholm : Natur & Kultur. - 9789127119826 ; , s. 71-87
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 28. |
- Blom, Björn, 1965-, et al.
(författare)
-
Olikheter och beröringspunkter
- 2013. - 2
-
Ingår i: Kunskap i socialt arbete. - Stockholm : Natur och kultur. - 9789127134065 ; , s. 176-179
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 29. |
|
|
| 30. |
- Blom, Björn, 1965-, et al.
(författare)
-
Perspektiv och utvecklingslinjer
- 2013. - 2
-
Ingår i: Kunskap i socialt arbete. - Stockholm : Natur och kultur. - 9789127134065 ; , s. 79-82
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 31. |
|
|
| 32. |
- Blom, Björn, 1965-, et al.
(författare)
-
Teori för socialt arbete
- 2015. - 1
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- I den här boken redovisas en teori som har ambitionen att både beskriva och förklara hur det sociala arbetet fungerar. Det är den första svenska boken i sitt slag som presenterar teori utvecklad specifikt ur och för det sociala arbetets praktik. En av grundfrågorna är: Hur kan man förklara hur resultat i socialt arbete uppstår som en följd av socialarbetares och klienters insatser under vissa kontextuella villkor? Teorin går under benämningen KAIMeR, vilket innebär att den på ett systematiskt och sammanhållet sätt beaktar teori om kontext, aktörer, insatser, mekanismer och resultat. Ett centralt inslag är begreppet generativa mekanismer, med vars hjälp man kan fånga de ofta icke observerbara krafter som gör begripligt hur resultat i socialt arbete uppstår som en följd av insatser och kontextuella villkor. I boken beskrivs också en domänteori som klargör hur socialarbetares professionsutövning betingas av politik, förvaltning och institutionella förhållanden i samhället. Boken vänder sig till studerande i socialt arbete och angränsande områden, men även till forskare, chefer och socialarbetare verksamma inom det sociala arbetets område.
|
|
| 33. |
- Blom, Björn, 1965-, et al.
(författare)
-
Theory for social work practice
- 2019. - 1
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- This book presents a theory with the ambition of both describing and explaining the nature of social-work practice. It is the first book that presents an explanative theory developed specifically from and for social-work practice.One of the fundamental questions is: How can we explain how results in social-work practice emanate from social worker's and clients' actions under certain contextual conditions?The theory presented in this book is named CAIMeR, which means that it takes a systematic and coherent approach to the theory of Contexts, Actors, Interventions, Mechanisms and Results. The meta-theoretical basis is critical realism, where a key feature is the concept of generative mechanisms. This perspective can help us capture the often unobservable powers that explain how results in social work emerge as a consequence of interventions and contextual conditions. The book also presents a domain theory that explains how social workers' professional practice is conditioned by politics, management and institutional conditions.This book is essential reading for students in social work and adjoining disciplines, but also for researchers, managers and professional social workers.
|
|
| 34. |
|
|
| 35. |
- Dohlmar, Frida, et al.
(författare)
-
Validation of automated post-adjustments of HDR prostate brachytherapy treatment plans by quantitative measures and oncologist observer study
- 2023
-
Ingår i: Brachytherapy. - : Elsevier BV. - 1538-4721 .- 1873-1449. ; 22:3, s. 407-415
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim was to evaluate a postprocessing optimization algorithm's ability to improve the spatial properties of a clinical treatment plan while preserving the target coverage and the dose to the organs at risk. The goal was to obtain a more homogenous treatment plan, minimizing the need for manual adjustments after inverse treatment planning. MATERIALS AND METHODS: The study included 25 previously treated prostate cancer pa-tients. The treatment plans were evaluated on dose-volume histogram parameters established clin-ical and quantitative measures of the high dose volumes. The volumes of the four largest hot spots were compared and complemented with a human observer study with visual grading by eight oncologists. Statistical analysis was done using ordinal logistic regression. Weighted kappa and Fleiss' kappa were used to evaluate intra-and interobserver reliability. RESULTS: The quantitative analysis showed that there was no change in planning target volume (PTV) coverage and dose to the rectum. There were significant improvements for the adjusted treatment plan in: V150% and V200% for PTV, dose to urethra, conformal index, and dose nonhomogeneity ratio. The three largest hot spots for the adjusted treatment plan were significantly smaller compared to the clinical treatment plan. The observers preferred the adjusted treatment plan in 132 cases and the clinical in 83 cases. The observers preferred the adjusted treatment plan on homogeneity and organs at risk but preferred the clinical plan on PTV coverage. CONCLUSIONS: Quantitative analysis showed that the postadjustment optimization tool could improve the spatial properties of the treatment plans while maintaining the target coverage.
|
|
| 36. |
|
|
| 37. |
- Fryklund, Claes, et al.
(författare)
-
EH Domain-Containing 2 Deficiency Restricts Adipose Tissue Expansion and Impairs Lipolysis in Primary Inguinal Adipocytes
- 2021
-
Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid uptake can be facilitated via caveolae, specific plasma membrane invaginations abundantly expressed in adipocytes. The dynamin-related protein EH domain-containing 2 (EHD2) stabilizes caveolae at the cell surface. Here, we have examined the importance of EHD2 for lipid handling using primary adipocytes isolated from EHD2 knockout (Ehd2−/−) C57BL6/N mice. Following high-fat diet (HFD) feeding, we found a clear impairment of epididymal, but not inguinal, adipose tissue expansion in Ehd2−/− compared with Ehd2+/+ (WT) mice. Cell size distribution analysis revealed that Ehd2−/− mice had a lower proportion of small adipocytes, and an accumulation of medium-sized adipocytes in both epididymal and inguinal adipose tissue. Further, PPARγ activity, FABP4 and caveolin-1 expression were decreased in adipocytes isolated from Ehd2−/− mice. Inguinal adipocytes isolated from Ehd2−/− mice displayed reduced lipolysis in response to beta adrenergic receptor agonist, which was associated with reduced phosphorylation of perilipin-1 and hormone sensitive lipase (HSL). This impairment could not be rescued using a cAMP analog, indicating that impaired lipolysis in Ehd2−/− primary adipocytes likely occurs at the level of, or downstream of, protein kinase A (PKA). Altogether, these findings pinpoint the importance of EHD2 for maintained intracellular lipid metabolism, and emphasize differences in mechanisms regulating lipid handling in various adipose-tissue depots.
|
|
| 38. |
- Fryklund, Claes, et al.
(författare)
-
Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice
- 2022
-
Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- To accommodate surplus energy, the adipose tissue expands by increasing adipocyte size (hypertrophy) and number (hyperplasia). The presence of hypertrophic adipocytes is a key characteristic of adipose tissue dysfunction. High-fat diet (HFD) fed C57BL/6J mice are a commonly used model to study obesity and obesity-related complications. In the present study, we have characterized adipose plasticity, at both the cellular and tissue level, by examining the temporal development of systemic insulin resistance and adiposity in response to HFD-feeding for 4, 8, and 12 weeks (4w, 8w, and 12w). Within the same time frame, we examined systemic metabolic flexibility and adipose plasticity when switching from HFD- to chow-diet during the last 2 weeks of diet intervention (referred to as the reverse (REV) group: 4wREV (2w HFD+2w chow), 8wREV (6w HFD+2w chow), 12wREV (10w HFD+2w chow)). In response to HFD-feeding over time, the 12w group had impaired systemic insulin sensitivity compared to both the 4w and 8w groups, accompanied by an increase in hypertrophic inguinal adipocytes and liver triglycerides. After reversing from HFD- to chow-feeding, most parameters were completely restored to chow control levels for 4wREV and 8wREV groups. In contrast, the 12wREV group had a significantly increased number of hypertrophic adipocytes, liver triglycerides accumulation, and impaired systemic insulin sensitivity compared to chow-fed mice. Further, image analysis at the single-cell level revealed a cell-size dependent organization of actin filaments for all feeding conditions. Indeed, the impaired adipocyte size plasticity in the 12wREV group was accompanied by increased actin filamentation and reduced insulin-stimulated glucose uptake compared with chow-fed mice. In summary, these results demonstrate that the C57BL/6J HFD-feeding model has a large capacity to restore adipocyte cell size and systemic insulin sensitivity, and that a metabolic tipping point occurs between 8 and 12w of HFD-feeding where this plasticity deteriorates. We believe these findings provide substantial understanding of C57BL/6J mice as an obesity model, and that an increased pool of hypertrophic ING adipocytes could contribute to aggravated insulin resistance.
|
|
| 39. |
- Fryklund, Claes, et al.
(författare)
-
Impaired glucose transport in inguinal adipocytes after short-term high-sucrose feeding in mice
- 2020
-
Ingår i: Journal of Nutritional Biochemistry. - : Elsevier BV. - 0955-2863. ; 78
-
Tidskriftsartikel (refereegranskat)abstract
- Diets enriched in sucrose severely impair metabolic regulation and are associated with obesity, insulin resistance and glucose intolerance. In the current study, we investigated the effect of 4 weeks high-sucrose diet (HSD) feeding in C57BL6/J mice, with specific focus on adipocyte function. Mice fed HSD had slightly increased adipose tissue mass but displayed similar hepatic triglycerides, glucose and insulin levels, and glucose clearance capacity as chow-fed mice. Interestingly, we found adipose depot-specific differences, where both the non- and insulin-stimulated glucose transports were markedly impaired in primary adipocytes isolated from the inguinal fat depot from HSD-fed mice. This was accompanied by decreased protein levels of both GLUT4 and AS160. A similar but much less pronounced trend was observed in the retroperitoneal depot. In contrast, both GLUT4 expression and insulin-stimulated glucose uptake were preserved in adipocytes isolated from epididymal adipose tissue with HSD. Further, we found a slight shift in cell size distribution towards larger cells with HSD and a significant decrease of ACC and PGC-1α expression in the inguinal adipose tissue depot. Moreover, fructose alone was sufficient to decrease GLUT4 expression in cultured, mature adipocytes. Altogether, we demonstrate that short-term HSD feeding has deleterious impact on insulin response and glucose transport in the inguinal adipose tissue depot, specifically. These changes occur before the onset of systemic glucose dysmetabolism and therefore could provide a mechanistic link to overall impaired energy metabolism reported after prolonged HSD feeding, alone or in combination with HFD.
|
|
| 40. |
- Fryklund, Claes, et al.
(författare)
-
Rosiglitazone treatment enhances intracellular actin dynamics and glucose transport in hypertrophic adipocytes
- 2022
-
Ingår i: Life Sciences. - : Elsevier BV. - 0024-3205. ; 299
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To accommodate surplus energy, adipose tissue expands by increasing both adipose cell size (hypertrophy) and cell number (hyperplasia). Enlarged, hypertrophic adipocytes are known to have reduced insulin response and impaired glucose transport, which negatively influence whole-body glucose homeostasis. Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, known to stimulate hyperplasia and to efficiently improve insulin sensitivity. Still, a limited amount of research has investigated the effects of rosiglitazone in mature, hypertrophic adipocytes. Therefore, the objective of this study was to examine rosiglitazone's effect on insulin-stimulated glucose uptake in hypertrophic adipocytes. Main methods: C57BL/6J male mice were subjected to 2 weeks of high-fat diet (HFD) followed by 1 week of HFD combined with daily administration of rosiglitazone (10 mg/kg). Adipose cell-size distribution and gene expression were analysed in intact adipose tissue, and glucose uptake, insulin response, and protein expression were examined using primary adipocytes isolated from epididymal and inguinal adipose tissue. Key findings: HFD-feeding induced an accumulation of hypertrophic adipocytes, which was not affected by rosiglitazone-treatment. Still, rosiglitazone efficiently improved insulin-stimulated glucose transport without restoring insulin signaling or GLUT4 expression in similar-sized adipocytes. This improvement occurred concurrently with extracellular matrix remodelling and restored intracellular levels of targets involved in actin turnover. Significance: These results demonstrate that rosiglitazone improves glucose transport in hypertrophic adipocytes, and highlights the importance of the cytoskeleton and extracellular matrix as potential therapeutic targets.
|
|
| 41. |
- Holt, Vance, et al.
(författare)
-
Acute cytokine treatment stimulates glucose uptake and glycolysis in human keratinocytes
- 2023
-
Ingår i: Cytokine. - : Elsevier BV. - 1043-4666. ; 161
-
Tidskriftsartikel (refereegranskat)abstract
- During inflammation, cellular glucose uptake and glycolysis are upregulated to meet an increased energy demand. For example, keratinocyte glycolysis is essential for progression of psoriasis. Therefore, understanding the regulation of glucose metabolism in keratinocytes is of importance. Here, we show that the pro-inflammatory cytokines IFNγ and TNF together rapidly induce glucose uptake, glycolysis, and glycolytic capacity in cultured keratinocytes. Furthermore, we found that acute IFNγ and TNF stimulation induces glucose transporter 4 (GLUT4) translocation to the plasma membrane and engages AMPK-dependent intracellular signaling. Together, these findings suggest acute cytokine-induced glucose metabolism in keratinocytes could contribute to inflammation in psoriatic disease, and that GLUT4 is involved in these processes.
|
|
| 42. |
|
|
| 43. |
- Kotowska, Dorota, et al.
(författare)
-
Short-term lingonberry feeding is associated with decreased insulin levels and altered adipose tissue function in high-fat diet fed C57BL/6J mice
- 2022
-
Ingår i: Journal of Functional Foods. - : Elsevier BV. - 1756-4646. ; 94, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Intact adipose tissue function is essential to maintain glucose and lipid homeostasis. To study the impact of altered adipose tissue function on whole-body metabolism, diet-induced obesity in mice is frequently used as a model organism. In the current study, we have examined health-promoting effects of a lingonberry supplemented diet. We found C57BL/6J mice fed a high-fat diet supplemented with lingonberry for 4 days to have significantly lowered body-weight gain, adipose tissue expansion, and reduced insulin levels, compared to mice fed an isocaloric high-fat diet. RNA-Seq analysis of epididymal adipose tissue revealed differential expression of genes related to mitochondria fission (Mief1, Dnm1, Vps35, and Opa1). Further, we detected increased gene expression and phosphorylation of perilipin-1 (pS522), and increased lipolysis in primary adipocytes from lingonberry-fed mice. Together, these data pinpoint that beneficial effects of a lingonberry enriched diet are rapidly detectable and that the adipose tissue constitutes a target for these effects.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
- Lalos, Ann, 1953-, et al.
(författare)
-
Socialt arbete i hälso- och sjukvård : Villkor, innehåll och utmaningar
- 2014. - 1
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- I Sverige bedrivs socialt arbete på flera arenor, inte minst inom hälso- och sjukvård där kuratorn har en central roll. Socialt arbete i hälso- och sjukvård är den första svenska läroboken som tar ett brett grepp om ämnet utifrån ett kritiskt förhållningssätt. Boken består av tre delar där den första belyser fältet ur historiskt, organisatoriskt, teoretiskt, juridiskt och professionellt perspektiv. I den andra delen tas kuratorns konkreta verksamhetsområde upp. Här beskrivs arbetet med särskilda patientkategorier som till exempel sjuka barn och äldre, beroendeproblematik, psykisk ohälsa, cancer, kris och sorg. Slutligen berörs specifika utmaningar, så som nya patient kategorier, etiska dilemman, krav på evidens och andra förändringar av kuratorsrollen i en telemedicinsk och globaliserad värld. Författarna till Socialt arbete i hälso- och sjukvård riktar sig främst till studerande inom socialt arbete, medicin och vård samt till kuratorer och andra yrkesverksamma inom hälso- och sjukvård, socialtjänst och social omsorg.
|
|
| 47. |
- Larsson, Elin, et al.
(författare)
-
An EH-domain switching mechanism regulates stable membrane association of EHD2
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- EHD2 is a dimeric ATPase known to stabilise the surface connection of the characteristic small invaginations of the cell surface termed caveolae. EHD2 oligomerises into rings around lipid membranes thereby controlling their shape. Here, we have analysed the domain interactions and mechanism that control the stable membrane association of EHD2 at caveolae. We have found that the N-terminus of EHD2, which is buried in the core protein and obstruct assembly, has to be relieved by an EH domain dependent mechanism. The binding between the EH domain and a loop in the GTPase domain of EHD2 was required for stable membrane association, but the loop in itself was not sufficient for specific recruitment to caveolae. A positively charged stretch in the EH domain is proposed to bind to lipids and thereby influence the exchange rate of EHD2. Taken together, we propose a stringent regulatory mechanism for the assembly of EHD2 involving switching of the EH domain position to release the N-terminus and facilitate oligomerisation.
|
|
| 48. |
- Larsson, Elin, et al.
(författare)
-
Dynamin2 functions as an accessory protein to reduce the rate of caveola internalization
- 2023
-
Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 222:4
-
Tidskriftsartikel (refereegranskat)abstract
- Caveolae are small membrane invaginations that generally are stably attached to the plasma membrane. Their release is believed to depend on the GTPase dynamin 2 (Dyn2), in analogy with its role in fission of clathrin-coated vesicles. The mechanistic understanding of caveola fission is, however, sparse. Here, we used microscopy-based tracking of individual caveolae in living cells to determine the role of Dyn2 in caveola dynamics. We report that Dyn2 stably associated with the bulb of a subset of caveolae, but was not required for formation or fission of caveolae. Dyn2-positive caveolae displayed longer plasma membrane duration times, whereas depletion of Dyn2 resulted in shorter duration times and increased caveola fission. The stabilizing role of Dyn2 was independent of its GTPase activity and the caveola stabilizing protein EHD2. Thus, we propose that, in contrast to the current view, Dyn2 is not a core component of the caveolae machinery, but rather functions as an accessory protein that restrains caveola internalization.
|
|
| 49. |
- Lilja, Carl, et al.
(författare)
-
A Lateglacial-early Holocene tephrochronology for SW Sweden
- 2013
-
Ingår i: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 42:3, s. 544-554
-
Tidskriftsartikel (refereegranskat)abstract
- Four cores from southwestern Sweden are presented together with their tephra geochemistry. Two cryptotephra horizons were confirmed geochemically in the cores, the Vedde Ash and the Hässeldalen Tephra. The Lateglacial Hässeldalen Tephra (11 360–11 300 cal. a BP) offers great potential as a regional isochrone to add a new degree of certainty to the deglaciation chronology of southern Sweden, including the extent of glacial Lake Bolmen. In addition, the geographical distribution of the Hässeldalen Tephra has recently been extended outside of Sweden, making it an important time-marker horizon in northern Europe. There are potential difficulties, however. Proper identification of the actual isochrone is complicated by the vertical pattern of shard distribution, which could be the result of several eruptive events, as well as by the fact that shards from the 10-ka Askja horizon (10 500–10 350 cal. a BP) were found in close stratigraphical proximity. The geochemical data presented are the result of improved EPMA methodology, which significantly reduces sodium mobilization. The results therefore have slightly altered values, which has consequences for classifying new finds when they are compared with previous data for geochemically similar tephras. Finally, potential indications of the Borrobol/Penifiler horizon are presented, although the existence of the horizon could not be confirmed geochemically. This highlights the need to retrieve cores from different locations within a basin based on an analysis of basin morphology if horizons are to be located.
|
|
| 50. |
- Liu, Li, et al.
(författare)
-
Cell Type Dependent Suppression of Inflammatory Mediators by Myocardin Related Transcription Factors
- 2021
-
Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Myocardin related transcription factors (MRTFs: MYOCD/myocardin, MRTF-A, and MRTF-B) play a key role in smooth muscle cell differentiation by activating contractile genes. In atherosclerosis, MRTF levels change, and most notable is a fall of MYOCD. Previous work described anti-inflammatory properties of MRTF-A and MYOCD, occurring through RelA binding, suggesting that MYOCD reduction could contribute to vascular inflammation. Recent studies have muddled this picture showing that MRTFs may show both anti- and pro-inflammatory properties, but the basis of these discrepancies remain unclear. Moreover, the impact of MRTFs on inflammatory signaling pathways in tissues relevant to human arterial disease is uncertain. The current work aimed to address these issues. RNA-sequencing after forced expression of myocardin in human coronary artery smooth muscle cells (hCASMCs) showed reduction of pro-inflammatory transcripts, including CCL2, CXCL8, IL6, and IL1B. Side-by-side comparison of MYOCD, MRTF-A, and MRTF-B in hCASMCs, showed that the anti-inflammatory impact was shared among MRTFs. Correlation analyses using human arterial transcriptomic datasets revealed negative correlations between MYOCD, MRTFA, and SRF, on the one hand, and the inflammatory transcripts, on the other. A pro-inflammatory drive from lipopolysaccharide, did not change the size of the suppressive effect of MRTF-A in hCASMCs on either mRNA or protein levels. To examine cell type-dependence, we compared the anti-inflammatory impact in hCASMCs, with that in human bladder SMCs, in endothelial cells, and in monocytes (THP-1 cells). Surprisingly, little anti-inflammatory activity was seen in endothelial cells and monocytes, and in bladder SMCs, MRTF-A was pro-inflammatory. CXCL8, IL6, and IL1B were increased by the MRTF-SRF inhibitor CCG-1423 and by MRTF-A silencing in hCASMCs, but depolymerization of actin, known to inhibit MRTF activity, had no stimulatory effect, an exception being IL1B. Co-immunoprecipitation supported binding of MRTF-A to RelA, supporting sequestration of this important pro-inflammatory mediator as a mechanism. Dexamethasone treatment and silencing of RelA (by 76 ± 1%) however only eliminated a fraction of the MRTF-A effect (≈25%), suggesting mechanisms beyond RelA binding. Indeed, SRF silencing suggested that MRTF-A suppression of IL1B and CXCL8 depends on SRF. This work thus supports an anti-inflammatory impact of MRTF-SRF signaling in hCASMCs and in intact human arteries, but not in several other cell types.
|
|
