| 1. |
- Månsson, Robert, et al.
(författare)
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Pearson correlation analysis of microarray data allows for the identification of genetic targets for early B-cell factor
- 2004
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 279:17, s. 17905-17913
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Tidskriftsartikel (refereegranskat)abstract
- B lymphocyte development is a complex biological process critically dependent on the transcription factor early B cell factor (EBF). To deepen understanding of the roles for EBF in this process, we have used Pearson correlation analysis to evaluate microarray data from a set of mouse B lymphoid cell lines representing different stages of development. Comparing the expression pattern of EBF to that of the other genes in the data set revealed that VpreB1, mb-1, and lambda5, all known target genes, presented high correlation values to EBF. High correlations were also seen for the VpreB3 and CD19 genes and biochemical as well as functional data supported that they are target genes for EBF even though the expression of CD19 was critically dependent of Pax-5. We also obtained evidence for extensive collaborative actions of EBF and E47 even though microarray analysis of hematopoetic progenitor cells ectopically expressing these proteins suggested that they activated only a subset of pre-B cell restricted genes.
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| 2. |
- Alyass, Akram, et al.
(författare)
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Modelling of OGTT curve identifies 1 h plasma glucose level as a strong predictor of incident type 2 diabetes: results from two prospective cohorts
- 2015
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 58:1, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The relevance of the OGTT in predicting type 2 diabetes is unclear. We assessed the performance of 14 OGTT glucose traits in type 2 diabetes prediction. Methods We studied 2,603 and 2,386 Europeans from the Botnia study and Malmo Prevention Project (MPP) cohorts with baseline OGTT data. Over a follow-up period of 4.94 years and 23.5 years, 155 (5.95%) and 467 (19.57%) participants, respectively, developed type 2 diabetes. The main outcome was incident type 2 diabetes. Results One-hour plasma glucose (1h-PG) was a fair/good predictor of incident type 2 diabetes in the Botnia study and MPP (AUC for receiver operating characteristic [AUC(ROC)] 0.80 [0.77, 0.84] and 0.70 [0.68, 0.73]). 1h-PG alone outperformed the prediction model of multiple clinical risk factors (age, sex, BMI, family history of type 2 diabetes) in the Botnia study and MPP (AUC(ROC) 0.75 [0.72, 0.79] and 0.67 [0.64, 0.70]). The same clinical risk factors added to 1h-PG modestly increased prediction for incident type 2 diabetes (Botnia, AUC(ROC) 0.83 [0.80, 0.86]; MPP, AUC(ROC) 0.74 [0.72, 0.77]). 1h-PG also outperformed HbA(1c) in predicting type 2 diabetes in the Botnia cohort. A 1h-PG value of 8.9 mmol/l and 8.4 mmol/l was the optimal cut-point for initial screening and selection of high-risk individuals in the Botnia study and MPP, respectively, and represented 30% and 37% of all participants in these cohorts. High-risk individuals had a substantially increased risk of incident type 2 diabetes (OR 8.0 [5.5, 11.6] and 3.8 [3.1, 4.7]) and captured 75% and 62% of all incident type 2 diabetes in the Botnia study and MPP. Conclusions/interpretation1h-PG is a valuable prediction tool for identifying adults at risk for future type 2 diabetes.
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| 3. |
- Arora, Geeti P, et al.
(författare)
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Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 286:2, s. 192-206
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population-based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia.METHODS: 85 GDM/T2D loci in European and/or Indian populations from previous studies were assessed for association with GDM based on Swedish GDM criteria in 4018 Punjabi Indian and 507 Swedish pregnant women. Selected loci were replicated in Scandinavian cohorts, Radiel (N=398, Finnish), STORK/STORK-G (N=780, Norwegian).RESULTS: Punjabi Indian women had higher GDM prevalence, lower insulin secretion and better insulin sensitivity than Swedish women. There were significant frequency differences of GDM/T2D risk alleles between both populations. rs7178572 at HMG20A, previously associated with GDM in South Indian and European women was replicated in North Indian women. The T2D risk SNP rs11605924 in the CRY2 gene was associated with increased GDM risk in Scandinavian but decreased risk in Punjabi Indian women. No other overlap was seen between GDM loci in both populations.CONCLUSIONS: GDM is more common in Indian than Swedish women, which partially can be attributed to differences in insulin secretion and action. There was marked heterogeneity in the GDM phenotypes between the populations which could only partially be explained by genetic differences. This article is protected by copyright. All rights reserved.
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| 4. |
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| 5. |
- Boström, Anita, 1957-, et al.
(författare)
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Förekomsten av våld i nära relationer bland äldre personer
- 2022
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Ingår i: Äldre personers utsatthet för våld i nära relationer. - : Studentlitteratur AB. - 9789144155142 ; , s. 31-64
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Frågor om våld i nära relationer är numera vanligt förekommande i media, politiska debatter, offentliga utredningar och lagändringar. Men trots detta uppmärksammas sällan äldre personers utsatthet för våld. Anledningarna kan vara flera, men tanken på att äldre kan utsättas för våld i en nära relation är för många avlägsen.Äldre personers utsatthet för våld i nära relationer vill synliggöra att olika typer av våld förekommer mot och bland äldre personer. Men det allra viktigaste är att ge kunskap om hur omgivningen kan uppmärksamma detta och förhindra våld, samt ge hjälp och stöd. Boken belyser det ansvar som olika myndigheter, såsom socialtjänst, hälso- och sjukvård samt tandvård, har. Ett kapitel beskriver rättsprocessen vid en anmälan och ett annat belyser vilka svårigheter en äldre person kan ha när det gäller att söka hjälp och att bryta upp från en relation. Flera kapitel innehåller konkreta råd för hur exempelvis personal kan ge hjälp och stöd.Äldre personers utsatthet för våld i nära relationer är i första hand skriven för högskoleutbildningar inom socialt arbete, vård, omsorg och medicin. Boken kan också vara till nytta för alla som vill öka sin kunskap om äldre personers utsatthet för våld i nära relationer.
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| 6. |
- Bunea, Ada-Ioana, et al.
(författare)
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Micropatterned Carbon-on-Quartz Electrode Chips for Photocurrent Generation from Thylakoid Membranes
- 2018
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Ingår i: ACS Applied Energy Materials. - : American Chemical Society (ACS). - 2574-0962. ; 1:7, s. 3313-3322
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Tidskriftsartikel (refereegranskat)abstract
- Harvesting the energy generated by photosynthetic organisms through light-dependent reactions is a significant step toward a sustainable future energy supply. Thylakoid membranes are the site of photosynthesis, and thus particularly suited for developing photo-bioelectrochemical cells. Novel electrode materials and geometries could potentially improve the efficiency of energy harvesting using thylakoid membranes. For commercial applications, electrodes with large surface areas are needed. Photolithographic patterning of a photoresist, followed by pyrolysis, is a flexible and fast approach for the fabrication of carbon electrodes with tailored properties. In this work, electrode chips consisting of patterned carbon supported on quartz were designed and fabricated. The patterned electrode area is 1 cm2, and the measurement chamber footprint is 0.5 cm2, 1 order of magnitude larger than previously tested electrodes for thylakoid membrane immobilization. The use of a transparent substrate allows back-side illumination, protecting the bioelectrochemical system from the environment and vice versa. Two different mediators, monomeric ([Ru(NH3)6]3+) and polymeric ([Os(2,2′-bipyridine)2-poly(N-vinylimidazole)10Cl]+/2+), are used for evaluating photocurrent generation from thylakoid membranes with different electrode geometries. Current densities up to 71 μA cm–2 are measured upon illumination through the transparent electrode chip with solar simulated irradiance (1000 W m–2).
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| 7. |
- Cousminer, Diana L, et al.
(författare)
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First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:11, s. 2396-2403
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODS: We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396).RESULTS: The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.CONCLUSIONS: Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.
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| 8. |
- Fall, Tove, et al.
(författare)
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Age- and sex-specific causal effects of adiposity on cardiovascular risk factors
- 2015
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 64:5, s. 1841-1852
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Tidskriftsartikel (refereegranskat)abstract
- Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
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| 9. |
- Gawlik, Kinga, et al.
(författare)
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Distinct roles for laminin globular domains in laminin alpha1 chain mediated rescue of murine laminin alpha2 chain deficiency.
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Laminin alpha2 chain mutations cause congenital muscular dystrophy with dysmyelination neuropathy (MDC1A). Previously, we demonstrated that laminin alpha1 chain ameliorates the disease in mice. Dystroglycan and integrins are major laminin receptors. Unlike laminin alpha2 chain, alpha1 chain binds the receptors by separate domains; laminin globular (LG) domains 4 and LG1-3, respectively. Thus, the laminin alpha1 chain is an excellent tool to distinguish between the roles of dystroglycan and integrins in the neuromuscular system. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide insights into the functions of laminin alpha1LG domains and the division of their roles in MDC1A pathogenesis and rescue. Overexpression of laminin alpha1 chain that lacks the dystroglycan binding LG4-5 domains in alpha2 chain deficient mice resulted in prolonged lifespan and improved health. Importantly, diaphragm and heart muscles were corrected, whereas limb muscles were dystrophic, indicating that different muscles have different requirements for LG4-5 domains. Furthermore, the regenerative capacity of the skeletal muscle did not depend on laminin alpha1LG4-5. However, this domain was crucial for preventing apoptosis in limb muscles, essential for myelination in peripheral nerve and important for basement membrane assembly. CONCLUSIONS/SIGNIFICANCE: These results show that laminin alpha1LG domains and consequently their receptors have disparate functions in the neuromuscular system. Understanding these interactions could contribute to design and optimization of future medical treatment for MDC1A patients.
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| 10. |
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| 11. |
- Gustafsson, Renata, et al.
(författare)
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Gene expression profiling of differentiating embryonic stem cells expressing dominant negative fibroblast growth factor receptor 2.
- 2007
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Ingår i: Matrix Biology. - : Elsevier BV. - 1569-1802 .- 0945-053X. ; 26, s. 197-205
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Tidskriftsartikel (refereegranskat)abstract
- Embryonic stein (ES) cells are derived from the inner cell mass of the blastocyst and can be cultured as three-dimensional embryoid bodies (EBs) in which embryonic pregastrulation stages are faithfully mimicked. Fibroblast growth factor receptors (mainly FGFR2) are involved in the first differentiation events during early mammalian embryogenesis. It has been demonstrated that the presence of FGFR2 is a prerequisite for laminin-111 and collagen type IV synthesis and subsequently basement membrane formation in EBs. To identify genes that are influenced by FGFR signalling, we performed global gene expression profiling of differentiating EBs expressing dominant negative FGFR2 (dnFGFR2), acquiring an extensive catalogue of down- and up-regulated genes. We show a strong down-regulation of endodermal and basement membrane related genes, which strengthen the view that the FGFR signalling pathway is a main stimulator of basement membrane synthesis in EBs. We further present down-regulation of genes previously not linked to FGFR signalling, and in addition an active transcription of some mesodermal related genes in differentiating dnFGFR2 EBs.
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| 12. |
- Hultman, Lill, et al.
(författare)
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"Som erfarenhetsforskare, då är man med och bestämmer i forskningsprojektet" : En autoetnografisk studie om en gemensam forskningsprocess
- 2022
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Ingår i: Socialvetenskaplig tidskrift. - : Linköping University Electronic Press. - 1104-1420 .- 2003-5624. ; 29:3-4, s. 305-324
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Tidskriftsartikel (refereegranskat)abstract
- In a participatory action research project, we emphasize experiences of collaboration between academic and community researchers by applying analytical autoethnography. The aim of the article is to describe the research process which involves both individual and collaborative processes, and to analyze challenges in relation to participation in the ongoing research process. We identified four themes: Start-up and initial challenges, Conditions and structural prerequisites for collaboration, Joint development of work methods and Power and role distribution. Our findings are presented in two separate analyses; a collaborative inductive analysis and an academic led theoretical analysis in which Arnstein’s ladder of participation and Fricker’s concept of epistemic injustice are utilized in order to scrutinize challenges related to different degrees of participation in the research process. The results demonstrate that shared hermeneutic resources are necessary for the mitigation of epistemic injustice and enablement of mutual learning processes, such as collective writing processes. The results also indicate that a full participation for community researchers in the entire research process was difficult to achieve, both in relation to structural resources such as allocated time, and in relation to perceptions of meaning- making aspects, for example, individual interests and contributions in terms of knowledge.
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| 13. |
- Hultman, Lill, et al.
(författare)
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"Som erfarenhetsforskare, då är man med och bestämmer i forskningsprojektet" : en autoetnografisk studie om en gemensam forskningsprocess
- 2023
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Ingår i: Socialvetenskaplig tidskrift. - : Linköping University Electronic Press. - 1104-1420 .- 2003-5624. ; 29:3-4, s. 305-324
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Tidskriftsartikel (refereegranskat)abstract
- In a participatory action research project, we emphasize experiences of collaboration between aca-demic and community researchers by applying analytical autoethnography. The aim of the article is to describe the research process which involves both individual and collaborative processes, and to analyze challenges in relation to participation in the ongoing research process. We identified four themes: Start-up and initial challenges, Conditions and structural prerequisites for collabo-ration, Joint development of work methods and Power and role distribution. Our findings are presented in two separate analyses; a collaborative inductive analysis and an academic led theore-tical analysis in which Arnstein’s ladder of participation and Fricker’s concept of epistemic injus-tice are utilized in order to scrutinize challenges related to different degrees of participation in the research process. The results demonstrate that shared hermeneutic resources are necessary for the mitigation of epistemic injustice and enablement of mutual learning processes, such as collective writing processes. The results also indicate that a full participation for community researchers in the entire research process was difficult to achieve, both in relation to structural resources such as allocated time, and in relation to perceptions of meaning- making aspects, for example, indivi-dual interests and contributionsin terms of knowledge.
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| 14. |
- Häger, Mattias, et al.
(författare)
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Cib2 binds integrin a7Bb1D and is reduced in laminin a2 chain deficient muscular dystrophy
- 2008
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:36, s. 24760-24769
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the gene encoding laminin alpha 2 chain cause congenital muscular dystrophy type 1A. In skeletal muscle, laminin alpha 2 chain binds at least two receptor complexes: the dystrophin-glycoprotein complex and integrin alpha 7 beta 1. To gain insight into the molecular mechanisms underlying this disorder, we performed gene expression profiling of laminin alpha 2 chain-deficient mouse limb muscle. One of the down-regulated genes encodes a protein called Cib2 (calcium-and integrin-binding protein 2) whose expression and function is unknown. However, the closely related Cib1 has been reported to bind integrin alpha IIb and may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel integrin alpha 7 beta 1-binding protein in muscle, we have studied Cib2 expression in the developing and adult mouse. Cib2 mRNA is mainly expressed in the developing central nervous system and in developing and adult skeletal muscle. In skeletal muscle, Cib2 colocalizes with the integrin alpha 7B subunit at the sarcolemma and at the neuromuscular and myotendinous junctions. Finally, we demonstrate that Cib2 is a calcium-binding protein that interacts with integrin alpha 7B beta 1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector of integrin alpha 7B beta 1D signaling in skeletal muscle.
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| 15. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 16. |
- Mansour Aly, Dina, et al.
(författare)
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Genome-wide association analyses highlight etiological differences underlying newly defined subtypes of diabetes
- 2021
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53, s. 1534-1542
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes has been reproducibly clustered into five subtypes with different disease progression and risk of complications; however, etiological differences are unknown. We used genome-wide association and genetic risk score (GRS) analysis to compare the underlying genetic drivers. Individuals from the Swedish ANDIS (All New Diabetics In Scania) study were compared to individuals without diabetes; the Finnish DIREVA (Diabetes register in Vasa) and Botnia studies were used for replication. We show that subtypes differ with regard to family history of diabetes and association with GRS for diabetes-related traits. The severe insulin-resistant subtype was uniquely associated with GRS for fasting insulin but not with variants in the TCF7L2 locus or GRS reflecting insulin secretion. Further, an SNP (rs10824307) near LRMDA was uniquely associated with mild obesity-related diabetes. Therefore, we conclude that the subtypes have partially distinct genetic backgrounds indicating etiological differences.
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| 17. |
- Mays, Christin
(författare)
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Have Money, Will Travel : Scholarships and Academic Exchange between Sweden and the United States, 1912–1980
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The large-scale transatlantic mobility of students, teachers, and researchers is a twentieth-century phenomenon that has contributed to the reshaping of international cultural, economic, and political relations into the twenty-first century. Through and as part of this development, the United States transformed into a powerful and influential country on the global stage. As a large, populous, and industrialized nation, the United States has been significant both as a funder of international mobility and as a destination for foreign students and scholars. Sweden, a small, peripheral country in Northern Europe, has had a long relationship with the United States. Amidst the mass migration of peoples from several European countries to North America in the mid-nineteenth century to the 1920s, over one million Swedes migrated to the United States. The connections made through this migration, combined with the growing economic, industrial, and cultural resources of the United States, led to a renewed desire to maintain and improve relations between the two countries from the early twentieth century.This study investigates the development of scholarship programs in Sweden and the United States and their role in the academic exchange between these two countries from 1912–1980. Set against broader cultural, economic, and political processes that increased the scale and complexity of academic mobility in the twentieth century, this study explains how scholarships facilitated and structured flows of people and knowledge. The relationships between three parts of scholarship programs are analyzed: their purposes, organizational frameworks and praxis, and scholarship awards. The analysis employs three points of departure: rationales for internationalization, historical institutionalism, and symbolic capital. Annual reports and scholarship holder documentation are the two main types of sources. Annual reports were used to create a historical timeline of the purposes that drove the founding of organizations and the establishment of scholarship programs to understand the institution of scholarship-funded academic mobility in the twentieth century. Scholarship holder documentation was used to create two datasets of scholarship awards from 1912–1944 and 1945–1979, which were analyzed using descriptive statistics to find patterns and trends in scholarship awards.The results show that the scholarship programs in this study structured complex and asymmetrical flows of people and knowledge between Sweden and the United States in the twentieth century. In the first period, private foundations were the main providers of scholarships and were steered by an array of cultural, academic, and economic purposes. After World War II, and especially during the Cold War, scholarship programs were submitted to the politicization and regulation of the United States government as transatlantic academic mobility became an increasingly widespread practice. The combined and overlapping purposes that steered scholarship-awarding from 1912–1980 facilitated the rise of particular individuals, types of knowledge, higher education institutions, and industries in Sweden and the United States. In addition, the asymmetrical distribution of these scholarships, in which three times as many Swedes traveled to the United States than the reverse, gradually structured a dependence on the academic, economic, and technological resources of the United States.
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| 18. |
- Mishra, Rajashree, et al.
(författare)
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Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:2, s. 418-425
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, β [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (β [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, β [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.
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| 19. |
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| 20. |
- Psilander, Niklas, et al.
(författare)
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The cross-education effect in men and woman after unilateral strength training and detraining
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionIt is well known that muscle strength increases in both the untrained and trained limb after a period of unilateral strength training. However, it is not known how this so called cross-education effect (CE-effect) is affected by a long period of detraining, and if there are any sex differences. Also, there are conflicting results regarding the effect of unilateral training on muscle mass in the untrained limb.AimThe primary objective was to study the CE-effect in men and women after a period of unilateral strength training and detraining. The secondary objective was to study if training one limb would affect the muscle mass of the homologous opposite limb.Method Sixteen untrained individuals, 9 females and 7 males, completed the study. The training intervention was 10 weeks (34 sessions) of unilateral strength training (leg press (LP) and leg extension (LE) exercise). 1RM and muscle thickness (vastus lateralis) were measured pre-, post- and 20 weeks post-training.Results Strength (1RM) in the trained leg increased for both men and woman (LP: ~60%, LE ~20%, p<0.01), with no sex differences. However, only the men had a strength increase in the untrained leg (LP: 26%, LE: 10%, p<0.05) and the non-significant increase observed for the woman (LP: 10%, LE: 3%) was significantly smaller than the increase in the men (p<0.05). Muscle thickness increased similarly for both men and women (trained leg: ~14%, p<0.01; untrained leg: ~4%, p<0.05). The detraining period did not affect strength, but muscle thickness was reduced close to pre-training values in both men and women.Conclusion The results of the present study show that the CE-effect is larger in men than women, and that it is long lasting (at least 20 weeks). Further, strength training of one leg can increase the muscle mass of the homologous opposite leg.
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| 21. |
- Slieker, Roderick C, et al.
(författare)
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Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes : an IMIRHAPSODY Study
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:11, s. 2683-2693
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.
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| 22. |
- Slieker, Roderick C, et al.
(författare)
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Identification of biomarkers for glycaemic deterioration in type 2 diabetes
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
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| 23. |
- Slieker, Roderick C, et al.
(författare)
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Replication and cross-validation of type 2 diabetes subtypes based on clinical variables : an IMI-RHAPSODY study
- 2021
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64:9, s. 1982-1989
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate and cross-validate these type 2 diabetes clusters in three large cohorts using variables readily measured in the clinic. Methods: In three independent cohorts, in total 15,940 individuals were clustered based on age, BMI, HbA1c, random or fasting C-peptide, and HDL-cholesterol. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort’s cluster centres. Finally, we compared the time to insulin requirement for each cluster. Results: Five distinct type 2 diabetes clusters were identified and mapped back to the original four All New Diabetics in Scania (ANDIS) clusters. Using C-peptide and HDL-cholesterol instead of HOMA2-B and HOMA2-IR, three of the clusters mapped with high sensitivity (80.6–90.7%) to the previously identified severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) clusters. The previously described ANDIS mild age-related diabetes (MARD) cluster could be mapped to the two milder groups in our study: one characterised by high HDL-cholesterol (mild diabetes with high HDL-cholesterol [MDH] cluster), and the other not having any extreme characteristic (mild diabetes [MD]). When these two milder groups were combined, they mapped well to the previously labelled MARD cluster (sensitivity 79.1%). In the cross-validation between cohorts, particularly the SIDD and MDH clusters cross-validated well, with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity, ranging from 36.1% to 92.3%, where individuals shifted from SIRD to MD and vice versa. People belonging to the SIDD cluster showed the fastest progression towards insulin requirement, while the MDH cluster showed the slowest progression. Conclusions/interpretation: Clusters based on C-peptide instead of HOMA2 measures resemble those based on HOMA2 measures, especially for SIDD, SIRD and MOD. By adding HDL-cholesterol, the MARD cluster based upon HOMA2 measures resulted in the current clustering into two clusters, with one cluster having high HDL levels. Cross-validation between cohorts showed generally a good resemblance between cohorts. Together, our results show that the clustering based on clinical variables readily measured in the clinic (age, HbA1c, HDL-cholesterol, BMI and C-peptide) results in informative clusters that are representative of the original ANDIS clusters and stable across cohorts. Adding HDL-cholesterol to the clustering resulted in the identification of a cluster with very slow glycaemic deterioration. Graphical abstract: [Figure not available: see fulltext.]
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| 24. |
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| 25. |
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| 26. |
- Venugopalan, Shankar R., et al.
(författare)
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Novel expression and transcriptional regulation of FoxJ1 during oro-facial morphogenesis
- 2008
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 17:23, s. 3643-3654
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Tidskriftsartikel (refereegranskat)abstract
- Axenfeld-Rieger syndrome (ARS) patients with PITX2 point mutations exhibit a wide range of clinical features including mild craniofacial dysmorphism and dental anomalies. Identifying new PITX2 targets and transcriptional mechanisms are important to understand the molecular basis of these anomalies. Chromatin immunoprecipitation assays demonstrate PITX2 binding to the FoxJ1 promoter and PITX2C transgenic mouse fibroblasts and PITX2-transfected cells have increased endogenous FoxJ1 expression. FoxJ1 is expressed at embryonic day 14.5 (E14.5) in early tooth germs, then down-regulated from E15.5-E17.5 and re-expressed in the inner enamel epithelium, oral epithelium, tongue epithelium, sub-mandibular salivary gland and hair follicles during E18.5 and neonate day 1. FoxJ1 and Pitx2 exhibit overlapping expression patterns in the dental and oral epithelium. PITX2 activates the FoxJ1 promoter and, Lef-1 and beta-catenin interact with PITX2 to synergistically regulate the FoxJ1 promoter. FoxJ1 physically interacts with the PITX2 homeodomain to synergistically regulate FoxJ1, providing a positive feedback mechanism for FoxJ1 expression. Furthermore, FoxJ1, PITX2, Lef-1 and beta-catenin act in concert to activate the FoxJ1 promoter. The PITX2 T68P ARS mutant protein physically interacts with FoxJ1; however, it cannot activate the FoxJ1 promoter. These data indicate a mechanism for the activity of the ARS mutant proteins in specific cell types and provides a basis for craniofacial/ tooth anomalies observed in these patients. These data reveal novel transcriptional mechanisms of FoxJ1 and demonstrate a new role of FoxJ1 in oro-facial morphogenesis.
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| 27. |
- Åkerlund, Andreas, 1977-, et al.
(författare)
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Akademiskt utbyte och internationell migration : En studie av stipendiater inom Svenska institutets stipendieprogram 1997-2015
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Akademisk mobilitet är en aspekt av internationell migration, som sällan får samma uppmärksamhet som flykt eller arbetskraftsmigration. Denna mobilitet möjliggörs ofta genom stipendier, och i Sverige är Svenska institutet en av de viktigaste stipendiegivarna. Föreliggande rapport handlar om personer som fått ett mobilitetsstipendium inom Visbyprogrammet. Programmet har funnits sedan 1997 och är inriktat mot länder i östra Europa. Ur ett migrationsperspektiv är dessa stipendiater en intressant grupp vad gäller migrationsmönster och internationella nätverk.Stipendieutdelning är en av många faktorer som är med och formar internationella migrationsflöden. Det innebär att de regler som svenska staten ställer upp för sina stipendier i kombination med Svenska institutets praktiska hantering av samma stipendier påverkar migrationen, då de gör internationell akademisk mobilitet möjlig för vissa specifika grupper. Över tid har Visbyprogrammet gått från att ha en näringslivsfrämjande, biståndspolitisk och tillväxtskapande inriktning till att handla om regionalt samarbete, avspänning och social utveckling. Programmet tillhör alltså tre politikområden, nämligen a) bistånds- och utvecklingsarbete, b) internationaliseringen av den högre utbildningen och c) offentlig diplomati, främjandet av Sverige och svensk ekonomi.Inom existerande forskning är det mycket ovanligt att ovan nämnda politikområden relateras till varandra. Studiens utgångspunkt är dock att relationen dem emellan är grundläggande för att förstå Visbyprogrammet. Utifrån detta antagande undersöks fem olika områden. Först och främst i vilken utsträckning stipendiaterna utgör en viktig resurs för ekonomin, politiken eller forskningen i sina hemländer (1), i vilken mån stipendiaterna fortfarande är förbundna med Sverige och det svenska samhället eller till och med är bosatta i Sverige och verksamma på svensk arbetsmarknad (2), samt om stipendiaterna flyttat vidare till andra länder och en internationell arbetsmarknad (3). Därutöver undersöks även i vilken utsträckning stipendierna skapar ett utbildningskapital, ett språkligt kapital och ett svenskt symboliskt kapital (4), samt hur stipendiaterna själva värderar sin stipendievistelse och de primäramotiven för att söka sig till Sverige (5).Som underlag för den aktuella studien genomfördes en enkätundersökning med tidigarelångtidsstipendiater inom Visbyprogrammet. Enkäten innehöll 34 frågor ochbesvarades av total 482 personer. Huvudresultaten är att stipendiatsgruppen harförändrats mellan 1997 och 2015. Från att initialt ha kommit från Baltikum, Polenoch Ryssland, kommer dagens stipendiater företrädelsevis från Ukraina, Rysslandoch Vitryssland. Dessutom har stipendiaternas ämnesinriktning förskjutits frånteknik och naturvetenskap mot samhällsvetenskap och humaniora. Orsaken tilldetta är att ekonomi och tillväxt tonats ned inom Visbyprogrammet till förmånför säkerhetspolitik och bistånd. Ett politiskt formulerat stipendieprogram som Visbyprogrammet och en mediär som Svenska institutet, har därmed en stor betydelseför hur den internationella student- och forskarmobiliteten ser ut och hur den varierar över tid.Ett annat centralt resultat är att stipendieperioden öppnar upp för tre olika livsbanor. Majoriteten av respondenterna flyttade tillbaka till sina hemländer (50 procent)medan mer än en på fyra (27 procent) bodde kvar i Sverige. En nästan lika stor grupp (23 procent) bosatte sig istället i ett tredje land, vanligtvis ett västeuropeiskt land eller USA. Samma mönster syns även om man ser till de länder där respondenterna bott en kortare period efter stipendieperioden. En vistelse i Sverige genererar alltså utbildningskapital som även har ett värde i andra länder. Visbystipendierna fungerar som en viktig del i en såväl socialt uppåtstigande som geografisk mobilitetsrörelse.Den främsta pullfaktorn för att söka sig till just Sverige var dock existensen av stipendierna och den ekonomiska säkerhet de innebär. En övervägande majoritet av stipendiaterna uppskattar att tiden i Sverige har haft en avgörandebetydelse för deras vidare karriär, men också att de har kunnat etablera stabila kontakter mellan Sverige och ursprungslandet.
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| 28. |
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| 29. |
- Åkerlund, Mikael
(författare)
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Gene expression studies of pregastrulation development: the basement membrane is essential for cell differentiation
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Basement membranes (BMs) are sheet-like structures of extracellular matrix. They act as a supporting structure but can also significantly influence cellular behavior in development, tissue homeostasis and disease. Laminins, a major BM component, are multidomain proteins, consisting of three polypeptide chains (α, β and γ). During pregastrulation development, stem cells convert and epithelial tissues are formed. This process is faithfully mimicked in vitro by embryoid body (EB) cultures. Fibroblast growth factor (FGF) signaling is crucial when the step-like process of EB development is initiated with the formation of an endoderm. A subendodermal BM is formed, in which the globular domains LG4-5 of the laminin α1 chain (α1LG4-5) are responsible for the induction of the epiblast EBs derived form embryonic stem (ES) cells, modified to repress FGF receptor signaling, have been described before. However, a full-scale analysis of the transcriptome was missing. We therefore analysed these EBs at four time points during differentiation by the use of microarray technique. An extensive catalogue of affected genes was reported. A majority of the genes directed by FGF signalling were encoding BM and endodermal proteins. In addition, we also analysed the expression profile of wild type EBs. In both these studies, we found interesting genes not previously described in early development or identified as FGF targets. Hopefully, our gene catalogue will be a valuable source for the scientific community interested in FGF signaling, developmental biology and stem cell research. Furthermore, a gene expression study was set up to get a better insight of epiblast inducement by α1LG4-5. EBs derived form ES cells with a targeted deletion of the α1LG4-5 domains were analysed. To our surprise, we found several indications of an incomplete differentiation of the visceral endoderm. We therefore hypothesize a novel autocrine mechanism for α1LG4-5 in regulating the developing endoderm. We also suggest novel roles for laminin LG4-5 in the neuromuscular system. Using laminin α2 chain deficient mice overexpressing laminin α1 chain lacking the LG4-5 domains, we show that these domains, and consequently binding to the receptor dystroglycan are not crucial in diaphragm and heart, but essential in the peripheral nervous system.
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| 30. |
- Åkerlund, Mikael, et al.
(författare)
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Laminin alpha1 domains LG4-5 are essential for the complete differentiation of visceral endoderm.
- 2009
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 338:1, s. 129-137
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Tidskriftsartikel (refereegranskat)abstract
- The heterotrimeric basement membrane protein laminin-111 is essential for early mouse embryogenesis. Its beta1 and gamma1 chains are crucial for endoderm differentiation and for the formation of basement membranes, whereas alpha1 chain null mice only lack the extraembryonic Reichert's membrane. Nevertheless, mice deficient in the cell-binding alpha1 globular domains 4-5 (LG4-5) have a more severe phenotype than animals devoid of the whole alpha1 chain, as these domains are required for the formation of a polarized ectoderm. However, the influence of the alpha1LG4-5 domains on endoderm differentiation is unclear. We have used microarray analysis to compare the expression profiles of normal and alpha1LG4-5-deficient embryoid bodies and show that genes encoding secreted plasma proteins and proteins involved in endocytosis are reduced in alpha1LG4-5-deficient embryoid bodies, indicating incomplete differentiation of the visceral endoderm. Moreover, mice lacking alpha1LG4-5 display endoderm disorganization and a defective expression of the endoderm marker Dab2. We hypothesize that alpha1LG4-5 domains provide an autocrine signal necessary for the complete differentiation of a functional visceral endoderm and vital signals for the polarization of the epiblast.
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