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1.
  • Porras Hernandez, Ana Maria, et al. (författare)
  • A simplified approach to control cell adherence on biologically derived in vitro cell culture scaffolds by direct UV-mediated RGD linkage
  • 2020
  • Ingår i: Journal of materials science. Materials in medicine. - : Springer Nature. - 0957-4530 .- 1573-4838. ; 31:10
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, we present a method to fabricate a hyaluronic acid hydrogel with spatially controlled cell-adhesion properties based on photo-polymerisation cross-linking and functionalisation. The approach utilises the same reaction pathway for both steps meaning that it is user-friendly and allows for adaptation at any stage during the fabrication process. Moreover, the process does not require any additional cross-linkers. The hydrogel is formed by UV initiated radical addition reaction between acrylamide groups on the hyaluronic acid backbone. Cell adhesion is modulated by functionalising the adhesion peptide sequence RGD (arginine-glycine-aspartate) onto the hydrogel surface via radical mediated thiol-ene reaction using the non-reacted acrylamide groups. We show that 10 x 10 µm2 squares could be patterned with sharp features and a good resolution. The smallest area that could be patterned resulting in good cell adhesion was 25 x 25 µm2 squares, showing single-cell adhesion. Mouse brain endothelial cells adhered and remained in culture for up to 7 days on 100 x 100 µm2 square patterns. We see potential for this material combination for future use in novel organ-on-chip models and tissue engineering where the location of the cells is of importance and to further study endothelial cell biology.
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2.
  • Allentoft, Morten E., et al. (författare)
  • Population genomics of post-glacial western Eurasia
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
  • Tidskriftsartikel (refereegranskat)abstract
    • Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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4.
  • Duarte, Ana I., et al. (författare)
  • Dual Therapy with Liraglutide and Ghrelin Promotes Brain and Peripheral Energy Metabolism in the R6/2 Mouse Model of Huntington's Disease
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuronal loss alongside altered energy metabolism, are key features of Huntington's disease (HD) pathology. The orexigenic gut-peptide hormone ghrelin is known to stimulate appetite and affect whole body energy metabolism. Liraglutide is an efficient anti-type 2 diabetes incretin drug, with neuroprotective effects alongside anorectic properties. Combining liraglutide with the orexigenic peptide ghrelin may potentially promote brain/cognitive function in HD. The R6/2 mouse model of HD exhibits progressive central pathology, weight loss, deranged glucose metabolism, skeletal muscle atrophy and altered body composition. In this study, we targeted energy metabolism in R6/2 mice using a co-administration of liraglutide and ghrelin. We investigated their effect on brain cortical hormone-mediated intracellular signalling pathways, metabolic and apoptotic markers, and the impact on motor function in HD. We here demonstrate that liraglutide, alone or together with ghrelin (subcutaneous daily injections of 150 μg/kg (ghrelin) and 0.2 mg/kg (liraglutide), for 2 weeks), normalized glucose homeostatic features in the R6/2 mouse, without substantially affecting body weight or body composition. Liraglutide alone decreased brain cortical active GLP-1 and IGF-1 levels in R6/2 mice, alongside higher ADP levels. Liraglutide plus ghrelin decreased brain insulin, lactate, AMP and cholesterol levels in R6/2 mice. Taken together, our findings encourage further studies targeting energy metabolism in HD.
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6.
  • Nettleton, Jennifer A, et al. (författare)
  • Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry
  • 2015
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 24:16, s. 4728-4738
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
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7.
  • Olsson, Bengt, et al. (författare)
  • A decision support model for individual tree stump harvesting options based on criteria for economic return and environmental protection
  • 2017
  • Ingår i: Scandinavian Journal of Forest Research. - : Taylor & Francis Group. - 0282-7581 .- 1651-1891. ; 32, s. 246-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Based on principles of multi-criteria analysis techniques, a model (MAPStump-E) for decision support on stump harvesting at stand level was developed. The model applies the concept that each stump can be attributed production values (economic) and environmental values (here soil protection and water quality). Individual tree stump information was incorporated directly from the production reports of harvesters and combined with high-resolution Geographical Information System data on topography and soil type to create a production submodel and a soil and water vulnerability submodel (SWM). To test the model, it was applied to a 45-ha study forest in south-central Sweden and the outcome of nine scenarios with varying bioenergy prices and environmental protection levels was examined. Combined analysis of the effects of production and environmental criteria on total dry mass of harvestable stumps at the study site showed that biomass prices had a stronger influence than environmental criteria. Conflict stumps were defined as stumps suitable for harvest based on production criteria, but unsuitable based on soil and water protection criteria. In a ?medium? price scenario, the proportion of conflict stumps at the study site ranged from 6% to 18%, depending on protection level set.
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8.
  • Padmanabhan, Sandosh, et al. (författare)
  • Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
  • 2010
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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10.
  • Porras, Ana Maria, et al. (författare)
  • Photopatterning of hyaluronic acid hydrogels for cell culture scaffolds
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • Organs-on-chips technologies require the development of micro engineered devices to represent functional units of human organs. These devices use cell culture scaffolds to give support and structure for the cultured cells. Hydrogels are attractive scaffold materials, due to their high water content and because they are derived from natural polymers found in the extracellular matrix of different tissues in the human body. Hyaluronic acid can form hydrogels when functionalized with chemo-selective groups. These chemically cross-linked hydrogels can be modified with adhesion motifs, such as RGD peptides, to increase their biocompatibility and promote cell adhesion. In this work we use a photolithographic method to pattern the RGD peptide into distinct areas of the hyaluronic acid hydrogel with the aim to spatially control the cell attachment on the HA hydrogel scaffolds
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12.
  • Sjögren, Jonathan, et al. (författare)
  • EndoS and EndoS2 hydrolyze Fc-glycans on therapeutic antibodies with different glycoform selectivity and can be used for rapid quantification of high-mannose glycans.
  • 2015
  • Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 25:10, s. 1053-1063
  • Tidskriftsartikel (refereegranskat)abstract
    • Enzymes that affect glycoproteins of the human immune system, and thereby modulate defense responses, are abundant among bacterial pathogens. Two endoglycosidases from the human pathogen Streptococcus pyogenes, EndoS and EndoS2, have recently been shown to hydrolyze N-linked glycans of human IgG. However, detailed characterization and comparison of the hydrolyzing activities have not been performed. In the present study we set out to characterize the enzymes by comparing the activities of EndoS and EndoS2 on a selection of therapeutic monoclonal antibodies (mAbs), cetuximab, adalimumab, panitumumab, and denosumab. By analyzing the glycans hydrolyzed by EndoS and EndoS2 from the antibodies using MALDI-TOF, we found that both enzymes cleaved complex glycans, and that EndoS2 hydrolyzed hybrid and oligomannose structures to a greater extent compared to EndoS. A comparison of UHPLC profiles of the glycan pool of cetuximab hydrolyzed with EndoS and EndoS2 showed that EndoS2 hydrolyzed hybrid and oligomannose glycans whereas these peaks were missing in the EndoS chromatogram. We utilized this difference in glycoform selectivity and developed a liquid chromatography separation method to quantify high-mannose content in the Fc fragments of the selected mAbs. We conclude that EndoS and EndoS2 hydrolyze different glycoforms from the Fc-glycosylation site on therapeutic mAbs, and that this can be used for rapid quantification of high-mannose content.
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13.
  • Allentoft, Morten E., et al. (författare)
  • 100 ancient genomes show repeated population turnovers in Neolithic Denmark
  • 2024
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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14.
  • André, Maria, et al. (författare)
  • Effects of pretreatments and hydrothermal aging on biaxial flexural strength of lithium di-silicate and Mg-PSZ ceramics
  • 2016
  • Ingår i: Journal of Dentistry. - : Elsevier BV. - 0300-5712 .- 1879-176X. ; 55, s. 25-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the effect of specimen thickness, pretreatment and hydrothermal aging on the biaxial flexural strength (BFS) of lithium di-silicate glass (e.max Cad) and magnesia-stabilized zirconia (ZirMagnum) ceramic discs. Methods: The e.max Cad discs was studied: i) crystallized, ii) crystallized and glazed and iii) crystallized, glazed and unglazed side etched with hydrofluoric acid. The ZirMagnum discs were studied: i) as delivered, ii) after sandblasting and iii) after heat treatment similar to veneering. Hydrothermal aging was simulated by autoclave treatment. Results: The BFS of all the ZirMagnum specimens was superior (p < 0.001) to all the e.max Cad specimens. Glazing the 0.4 mm e.max Cad discs reduced (p < 0.05) their BFS compared with the unglazed 0.8 mm specimens, whereas glazing of 0.8 mm discs had no influence (p > 0.05) on the strength. Etching and autoclaving of e.max Cad did not affect (p > 0.05) the BFS. For ZirMagnum sandblasting with 0.2 MPa or 0.6 MPa did not influence the biaxial flexural strength (p > 0.05), whereas heat treatment reduced (p < 0.01) the BFS of 0.6 MPa sandblasted ZirMagnum. Autoclaving reduced the strength (p < 0.05) compared with ZirMagnum as delivered, whereas autoclaving of the 0.6 MPa sandblasted and heat treated specimens did not influence (p > 0.05) the BFS. Glazing, etching and sandblasting increased (p < 0.05) surface roughness. Conclusions: The effects of glazing, heat treatment, aging and mechanical treatment of the materials evaluated should be considered since their strength could be affected. Clinical significance: Mechanical properties of restorations made from prefabricated ceramic blocks could be affected of various treatments and could change over time.
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15.
  • Arvaniti, Maria, et al. (författare)
  • Temptation in consumption and optimal taxation
  • 2023
  • Ingår i: Journal of Economic Behavior and Organization. - : Elsevier. - 0167-2681 .- 1879-1751. ; 205, s. 687-707
  • Tidskriftsartikel (refereegranskat)abstract
    • This article aims to integrate temptation preferences into the theory of optimal taxation with heterogenous agents and asymmetric information. Consumers are tempted to over-consume a commodity which may lead to an over-supply of labor. Resisting this temptation implies a utility cost and any policy that reduces this cost is welfare improving. We uncover novel channels for government intervention and the interaction between the welfare improving and redistributive roles of public policy. We also identify a commitment mechanism that works through the endogenous labor choice and affects the design and effectiveness of the optimal tax policy.
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16.
  • Axelsson, Viktoria, et al. (författare)
  • Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells.
  • 2006
  • Ingår i: Biochem Biophys Res Commun. - 0006-291X. ; 345:3, s. 1068-74
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, a significant increase by 50% in intracellular free calcium concentration ([Ca(2+)](i)) was observed in differentiated human neuroblastoma (SH-SY5Y) cells after exposure to 0.25microM of the fungal metabolite gliotoxin for 72h. Further, the involvement of caspases and calpains was demonstrated to underlie the gliotoxin-induced cytotoxic and neurite degenerative effects. The caspase inhibitor Z-VAD-fmk almost completely reduced the neurite degeneration from 40% degeneration of neurites to 5% as compared to control. Inhibition of calpains with calpeptin significantly attenuated gliotoxin-induced cytotoxicity, determined as reduction in total cellular protein content, from 43% to 14% as compared to control cells. Western blot analyses of alphaII-spectrin breakdown fragments confirmed activity of the proteases, and that alphaII-spectrin was cleaved by caspases in gliotoxin-exposed cells. These results show that calpains and caspases have a role in the toxicity of gliotoxin in differentiated SH-SY5Y cells and that the process may be Ca(2+)-mediated.
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17.
  • B. Wrammerfors, E. Tobias, et al. (författare)
  • Exploratory neutron tomography of articular cartilage
  • Ingår i: Osteoarthritis and Cartilage. - 1063-4584.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate the feasibility of using neutron tomography to gain new knowledge of human articular cartilage degeneration in osteoarthritis (OA). Different sample preparation techniques were evaluated to identify maximum intra-tissue contrast. Design: Human articular cartilage samples from 14 deceased donors (18–75 years, 9 males, 5 females) and 4 patients undergoing total knee replacement due to known OA (all female, 61–75 years) were prepared using different techniques: control in saline, treated with heavy water saline, fixed and treated in heavy water saline, and fixed and dehydrated with ethanol. Neutron tomographic imaging (isotropic voxel sizes from 7.5 to 13.5 µm) was performed at two large scale facilities. The 3D images were evaluated for gradients in hydrogen attenuation as well as compared to images from absorption X-ray tomography, magnetic resonance imaging, and histology. Results: Cartilage was distinguishable from background and other tissues in neutron tomographs. Intra-tissue contrast was highest in heavy water-treated samples, which showed a clear gradient from the cartilage surface to the bone interface. Increased neutron flux or exposure time improved image quality but did not affect the ability to detect gradients. Samples from older donors showed high variation in gradient profile, especially from donors with known OA. Conclusions: Neutron tomography is a viable technique for specialized studies of cartilage, particularly for quantifying properties relating to the hydrogen density of the tissue matrix or water movement in the tissue.
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18.
  • Bengtsson, Göran, et al. (författare)
  • Statistical analysis of the influence of conspecifics on the dispersal of a soil collembola.
  • 2002
  • Ingår i: Theoretical Population Biology. - : Elsevier BV. - 1096-0325 .- 0040-5809. ; 61:2, s. 97-113
  • Tidskriftsartikel (refereegranskat)abstract
    • The evidence for dispersal activity among soil-living invertebrates comes mainly from observations of their movement on artificial substrates or of colonisation of defaunated soils in the field. In an attempt to elucidate the dispersal pattern of soil collembolans in the presence of conspecifics, statistical analyses were undertaken to describe and simulate the movement of groups of Onychiurus armatus released in trays of homogeneous soil. A chi(2) test was used to reject the null hypothesis that individuals moved independently of each other and uniformly in all directions. The mean radial distance moved (1-2 cm day(-1)) and the radial standard deviation varied temporally and with the density of conspecifics. To capture the interaction between the moving individuals, four dispersal models (pure diffusion, diffusion with drift interaction, drift interaction and synchronised diffusion, and drift interaction and behavioural mood), were formulated as stochastic differential equations. The parameters of the models were estimated by minimising the deviance between the observed replicates and replicates that were simulated using the models. The dynamics of movement were best described by modelling the drift interaction as dependent on whether individuals were in a social or an asocial mood.
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19.
  • Berghof, Maria, et al. (författare)
  • Inversion of droplet aerosol analyzer data for long-term aerosol-cloud interaction measurements
  • 2014
  • Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 7:4, s. 877-886
  • Tidskriftsartikel (refereegranskat)abstract
    • The droplet aerosol analyzer (DAA) was developed to study the influence of aerosol properties on clouds. It measures the ambient particle size of individual droplets and interstitial particles, the size of the dry (residual) particles after the evaporation of water vapor and the number concentration of the dry (residual) particles. A method was developed for the evaluation of DAA data to obtain the three-parameter data set: ambient particle diameter, dry (residual) particle diameter and number concentration. First results from in-cloud measurements performed on the summit of Mt. Brocken in Germany are presented. Various aspects of the cloud-aerosol data set are presented, such as the number concentration of interstitial particles and cloud droplets, the dry residue particle size distribution, droplet size distributions, scavenging ratios due to cloud droplet formation and size-dependent solute concentrations. This data set makes it possible to study clouds and the influence of the aerosol population on clouds.
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20.
  • Borglin, Gunilla, et al. (författare)
  • Registered nurse's experiences of continence care for older people : A qualitative descriptive study
  • 2020
  • Ingår i: International Journal of Older People Nursing. - : John Wiley & Sons. - 1748-3735 .- 1748-3743. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: This study aimed to illuminate nurses’ experience of continence care for older people receiving home care, either in their own home or in an assisted living facility. Background: Registered Nurses (RNs) have a major role to play in identifying and establishing appropriate actions regarding continence care for older people. However, the crucial nursing care pathway for continence care is commonly described as poor. Methods: Interviews were conducted with 11 RNs providing home care, and the transcribed texts were analysed using inductive content analysis. Result The impressions of RNs were categorised according to four themes: perceptions of continence care, an open approach to continence care, the need for personalised aid fittings and the importance of teamwork in continence care. Key findings were the importance of teamwork; the need for nurses to embrace leadership at the point of care and be more visible in terms of the provision of direct care; substantiation that evidence‐based interventions, such as scheduled toileting and prompted voiding, should constitute the norm in continence care within the context of home care; and the need for nurses to support the right of older persons to receive an assessment of their continence problems, deemed to be the minimum standard of quality care. Conclusion: The provision of continence care that is based on key nursing standards, such as evidence‐based and person‐centred care, as well as individualised continence care that is based on evidenced‐based guidelines, would ensure an improvement in the continence care that is presently on offer to older people.
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21.
  • Borgström, Maria, 1951- (författare)
  • Att vara mitt emellan : hur spanskamerikanska ungdomar i Sverige kan uppfatta villkoren för sin sociokulturella identitetsutveckling
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This study aims to elucidate the conditions for the socio-cultural identity development of Latin American youths living in Sweden. It has been conducted with a view to the youths' own perspective, what they consider important about the significant contexts in which they have grown up and how they looked upon themselves during this process.I examine socio-cultural identity from three aspects: identity, language and culture. The term socio-cultural is a combination of a social and a cultural concept. The study is retroductive: my analysis and interpretation of how the youths look at their life situation build on data collected during their intermediate years in compulsory school (grades four to six) and upper secondary school. The research method is based on a life history approach. The data come from interviews and group discussions with the youths, questionnaire to teachers and the youths, drawings by the youths, informal discussions with parents and teachers, correspondence, and my own journal notes. Symbolic interaction and ethnology have provided the theoretical framework and central concepts of the study. These theoretical concepts, along with the youths' own concepts, serve both as guidelines and tools for the analysis and interpretation.The youths participate actively in the formulation of their socio-cultural identity. Identity develops through interaction with others, which is why social relationships are of central importance. A sense of security or insecurity develops as a result of these processes. Language is the mediating activity that is present throughout the whole process. Furthermore, the results show that school is not a place where the youths feel secure and that how they are received in school is of vital importance. The youths find security within their extended families, even if their parents are divorced.Growing up in Rinkeby gives the youths in the study a sense of security. In Rinkeby they do not stand out as being different. But the youths are also aware that to be accepted by the Swedish society they must conceal the fact that they come from Rinkeby.The young people identify either with their own group (Chileans) and their own language (Spanish), or with the "immigrant group" and its language (Rinkeby Swedish). Sometimes they identify with both, but never with "the Swedes". They switch linguistic codes (Spanish and Swedish) when talking among themselves: that and Rinkeby Swedish are identity markers. Most of the youths consider themselves to be "between two worlds": neither the family nor society understands their situation. They experience that however much they may wish to, they are not allowed to belong to the Swedish society. Some feel more integrated than others, and some have a sense of identity and know where they stand in relation to the groups around them. Others continue their search for identity.
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22.
  • Brittberg, Mats, 1953, et al. (författare)
  • Clonal growth of human articular cartilage and the functional role of the periosteum in chondrogenesis.
  • 2005
  • Ingår i: Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. - : Elsevier BV. - 1063-4584. ; 13:2, s. 146-53
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Clinical cartilage repair with transplantation of cultured chondrocytes, the first described technique introduced in 1994, includes a periosteal membrane but today cells are also implanted without the periosteal combination. The aim of this study was to see if the periosteum had more than a biomechanical function and if the periosteum had a biological effect on the seeded cells tested in an agarose system in which the clonal growth in agarose and the external growth stimulation could be analysed. METHODS: Four different experiments were used to study the growth of human chondrocytes in agarose and the periosteal influence. Human chondrocytes were isolated and transferred to either primary or secondary agarose culture. After 4 weeks, the total number of clones >50 microm was counted. Cocultures of chondrocytes and periosteal tissue, cultures of chondrocytes with conditioned medium from chondrocytes, periosteal cells and fibroblast were used to study a potential stimulatory effect on growth and different cytokines and growth factors were analysed. RESULTS: It was found that the human chondrocytes had different growth properties in agarose with the formation of four different types of clones: a homogenous clone without matrix production, a homogenous clone with matrix production, a differentiated clone with matrix production and finally a differentiated clone without matrix production. The periosteum exerted a paracrine effect on cultured chondrocytes in agarose resulting in a higher degree of cloning. The chondrocytes produced significant amounts of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta. The periosteum produced significant amounts of IL-6, IL-8 and TGF-beta. Cocultures of chondrocytes and periosteum demonstrated a potentiation of IL-6 and IL-8 release but not of TGF-beta and GM-CSF. CONCLUSION: Articular chondrocytes are able to form clones of different properties in agarose and the periosteum has a capacity of stimulating chondrocyte clonal growth and differentiation and secretes significant amounts of IL-6, IL-8, GM-CSF and TGF-beta. It may be that the repair of cartilage defects with seeded chondrocytes could benefit from the combination with a periosteal graft. The production of TGF-beta by implanted chondrocytes could influence the chondrogenic cells in the periosteum to start a periosteal chondrogenesis and together with the matrix from implanted chondrocyte production, a repair of cartilaginous appearance may develop; a dual chondrogenic response is possible.
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23.
  • Bygdell, Maria, et al. (författare)
  • Prevalence of overweight and obesity from 5 to 19 years of age in Gothenburg, Sweden
  • 2021
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 110:12, s. 3349-3355
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim The aim of this study was to present prevalence data for overweight and obesity across school age in a large, recent, population-based cohort of children in Gothenburg, Sweden. Methods We included 66,807 children (48.5% girls) aged 5-18.9 years who had their height and weight measured in school health care 2015-2018. The BMI values were categorised according to the age-dependent cut-offs for overweight and obesity from the International Obesity Task Force (IOTF). Results Overall, the prevalence of overweight and obesity for girls and boys was 18.1% and 18.0%, respectively. We observed increasing proportions of overweight (girls 11.5-17.1% and boys 8.4-17.4%) and obesity (girls 3.0-4.2% and boys 2.7-6.1%) with increasing age (p < 0.001 for trend in both sexes). Moreover, girls had higher prevalence of overweight during ages 5.0 to 8.9 years compared with boys (p < 0.001), while boys had higher prevalence of obesity 15.0-18.9 years compared with girls (p < 0.001). Conclusion In conclusion, we demonstrate increasing prevalence of overweight and obesity across the entire school age range, as well as differences in prevalences between boys and girls, in a population-based sample of 67,000 children in Gothenburg city, Sweden. Continuous monitoring of schoolchildren, together with effective preventive measures, is crucial to curb the obesity epidemic and its consequences.
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24.
  • Bäck, Maria, et al. (författare)
  • Home-based supervised exercise versus hospital-based supervised exercise or unsupervised walk advice as treatment for intermittent claudication : a systematic review.
  • 2015
  • Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 47:9, s. 801-808
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To evaluate the effects of home-based supervised exercise vs hospital-based supervised exercise, and the effects of home-based supervised exercise vs unsupervised "go home and walk advice" on daily life and corridor-walking capacity, health-related quality of life and patient-reported functional walking capacity in patients with intermittent claudication.DATA SOURCES: Systematic literature searches were conducted in PubMed, EMBASE, ProQuest, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), the Cochrane Library, and a number of Health Technology Assessment (HTA)-databases in October 2014.STUDY SELECTION: Randomized controlled trials and non-randomized controlled trials (> 100 patients) were considered for inclusion.DATA EXTRACTION: Data extraction and risk of bias assessment was performed independently and discussed in meetings.DATA SYNTHESIS: Seven randomized controlled trials and 2 non-randomized controlled studies fulfilled the inclusion criteria. The included studies had some, or major, limitations.CONCLUSION: Based on a low quality of evidence, home-based supervised exercise may lead to less improvement in maximum and pain-free walking distance, and in more improvement in daily life walking capacity, compared with hospital-based supervised exercise. Home-based supervised exercise may improve maximum and pain-free walking distance compared with "go home and walk advice" and result in little or no difference in health-related quality of life and functional walking capacity compared with hospital-based supervised exercise or "go home and walk advice". Further research is needed to establish the optimal exercise modality for these patients.
  •  
25.
  • Bäck, Maria, 1978, et al. (författare)
  • Home-based versus hospital-based supervised exercise or walk advice as treatment for intermittent claudication : Hembaserad jämfört med sjukhusbaserad handledd fysisk träning eller träningsråd som behandling vid claudicatio intermittens
  • 2014
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Method and patient group Intermittent claudication, the most common symptomatic presentation of peripheral arterial disease, is present in 7% of Swedish people aged 60 years or older. The progressive atherosclerotic process involves the development of stenoses and/or occlusions in the arteries propagating blood to the lower limbs. This causes effort-induced pain in the affected limb(s). Treatment is usually conservative and includes exercise therapy. Today, current practice in Sweden for patients with IC usually does not include hospital-based supervised exercise programs. A home-based supervised exercise program in a self-chosen environment might bridge the gap between the highly structured and costly hospital-based supervised exercise programs and ’go home and walk advice’. Question at issue Is home-based supervised exercise more effective than either unsupervised ‘go home and walk advice’, or hospital-based supervised exercise, for patients with intermittent claudication, in terms of walking distance, health related quality of life, symptoms, and risks associated with exercise? Studied risks and benefits for patients Ten articles were identified: two systematic reviews, six randomized controlled trials (RCT) and two cohort studies. The systematic reviews were only commented on. The quality of evidence (GRADE ⊕⊕) was low for all conclusions. Concluding remark Home-based supervised exercise for patients with intermittent claudication was compared with hospitalbased supervised exercise, or ‘go home and walk advice’. Six RCTs and two cohort studies were identified. There is low quality of evidence (GRADE ⊕⊕) that home-based supervised exercise, as compared with ‘go home and walk advice’, may slightly improve maximum and pain-free walking distance and result in little or no difference in health-related quality of life, and functional walking ability. There is low quality of evidence (GRADE ⊕⊕) that home-based supervised exercise may lead to less improvement in both maximum and pain-free walking distance than supervised hospital-based exercise, and result in little or no difference in health-related quality of life, and functional walking ability. There are no major ethical issues, and a reliable estimate of the total cost change is not possible, due to a total lack of reliable long-term data.
  •  
26.
  • Chambers, John C., et al. (författare)
  • Genetic loci influencing kidney function and chronic kidney disease
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 373-375
  • Tidskriftsartikel (refereegranskat)abstract
    • Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.
  •  
27.
  • Colldén, Hannah, et al. (författare)
  • The gut microbiota is a major regulator of androgen metabolism in intestinal contents.
  • 2019
  • Ingår i: American journal of physiology. Endocrinology and metabolism. - 1522-1555. ; 317:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Androgens exert important effects both in androgen-responsive tissues and in the intestinal tract. To determine the impact of the gut microbiota (GM) on intestinal androgen metabolism, we measured unconjugated (free) and glucuronidated androgen levels in intestinal contents from the small intestine, with a low bacterial density, and from cecum and colon, with a high bacterial density. Using a specific, sensitive gas chromatography-tandem mass spectrometry method, we detected high levels of glucuronidated testosterone (T) and dihydrotestosterone (DHT) in small intestinal content of mice of both sexes, whereas in the distal intestine we observed remarkably high levels of free DHT, exceeding serum levels by >20-fold. Similarly, in young adult men high levels of unconjugated DHT, >70-fold higher than in serum, were detected in feces. In contrast to mice with a normal GM composition, germ-free mice had high levels of glucuronidated T and DHT, but very low free DHT levels, in the distal intestine. These findings demonstrate that the GM is involved in intestinal metabolism and deglucuronidation of DHT and T, resulting in extremely high free levels of the most potent androgen, DHT, in the colonic content of young and healthy mice and men.
  •  
28.
  • Dahlman, Ingrid, et al. (författare)
  • A unique role of monocyte chemoattractant protein 1 among chemokines in adipose tissue of obese subjects
  • 2005
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 90:10, s. 5834-5840
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Low-grade inflammation in adipose tissue may contribute to insulin resistance in obesity. However, the roles of individual inflammatory mediators in adipose tissue are poorly understood. Objectives: The objective of this study was to determine which inflammation markers are most overexpressed at the gene level in adipose tissue in human obesity and how this relates to corresponding protein secretion. Design: We examined gene expression profiles in 17 lean and 20 obese subjects. The secretory pattern of relevant corresponding proteins was examined in human sc adipose tissue or isolated fat cells in vitro and in vivo in several obese or lean cohorts. Results: In ranking gene expression, defined pathways associated with obesity and immune and defense responses scored high. Among seven markedly overexpressed chemokines, only monocyte chemoattractant protein 1 (MCP1) was released from adipose tissue and isolated fat cells in vitro. In obesity, the secretion and expression of MCP1 in adipose tissue pieces were more than 6- and 2-fold increased, respectively, but there was no change in circulating MCP1 levels. There was no net release of MCP1, but there was a net release of leptin, in vivo from adipose tissue into the circulation. Conclusions: Obesity is associated with the increased expression of several chemokine genes in adipose tissue. However, only MCP1 is secreted into the extracellular space, where it primarily acts as a local factor, because little or no spillover into the circulation occurs. MCP1 influences the function of adipocytes, is a recruitment factor for macrophages, and may be a crucial link among chemokines between adipose tissue inflammation and insulin resistance.
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29.
  • Davidsson, Pia, 1962, et al. (författare)
  • Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients.
  • 2002
  • Ingår i: Neuroreport. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4965. ; 13:5, s. 611-5
  • Tidskriftsartikel (refereegranskat)abstract
    • By comparing the CSF proteome between Alzheimer disease (AD) patients and controls it may be possible to identify proteins that play a role in the disease process and thus to study the pathogenesis of AD. We used mini-gel technology in a two-dimensional electrophoresis procedure, sensitive SYPRO Ruby staining and mass spectrometry for clinical screening of disease-influenced CSF proteins in 15 AD patients and 12 controls. The levels of six proteins and their isoforms, including proapolipoprotein, apolipoprotein E, beta-2 microglobulin, retinol-binding protein, transthyretin, and ubiquitin, were significantly altered in CSF of AD patients. The most prominently altered proteins were the apolipoproteins, especially proapolipoprotein.
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30.
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31.
  • Dellenmark-Blom, Maria, 1983, et al. (författare)
  • Family screening for neurodevelopmental problems and its associations with child cognitive function enable tailored treatment for childhood obesity
  • 2024
  • Ingår i: ACTA PAEDIATRICA. - 0803-5253 .- 1651-2227.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To identify neurodevelopmental disorders in children with obesity, and investigate associations to cognitive functions as well as parents' self-reported neurodevelopmental problems. Methods: Eighty children were included at two outpatient obesity clinics in Sweden 2018-2019. Of these, 50 children without previously diagnosed neurodevelopmental disorders were screened, and so were their parents. Children who screened positive for neurodevelopmental problems were referred to a specialised psychiatry unit for further diagnosis. Test results of cognitive functioning were compared with the norm and between study groups by neurodevelopmental diagnoses. Results: Of the screened families, 17/50 children were diagnosed by the psychiatric unit with attention deficit-hyperactivity disorder (ADHD) and 15/82 parents screened positive for neurodevelopmental problems. Having a mother who screened positive for neurodevelopmental problems was associated with child ADHD (p < 0.05). The children's full-scale intelligence quotient (92.86 +/- 12.01, p < 0.001) and working memory index (90.62 +/- 12.17, p < 0.001) were lower than the norm. Working memory index was lower in children with ADHD compared to without ADHD: 84.76 +/- 9.58 versus 94.09 +/- 12.29 (p <= 0.01). Executive constraints were associated with verbal deviances. Conclusion: Increased awareness is needed about the overlap between neurodevelopmental problems and obesity in obesity clinics.
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32.
  • Dickson, Elna, et al. (författare)
  • Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease
  • 2023
  • Ingår i: Journal of Huntington's disease. - 1879-6397. ; 12:3, s. 253-266
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.OBJECTIVE: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice.METHODS: We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony. Gonadal (visceral) and inguinal (subcutaneous) WAT depot weights were monitored, as well as adipocyte size distribution. Response to isoprenaline-stimulated glycerol release and insulin-stimulated glucose uptake in adipocytes from gonadal WAT was assessed.RESULTS: In R6/2 mice, WAT depot weights were comparable to wildtype (WT) mice, and the response to insulin and isoprenaline in gonadal adipocytes was unaltered. Leptin-deficient R6/2 mice exhibited distinct changes compared to leptin-deficient WT mice. At 12 weeks, female leptin-deficient R6/2 mice had reduced body weight accompanied by an increased proportion of smaller adipocytes, while in contrast; male mice displayed a shift towards larger adipocyte sizes without a significant body weight reduction at this timepoint.CONCLUSIONS: We here show that there are early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 mice and leptin-deficient R6/2 mice.
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33.
  • Ek, Hans, et al. (författare)
  • Extramatrical mycelial growth, biomass allocation and nitrogen uptake in ectomycorrhizal systems in response to collembolan grazing
  • 1994
  • Ingår i: Applied Soil Ecology. - : Elsevier BV. - 0929-1393. ; 1:2, s. 155-169
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of Collembola grazing activities on the ectomycorrhizal symbiosis were studied in laboratory microcosms. Pinus contorta seedlings in association with Paxillus involutus were grown in a sandy soil and the Collembola Onychiurus armatus was added in different densities. To study effects on nutrient uptake by the extramatrical mycorrhizal mycelium, cups containing 15NH4+ and phytin amended soil were evenly distributed in the microcosms. These cups were covered with a net that allowed the mycelium to penetrate but neither Collembola nor plant roots. Extramatrical hyphal growth was impeded at a high density of O. Armatus. Low densities of O. armatus increased the extramatrical hyphal growth, the colonization rate of side plants and the biomass of P. involutus. However, the amount of P. involutus on/in the plant roots was not affected. Thus, low densities of collembolans induced a shift towards a larger proportion of P. involutus growing extramatrically. The presence of O. armatus in low numbers enhanced the uptake and transfer of 15N by P. involvus to the plants by up to 76%. The Collembola population growth was not higher in mycorrhizal compared with non-mycorrhizal microcosms while nematode population size was reduced in mycorrhizal compared with non-mycorrhizal microcosms.
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34.
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35.
  • Furingsten, Lovisa, 1974-, et al. (författare)
  • Caring for dying children in an acute paediatric ward
  • 2013
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • IntroductionSwedish acute paediatric wards usually focuses on children with urgent and short-time illnesses and the care is not always suited for a dying child. Caring for dying children in this context therefor faces special challenges and needs to be further investigated through research from the health care professionals´ (HCP) perspective. PurposeThe aim was to describe caring as presented in professional caregivers’ experiences of caring for dying children in paediatric ward. MaterialFour HCP in a paediatric ward, which had been caring for at least one dying child during the last five years, participated. MethodsA phenomenological approach was chosen using qualitative in-depth interviews, starting with one opening question, continuing with follow-up questions according to responsive listening. Data were analysed following four steps suggested by Giorgi: reading to capture the global sense, constitution of parts into ‘meaning units’, transformation from implicit meaning to explicit constituents and gaining structure. ResultsThe findings are represented in five constituents. Presence is a prerequisite for caring when a child is dying. Self-knowledge and support from others are suggested to help when the HCP is suffering and struggling with the injustice in dying. The essence of caring for dying children is like a musical attuned composition. The moments are vulnerable and could easily be disrupted and turn into disharmony. ConclusionsThe HCP needs self-knowledge to be true and sensitive in the perceived situation of injustice when caring for dying children and their families. Caring assumes presence; however, caring for dying children is found to mean suffering to HCP and raises the need for support from others.
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36.
  • Furingsten, Lovisa, 1974-, et al. (författare)
  • Ethical challenges when caring for dying children
  • 2015
  • Ingår i: Nursing Ethics. - : SAGE Publications. - 0969-7330 .- 1477-0989. ; 22:2, s. 176-187
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Caring for dying children presents special challenges, according to the children themselves, their relatives and healthcare professionals. Objective: The aim of this study was to describe caring as represented in healthcare workers' experiences of caring for dying children. Method: A phenomenological approach was chosen, in-depth interviews were carried out and data were analysed in four steps focusing on (a) open reading, (b) meaning units, (c) constituents and (d) essence. Ethical considerations: Four nurses in a general acute paediatric care setting in Sweden participated after providing written informed consent. Voluntary participation and confidentiality were ensured, and the study was ethically approved. Findings: The essence of caring for dying children was likened to a musically attuned composition, comprising five constituents: presence, self-knowledge, injustice in dying, own suffering and in need of others. Presence was found to be a prerequisite for caring when a child is dying. Self-knowledge and support from others can be of help when struggling with emotional pain and injustice. Discussion: Caring for dying children has been found to be a delicate task for healthcare workers all over the world, and the ethical dimension is emphasized in international research. In this study, emotional pain and suffering accompanied caring, but an atmosphere in which it is possible to give and get support from colleagues and to have time to grieve and time to focus on the patient's needs may ease the burden, as can having time to process thoughts about life and death, and a possibility to grow in self-knowledge. Conclusion: Caring in ethically demanding situations may be facilitated through presence, atmosphere, self-knowledge and time. The challenge does not demand highly technological solutions; these assets are readily available, no matter where on earth. However, there is a need to further investigate these prerequisites for caring, particularly when a child is dying.
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37.
  • Grahnemo, Louise, et al. (författare)
  • Identification of three bacterial species associated with increased appendicular lean mass : the HUNT study.
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
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38.
  • Guerra, Lina, et al. (författare)
  • Bacterial genotoxin triggers FEN1-dependent RhoA activation, cytoskeleton remodeling and cell survival
  • 2011
  • Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 124:16, s. 2735-2742
  • Tidskriftsartikel (refereegranskat)abstract
    • The DNA damage response triggered by bacterial cytolethal distending toxins (CDTs) is associated with activation of the actin-regulating protein RhoA and phosphorylation of the downstream-regulated mitogen-activated protein kinase (MAPK) p38, which promotes the survival of intoxicated (i.e. cells exposed to a bacterial toxin) cells. To identify the effectors of this CDT-induced survival response, we screened a library of 4492 Saccharomyces cerevisiae mutants that carry deletions in nonessential genes for reduced growth following inducible expression of CdtB. We identified 78 genes whose deletion confers hypersensitivity to toxin. Bioinformatics analysis revealed that DNA repair and endocytosis were the two most overrepresented signaling pathways. Among the human orthologs present in our data set, FEN1 and TSG101 regulate DNA repair and endocytosis, respectively, and also share common interacting partners with RhoA. We further demonstrate that FEN1, but not TSG101, regulates cell survival, MAPK p38 phosphorylation, RhoA activation and actin cytoskeleton reorganization in response to DNA damage. Our data reveal a previously unrecognized crosstalk between DNA damage and cytoskeleton dynamics in the regulation of cell survival, and might provide new insights on the role of chronic bacteria infection in carcinogenesis.
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39.
  • Guné, Henrik, et al. (författare)
  • Impact of ABO blood group on bleeding complications after surgery for acute type A aortic dissection
  • 2021
  • Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 32:4, s. 253-258
  • Tidskriftsartikel (refereegranskat)abstract
    • Excessive bleeding is a serious complication associated with impaired survival after surgery for acute type A aortic dissection (ATAAD). Different ABO blood groups are associated with variable levels of circulating von Willebrand factor and therefore potentially altered risks of surgical haemorrhage. The current study aimed to assess the impact of blood group on bleeding complications after ATAAD surgery. This was a retrospective cohort study including 336 patients surgically treated for ATAAD between January 2004 and January 2019. Patients with blood group O were compared with non-O patients. In total, 152 blood group O patients were compared with 184 non-O patients. There were no differences in rates of massive bleeding (27.0 vs. 25.5%, P = 0.767) or re-exploration for bleeding (16.4 vs. 13.0%, P = 0.379) in blood group O and non-O patients, respectively. Median chest tube output 12 h after surgery was 520 ml (350-815 ml) in blood group O and 490 ml (278-703 ml) in non-O patients (P = 0.229). Blood group O patients received more fibrinogen concentrate (6.1 ± 4.0 vs. 4.9 ± 3.3 g, P = 0.023) but administered units of packed red blood cells [5 (2-8) vs. 4 (2-9) U, P = 0.736], platelets [4 (2-4) vs. 3 (2-5) U, P = 0.521] or plasma [4 (1-7) vs. 4 (0-7) U, P = 0.562] were similar. This study could not demonstrate any association between blood group and bleeding after surgery for ATAAD. It cannot be ruled out that potential differences were levelled out by blood group O patients receiving significantly more fibrinogen concentrate.
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40.
  • Gustafsson, Maria-Therese, 1979- (författare)
  • Beyond Conflict and Conciliation : The Implications of different forms of Corporate-Community Relations in the Peruvian Mining Industry
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In Peru, the rapid expansion of extractive activities has led to increased mobilization by peasant communities. In remote rural areas, the mediating efforts of the state between communities and corporations are often weak, and corporations have played an important role in dealing with communities’ demands and protests through different strategies. These processes are illustrative of a broader trend in which private corporations engage in governance processes by assuming state-like functions in relation to citizens. This study investigates how communities’ mobilization and scope of influence is affected by their interactions with corporations. Based on interviews and written primary sources, the study provides a detailed empirical account of the multifaceted relations and negotiations between corporations and communities in the context of two macro-economically significant Peruvian mining projects – Rio Blanco and Las Bambas. In this way, the study contributes to the empirical and theoretical debates on the political role of corporations and the implications for social movements and democratic influence.The study shows that the presence of private corporations alters the conditions for mobilization by creating opportunities as well as constraints, with significant impact on mobilization structures and framing of demands. However, communities relate to those opportunities and constraints differently, depending on how state-society relations and other forms of private dynamics have played out historically at the subnational level.
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41.
  • Hedlund, Katarina, et al. (författare)
  • Tritrophic interactions in a soil community enhance decomposition rates
  • 2000
  • Ingår i: Oikos. - : Wiley. - 1600-0706 .- 0030-1299. ; 88:3, s. 585-591
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbivorous soil fauna can influence decomposition rates by regulating biomass and composition of the microbial community. The idea that predators at higher trophic levels regulate population densities of microbivorous fauna and thus indirectly increase microbial growth and activity has often been suggested but rarely examined in soil ecosystems. In this paper the effects of tritrophic interactions on decomposition processes in the soil are studied and expressed as soil respiration, hyphal lengths, cellulase and chitinase activities. The experiments were carried out in soil microcosms in a factorial design with three fungal species (Alternaria alternata, Fusarium oxysporum, Trichoderma viride), the fungivorous collembolan Folsomia fimetaria and the predatory mite Hypoaspis aculeifer. The respiration rate was significantly higher with three trophic levels than in those with two and lowest in those with only fungi present. This indicates that a low level of grazing stimulates microbial respiration more than a high level or no grazing at ail. The effect was similar for all three fungal species but most pronounced in microcosms with the fungus A. alternata which was a preferred food source by the collembolans. Hyphal lengths were in all cases but with T, viride reduced in the presence of collembolans and predatory mites. T. viride had a slightly higher chitinase activity than the other fungi but increased numbers of trophic levels did not affect the enzymatic activities of any of the fungi.
  •  
42.
  • Hien, Tran T., et al. (författare)
  • MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle
  • 2018
  • Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 233:9, s. 7195-7205
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes is a major risk factor for cardiovascular disease and this is in part due to the effects of hyperglycemia on vascular smooth muscle cells. Small non-coding microRNAs are known to control smooth muscle phenotype and arterial contractility and are dysregulated in diabetes. The effect of microRNAs on smooth muscle differentiation is in part mediated by the transcription factor KLF4 but the role of this mechanism in diabetic vascular disease is not fully understood. Herein, we have investigated the importance of hyperglycemia and diabetes for the expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle cells and similar results were found in arteries of diabetic mice and patients. This correlated with a Foxa2-dependent up-regulation of miR-29c, which targeted KLF4 in vascular smooth muscle cells. Importantly, by preventing downregulation of KLF4, the induction of smooth muscle contractile protein markers by glucose was inhibited. In conclusion, miR-29 mediated inhibition of KLF4 in hyperglycemic conditions contributes to increased expression of contractile markers in vascular smooth muscle cells. Further studies are warranted to determine the therapeutic implications of miR-29 inhibition in diabetic vascular disease.
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43.
  • Hien Tran, Thi, et al. (författare)
  • Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization.
  • 2016
  • Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 291:7, s. 68-3552
  • Tidskriftsartikel (refereegranskat)abstract
    • Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hyper-contractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, qPCR and western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers was increased in isolated smooth muscle cells cultured under high compared to low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization and myocardin related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.
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44.
  • Himmerich, Hubertus, et al. (författare)
  • World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders
  • 2023
  • Ingår i: World Journal of Biological Psychiatry. - : Taylor & Francis. - 1562-2975 .- 1814-1412. ; 24:8, s. 643-706
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: This 2023 update of the WFSBP guidelines for the pharmacological treatment of eating disorders (EDs) reflects the latest diagnostic and psychopharmacological progress and the improved WFSBP recommendations for the assessment of the level of evidence (LoE) and the grade of recommendation (GoR).Methods: The WFSBP Task Force EDs reviewed the relevant literature and provided a timely grading of the LoE and the GoR.Results: In anorexia nervosa (AN), only a limited recommendation (LoE: A; GoR: 2) for olanzapine can be given, because the available evidence is restricted to weight gain, and its effect on psychopathology is less clear. In bulimia nervosa (BN), the current literature prompts a recommendation for fluoxetine (LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1). In binge-eating disorder (BED), lisdexamfetamine (LDX; LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1) can be recommended. There is only sparse evidence for the drug treatment of avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD).Conclusion: In BN, fluoxetine, and topiramate, and in BED, LDX and topiramate can be recommended. Despite the published evidence, olanzapine and topiramate have not received marketing authorisation for use in EDs from any medicine regulatory agency.
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45.
  • Hoban, Sean, et al. (författare)
  • Monitoring status and trends in genetic diversity for the Convention on Biological Diversity : An ongoing assessment of genetic indicators in nine countries
  • 2023
  • Ingår i: Conservation Letters. - 1755-263X. ; 16:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent scientific evidence shows that genetic diversity must be maintained, managed, and monitored to protect biodiversity and nature's contributions to people. Three genetic diversity indicators, two of which do not require DNA-based assessment, have been proposed for reporting to the Convention on Biological Diversity and other conservation and policy initiatives. These indicators allow an approximation of the status and trends of genetic diversity to inform policy, using existing demographic and geographic information. Application of these indicators has been initiated and here we describe ongoing efforts in calculating these indicators with examples. We specifically describe a project underway to apply these indicators in nine countries, provide example calculations, address concerns of policy makers and implementation challenges, and describe a roadmap for further development and deployment, incorporating feedback from the broader community. We also present guidance documents and data collection tools for calculating indicators. We demonstrate that Parties can successfully and cost-effectively report these genetic diversity indicators with existing biodiversity observation data, and, in doing so, better conserve the Earth's biodiversity. 
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46.
  • Hoque, Sanzana, et al. (författare)
  • Skeletal muscle regeneration is altered in the R6/2 mouse model of Huntington’s disease
  • 2022
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Huntington’s disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise.In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice.We found that, similar to R6/2 adult mice, neonatal R6/2 mice also exhibit a significant reduction in myofiber width and morphological changes in gastrocnemius and soleus muscles compared to WT mice. Cardiotoxin (CTX)-induced acute muscle damage in R6/2 and WT mice showed that the Pax7+ satellite cell pool was dampened in R6/2 mice at 4 weeks post-injection, and R6/2 mice exhibited an altered inflammatory profile in response to acute damage.Our results suggest that, in addition to the mutant HTT degenerative effects in mature muscle fibers, expression of mutant HTT in satellite cells might alter developmental and regenerative processes to contribute to the progressive muscle mass loss in HD. Taken together, the results presented here encourage further studies evaluating the underlying mechanisms of satellite cell dysfunction in HD mouse models.
  •  
47.
  • Hult, Erica, 1976- (författare)
  • The Proliferation of Evidence-based Medicine : Ideas, Translations and Advocates
  • 2012
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In the last few decades, the idea of evidence-based medicine (EBM) has proliferated throughout the world. EBM is, in its essence, an idea that is based on the assumption that doctors need to integrate evidence from clinical research into their patient care. This study contributes to Scandinavian institutionalism by exploring how EBM has proliferated in processes of translation and why EBM has proliferated in this way. The study is based on documents, interviews and participant observations. It investigates the translations of EBM in biomedical journals 1992-2002, guiding us in particular through discussions on EBM in three general medical journals that transformed the content and shape of the idea but also contributed to the circulation of it. Also, the study examines three advocates of EBM; Evidence-Based Medicine Working Group, the Cochrane Collaboration and Swedish Council on Technology Assessment in Healthcare (SBU). In this way, it highlights dynamics in idea proliferation.The study shows how EBM was translated into a broad and ambiguous idea as it travelled across time and space. EBM developed from criticisms advanced by medical educators at a Canadian university hospital to an idea for medical practice developed by doctors as well as by those in the medical environment. The translations of EBM into a broad and ambiguous idea meant that the idea moved beyond the pressure to examine evidence from clinical research – it combined the examination of evidence from clinical research with clinical expertise and patient views. The study demonstrates that the translation processes involved interplay and contestations among the individuals and organisations engaged in EBM.These results suggest that EBM proliferated in translation processes that were created and set in motion through contestations that incorporated the limitations found in EBM. Much of what seemed, at first sight, to be limitations to and criticisms levelled against EBM should thus ultimately be reinterpreted as many steps pushing for the translations of the idea. The advocates studied translated EBM in accordance with their own interests and work, in this way developing important although disparate roles. It appears from the results of the study that EBM was translated differently depending on the context in which the translation took place (the context of the translation) and the context of the advocates. EBM was translated into a broad and ambiguous idea by being mixed with various traditions and fields of knowledge and other ideas and models, and developed for existing local practices in organisations and work fields.
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48.
  •  
49.
  • Jansson, John-Olov, 1954, et al. (författare)
  • Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
  • 2018
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
  • Tidskriftsartikel (refereegranskat)abstract
    • Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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50.
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