| 1. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
| 2. |
- Eriksson K., Susanna, et al.
(författare)
-
Geometrical and energetical structural changes in organic dyes for dye-sensitized solar cells probed using photoelectron spectroscopy and DFT
- 2016
-
Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:1, s. 252-260
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of alkoxy chain length in triarylamine based donor acceptor organic dyes are investigated with respect to the electronic and molecular surface structures on the performance of solar cells and the electron lifetime. The dyes were investigated when adsorbed on TiO2 in a configuration that can be used for dye sensitized solar cells (DSCs). Specifically, the two dyes D35 and D45 were compared using photoelectron spectroscopy (PES) and density functional theory (DFT) calculations. The differences in solar cell characteristics when longer alkoxy chains are introduced in the dye donor unit are attributed to geometrical changes in dye packing while only minor differences were observed in the electronic structure. A higher dye load was observed for D45 on TiO2. However, D35 based solar cells result in higher photocurrent although the dye load is lower. This is explained by different geometrical structures of the dyes on the surface.
|
|
| 3. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 4. |
- Ried, Janina S., et al.
(författare)
-
A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
|
|
| 5. |
- Shungin, Dmitry, et al.
(författare)
-
New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
|
|
| 6. |
- Speliotes, Elizabeth K., et al.
(författare)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Aasa, Anna, et al.
(författare)
-
Collecting dialect data and making use of them an interim report from Swedia 2000
- 2000
-
Ingår i: Proceedings FONETIK 2000. ; , s. 17-20
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper consists of two, somewhat disparate parts. In the first part, some experiences of two years of fieldwork are summarized, concentrating, as the subtitle suggests, on the very heart of phonetic fieldwork: the encounters and interviews with the informants. As a result of the fieldwork, the project now has access to recordings from approximately 1300 speakers of more than 100 dialects of Swedish. We are currently initiating research on various aspects of the sound patterns of these dialects. The second part of the paper is meant to give an overview of some of our research plans for the near future.
|
|
| 10. |
- Aasa, Anna, et al.
(författare)
-
Vowel quantity in West Swedish - the villain of the piece?
- 2000
-
Ingår i: Proceedings of the Swedish Phonetics Conference FONETIK 2000.. ; , s. 17-20
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper consists of two, somewhat disparate parts. In the first part, some experiences of two years of fieldwork are summarized, concentrating, as the subtitle suggests, on the very heart of phonetic fieldwork: the encounters and interviews with the informants. As a result of the fieldwork, the project now has access to recordings from approximately 1300 speakers of more than 100 dialects of Swedish. We are currently initiating research on various aspects of the sound patterns of these dialects. The second part of the paper is meant to give an overview of some of our research plans for the near future.
|
|
| 11. |
|
|
| 12. |
- Ahlinder, Jon, et al.
(författare)
-
Upstream land use with microbial downstream consequences : iron and humic substances link to Legionella spp
- 2024
-
Ingår i: Water Research. - : Elsevier. - 0043-1354 .- 1879-2448. ; 256
-
Tidskriftsartikel (refereegranskat)abstract
- Intensified land use can disturb water quality, potentially increasing the abundance of bacterial pathogens, threatening public access to clean water. This threat involves both direct contamination of faecal bacteria as well as indirect factors, such as disturbed water chemistry and microbiota, which can lead to contamination. While direct contamination has been well described, the impact of indirect factors is less explored, despite the potential of severe downstream consequences on water supply. To assess direct and indirect downstream effects of buildings, farms, pastures and fields on potential water sources, we studied five Swedish lakes and their inflows. We analysed a total of 160 samples in a gradient of anthropogenic activity spanning four time points, including faecal and water-quality indicators. Through species distribution modelling, Random Forest and network analysis using 16S rRNA amplicon sequencing data, our findings highlight that land use indirectly impacts lakes via inflows. Land use impacted approximately one third of inflow microbiota taxa, in turn impacting ∌20–50 % of lake taxa. Indirect effects via inflows were also suggested by causal links between e.g. water colour and lake bacterial taxa, where this influenced the abundance of several freshwater bacteria, such as Polynucleobacter and Limnohabitans. However, it was not possible to identify direct effects on the lakes based on analysis of physiochemical- or microbial parameters. To avoid potential downstream consequences on water supply, it is thus important to consider possible indirect effects from upstream land use and inflows, even when no direct effects can be observed on lakes. Legionella (a genus containing bacterial pathogens) illustrated potential consequences, since the genus was particularly abundant in inflows and was shown to increase by the presence of pastures, fields, and farms. The approach presented here could be used to assess the suitability of lakes as alternative raw water sources or help to mitigate contaminations in important water catchments. Continued broad investigations of stressors on the microbial network can identify indirect effects, avoid enrichment of pathogens, and help secure water accessibility.
|
|
| 13. |
- Anastasopoulou, Stavroula, et al.
(författare)
-
Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes
- 2020
-
Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 107:10, s. 2318-2328
-
Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged >= 10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P < 0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10(-6)), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients < 10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.
|
|
| 14. |
- Anastasopoulou, Stavroula, et al.
(författare)
-
Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia : Clinical characteristics, risk factors, course, and outcome of disease
- 2019
-
Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 66:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).Procedure: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.Results: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.Conclusion: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.
|
|
| 15. |
- Anastasopoulou, Stavroula, et al.
(författare)
-
Seizures during treatment of childhood acute lymphoblastic leukemia : A population-based cohort study
- 2020
-
Ingår i: European journal of paediatric neurology. - : ELSEVIER SCI LTD. - 1090-3798 .- 1532-2130. ; 27, s. 72-77
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Seizures are common in children with acute lymphoblastic leukemia (ALL). As ALL survival rates are improving, the challenge to minimize treatment related side effects and late sequelae rises. Here, we studied the frequency, timing, etiology and risk factors of seizures in ALL patients. Methods: The study included children aged 1-17.9 years at diagnosis of B-cell-precursor and T cell ALL who were treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2015. Detailed patient data were acquired from the NOPHO ALL2008 registry and by review of medical records. Results: Seizures occurred in 81/1464 (5.5%) patients. The cumulative incidence of seizures at one months was 1.7% (95% CI: 1.2-2.5) and at one year 5.3% (95% CI 4.2-6.5%). Patients aged 10-17.9 years, those with T cell immunophenotype, CNS involvement, or high-risk induction with dexamethasone had higher risk for seizures in univariable analyses. Only age remained a risk factor in multivariable analyses (the cumulative incidence of seizures for patients 10-17.9 years old at one year was 9.0% (95% CI: 6.2-12.9)). Of the 81 patients with seizures, 43 had posterior reversible encephalopathy syndrome (PRES), 15 had isolated seizures, nine had sinus venous thrombosis (SVT), three had stroke-like syndrome, and 11 had other neurotoxicities. Epilepsy diagnosis was reported in totally 11 ALL survivors at last follow up. Conclusion: Seizures are relatively common in ALL patients and occur most often in patients with PRES, SVT, or as an isolated symptom. Older children have higher risk of seizures. (C) 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
|
|
| 16. |
- Appelqvist, Hanna, et al.
(författare)
-
Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes
- 2013
-
Ingår i: Journal of Cell Science. - : Company of Biologists. - 0021-9533 .- 1477-9137. ; 126:24, s. 5578-5584
-
Tidskriftsartikel (refereegranskat)abstract
- Ultraviolet (UV) irradiation is a major environmental carcinogen involved in the development of skin cancer. To elucidate the initial signaling during UV-induced damage in human keratinocytes, we investigated lysosomal exocytosis and apoptosis induction. UVA, but not UVB, induced plasma membrane damage, which was repaired by Ca2+-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in extracellular release of cathepsin D and acid sphingomyelinase (aSMase). Two hours after UVA irradiation, we detected activation of caspase-8, which was reduced by addition of anti-aSMAse. Furthermore, caspase-8 activation and apoptosis was reduced by prevention of endocytosis and by the use of cathepsin inhibitors. We conclude that lysosomal exocytosis is part of the keratinocyte response to UVA and is followed by cathepsin-dependent activation of caspase-8. The findings have implications for the understanding of UV-induced skin damage and emphasize that UVA and UVB initiate apoptosis through different signaling pathways in keratinocytes.
|
|
| 17. |
- Assarlind, Marcus, 1983, et al.
(författare)
-
Adopting new ways of working in small and medium-sized enterprises: findings from interventions in 12 European companies
- 2013
-
Ingår i: Total Quality Management and Business Excellence. - : Informa UK Limited. - 1478-3371 .- 1478-3363. ; 24:8, s. 945-958
-
Tidskriftsartikel (refereegranskat)abstract
- This paper elaborates on the factors to be considered in order for interventions (activities aimed at introducing new ways of working through a series of focused activities in an organisation) to lead to long-term effects inside small and medium-sized enterprises (SMEs). Its purpose of it is to describe how interventions can be carried out in order for SMEs to adopt new ways of working by understanding the context, process and content of an intervention. The results of this study suggest that in designing interventions for the SMEs, the context aspects of an intervention must be carefully considered. Not only is the process or context of an intervention important, but so is the content. As a consequence, we suggest content that accomplishes the following: (1) supports the formulation of strategies; (2) encourages dialogue and (3) uses company data. The paper is based on a multiple case study of 12 SMEs from 6 European countries undergoing similar interventions within the FutureSME project. These long-term relationships within a large-scale project have provided access and a rare opportunity to conduct research on this often overlooked business sector. The empirical data have been collected through company presentations, structured reports and narratives. The material has been subject to a cross-case analysis.
|
|
| 18. |
- Assarlind, Marcus, 1983, et al.
(författare)
-
Designing interventions in SMEs: Experiences from a pan-European multiple case study
- 2012
-
Ingår i: Proceedings of the 15th QMOD-ICQSS conference. - 9788389333469 ; , s. 123-135
-
Konferensbidrag (refereegranskat)abstract
- PurposeThe purpose of this paper is to describe how interventions can be carried out in order for small and medium sized companies (SMEs) to adopt new ways of working, by understanding the context, process and content of the intervention. Interventions are defined as activities aimed at introducing new ways of working through a series of focused activities in the organization.Design/methodology/approachThe work was part of an EU-funded project called FutureSME aiming at aiding SMEs in becoming more competitive. This paper is based on a multiple case study of twelve SMEs from six European countries undergoing similar interventions. The empirical data has been collected through presentations by company representatives, A3 reports including structured information about the intervention and its outcome, and case essays containing subjective descriptions of respective company’s experiences from the interventions. The material has been subject to a cross-case analysis.FindingsThis paper elaborates on previous research on important factors to consider in order for interventions to lead to long-term effects in SMEs. The results from this study suggest that in the design of the interventions at SMEs, one needs to carefully consider the context aspects regarding the intervention, which is seen as a deficiency in the project. It is also pointed out that not only the process or context of the intervention is of importance, but also the content. We suggest content that 1) supports the formulation of strategies, 2) encourages dialogue, and 3) uses company data. Hence, when designing an intervention in SMEs it is beneficial if the content have such characteristics, and by inclusion both short-term success and long-term sustainability are more likely as a result of the intervention.Research limitations/implicationsThis paper does not deal with how to motivate SMEs to initiate an intervention process.Originality/valueIntervention studies have mostly focused on larger companies. The special set-up with dedicated external support and a long term relationship within a large-scale project has provided access to a study of twelve SMEs across Europe and has provided a rare opportunity for research.
|
|
| 19. |
- Baumgarten, Thomas, et al.
(författare)
-
Isolation and characterization of the E. coli membrane protein production strain Mutant56(DE3)
- 2017
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Membrane protein production is usually toxic to E. coli. However, using genetic screens strains can be isolated in which the toxicity of membrane protein production is reduced, thereby improving production yields. Best known examples are the C41(DE3) and C43(DE3) strains, which are both derived from the T7 RNA polymerase (P)-based BL21(DE3) protein production strain. In C41(DE3) and C43(DE3) mutations lowering t7rnap expression levels result in strongly reduced T7 RNAP accumulation levels. As a consequence membrane protein production stress is alleviated in the C41(DE3) and C43(DE3) strains, thereby increasing membrane protein yields. Here, we isolated Mutant56(DE3) from BL21(DE3) using a genetic screen designed to isolate BL21(DE3)-derived strains with mutations alleviating membrane protein production stress other than the ones in C41(DE3) and C43(DE3). The defining mutation of Mutant56(DE3) changes one amino acid in its T7 RNAP, which weakens the binding of the T7 RNAP to the T7 promoter governing target gene expression rather than lowering T7 RNAP levels. For most membrane proteins tested yields in Mutant56(DE3) were considerably higher than in C41(DE3) and C43(DE3). Thus, the isolation of Mutant56(DE3) shows that the evolution of BL21(DE3) can be promoted towards further enhanced membrane protein production.
|
|
| 20. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
|
|
| 21. |
- Blomgran, Robert, et al.
(författare)
-
Common Genetic Variations in the NALP3 Inflammasome Are Associated with Delayed Apoptosis of Human Neutrophils
- 2012
-
Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Neutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1 beta production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages. less thanbrgreater than less thanbrgreater thanMethods and Findings: Patients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response. less thanbrgreater than less thanbrgreater thanConclusions: The Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.
|
|
| 22. |
- Brukas, Vilis, et al.
(författare)
-
How Sensitive Are Ecosystem Services in European Forest Landscapes to Silvicultural Treatment?
- 2015
-
Ingår i: Forests. - : MDPI AG. - 1999-4907. ; 6, s. 1666-1695
-
Tidskriftsartikel (refereegranskat)abstract
- While sustainable forestry in Europe is characterized by the provision of a multitude of forest ecosystem services, there exists no comprehensive study that scrutinizes their sensitivity to forest management on a pan-European scale, so far. We compile scenario runs from regionally tailored forest growth models and Decision Support Systems (DSS) from 20 case studies throughout Europe and analyze whether the ecosystem service provision depends on management intensity and other co-variables, comprising regional affiliation, social environment, and tree species composition. The simulation runs provide information about the case-specifically most important ecosystem services in terms of appropriate indicators. We found a strong positive correlation between management intensity and wood production, but only weak correlation with protective and socioeconomic forest functions. Interestingly, depending on the forest region, we found that biodiversity can react in both ways, positively and negatively, to increased management intensity. Thus, it may be in tradeoff or in synergy with wood production and forest resource maintenance. The covariables species composition and social environment are of punctual interest only, while the affiliation to a certain region often makes an important difference in terms of an ecosystem service's treatment sensitivity.
|
|
| 23. |
|
|
| 24. |
- Carlander, Ida, et al.
(författare)
-
The Distrained Masculinity
- 2016
-
Ingår i: EPAC 2015. - Newmarket : Hayward Medical Communications. - 9780954202231 ; , s. 206-
-
Konferensbidrag (refereegranskat)abstract
- Dying is a gendered situated experience. Relatively few discussions about death and dying have looked beyond patient perspective in relation to culture and images of men and masculinity. Despite a growing body of literature on dying, criticalstudies about men and masculinitiesin relation to thisis needed. Aim: The aim wasto describe the perceived and self-reflected processes of dying in relation to gendered ideas of culture, family and identity. Methods: We used a narrative thematic approach to analyse 8 interviews conducted over 18 month with one man close to death. The analysisfocuses on the interplay of death and dying and examines how they can be related to the concept of hegemonic masculinity and the processes connecting such men with the position of being. Result: Three themes are presented here: The priorities – straightened, the body – revised, the fatherhood – comprised. Setting the prioritiesstraight when time was meted out entails revising norms connected to work and what it meansto be a“real”man. The navigation towards child-centered manhood representsinstant re-evaluation of work. The presence of body is a deeply rooted foundation in perceptions and ideas of masculinity. Hence, the body is often regarded as a machine, i.e. working and operating in socialsituations, and bodily decline is a dispossession of masculinity. Achieving the goal of a“positively involved fatherhood”indicatesthat the amount of involvement mattersin contemporary masculinity. Being presentseemsto involve a range of responsibilities,such as economy, practical and emotionalstrings even beyond death. Conclusion: The overarching“distrained masculinity”usesimages and ideals astoolsto reach last possible opportunitiesfor fulfillment rather than filling a function as a style and posing in gendered meanings, covering strategies of: concentration asin putting priorities wright, dispossession or loss due to bodily decline and, extension of responsibilities beyond death.
|
|
| 25. |
|
|
| 26. |
- Dastani, Zari, et al.
(författare)
-
Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
|
|
| 27. |
- Davies, G., et al.
(författare)
-
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
|
|
| 28. |
- Egeblad, Louise, et al.
(författare)
-
Structural and functional studies of the human phosphoribosyltransferase domain containing protein 1
- 2010
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:23, s. 4920-30
-
Tidskriftsartikel (refereegranskat)abstract
- Human hypoxanthine-guanine phosphoribosyltransferase (HPRT) (EC 2.4.2.8) catalyzes the conversion of hypoxanthine and guanine to their respective nucleoside monophosphates. Human HPRT deficiency as a result of genetic mutations is linked to both Lesch-Nyhan disease and gout. In the present study, we have characterized phosphoribosyltransferase domain containing protein 1 (PRTFDC1), a human HPRT homolog of unknown function. The PRTFDC1 structure has been determined at 1.7 Å resolution with bound GMP. The overall structure and GMP binding mode are very similar to that observed for HPRT. Using a thermal-melt assay, a nucleotide metabolome library was screened against PRTFDC1 and revealed that hypoxanthine and guanine specifically interacted with the enzyme. It was subsequently confirmed that PRTFDC1 could convert these two bases into their corresponding nucleoside monophosphate. However, the catalytic efficiency (k(cat)/K(m)) of PRTFDC1 towards hypoxanthine and guanine was only 0.26% and 0.09%, respectively, of that of HPRT. This low activity could be explained by the fact that PRTFDC1 has a Gly in the position of the proposed catalytic Asp of HPRT. In PRTFDC1, a water molecule at the position of the aspartic acid side chain position in HPRT might be responsible for the low activity observed by acting as a weak base. The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway.
|
|
| 29. |
- Eriksson, Anders, et al.
(författare)
-
Implication of coronin 7 in body weight regulation in humans, mice and flies
- 2015
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a growing global concern with strong associations with cardiovascular disease, cancer and type-2 diabetes. Although various genome-wide association studies have identified more than 40 genes associated with obesity, these genes cannot fully explain the heritability of obesity, suggesting there may be other contributing factors, including epigenetic effects. Results: We performed genome wide DNA methylation profiling comparing normal-weight and obese 9-13 year old children to investigate possible epigenetic changes correlated with obesity. Of note, obese children had significantly lower methylation levels at a CpG site located near coronin 7 (CORO7), which encodes a tryptophan-aspartic acid dipeptide (WD)-repeat containing protein most likely involved in Golgi complex morphology and function. Anatomical profiling of coronin 7 (Coro7) mRNA expression in mice revealed that it is highly expressed in appetite and energy balance regulating regions, including the hypothalamus, striatum and locus coeruleus, the main noradrenergic brain site. Interestingly, we found that food deprivation in mice downregulates hypothalamic Coro7 mRNA levels, and injecting ethanol, an appetite stimulant, increased the number of Coro7 expressing cells in the locus coeruleus. Finally, by employing the genetically-tractable Drosophila melanogaster model we were able to demonstrate an evolutionarily conserved metabolic function for the CORO7 homologue pod1. Knocking down the pod1 in the Drosophila adult nervous system increased their resistance to starvation. Furthermore, feeding flies a high-calorie diet significantly increased pod1 expression. Conclusion: We conclude that coronin 7 is involved in the regulation of energy homeostasis and this role stems, to some degree, from the effect on feeding for calories and reward.
|
|
| 30. |
- Eriksson, Carl, 1981-, et al.
(författare)
-
Changes in medical management and colectomy rates : a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010
- 2017
-
Ingår i: Alimentary Pharmacology and Therapeutics. - Hoboken, USA : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 46:8, s. 748-757
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown.Aim: To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010.Methods: Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Orebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005.Results: The annual age-standardised incidence increased from 3.5 to 18.5 per 100 000 during the study period (P < .01). Correspondingly, the prevalence increased from 44 to 474 per 100 000 between 1965 and 2010. A higher proportion of males than females had extensive colitis at diagnosis (odds ratio: 1.55; 95% CI 1.17-2.05; P < .01). The risk for progression in disease extent was 34.5% and 18.5% at 10 years, for patients with proctitis and left-sided colitis, respectively (P < .01). The use of 5-aminosalicylates, within 10 years, rise from 79% to 92% between 1963-1975 and 1976-1990 (P < .01). Thiopurine use increased from 7% in 1976-1990 to 34% during 1991-2005 (P < .01). The colectomy rate at 10 years was 13.5% (95% CI 11.1%-15.8%), and the risk was lower among patients diagnosed in 1991-2005 compared to 1963-1975 (adjusted hazard ratio: 0.61; 95% CI 0.39-0.94; P = .02).Conclusion: The incidence and prevalence of UC increased over time, and the observed prevalence in 2010 is among the highest reported. In parallel, a decrease in colectomy rates was observed during the most recent decades, potentially reflecting improved medical treatment.
|
|
| 31. |
|
|
| 32. |
- Eriksson, Camilla, et al.
(författare)
-
Epitopes displayed in a cyclic peptide scaffold bind SARS-CoV-2 antibodies
- 2023
-
Ingår i: ChemBioChem. - : Wiley-VCH Verlagsgesellschaft. - 1439-4227 .- 1439-7633. ; 24:15
-
Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus that causes COVID-19 is a global health issue. The spread of the virus has resulted in seven million deaths to date. The emergence of new viral strains highlights the importance of continuous surveillance of the SARS-CoV-2 virus by using timely and accurate diagnostic tools. Here, we used a stable cyclic peptide scaffolds to present antigenic sequences derived from the spike protein that are reactive to SARS-CoV-2 antibodies. Using peptide sequences from different domains of SARS-CoV-2 spike proteins, we grafted epitopes on the peptide scaffold sunflower trypsin inhibitor 1 (SFTI-1). These scaffold peptides were then used to develop an ELISA to detect SARS-CoV-2 antibodies in serum. We show that displaying epitopes on the scaffold improves reactivity overall. One of the scaffold peptides (S2_1146-1161_c) has reactivity equal to that of commercial assays, and shows diagnostic potential.
|
|
| 33. |
|
|
| 34. |
- Eriksson, Carl, 1981-, et al.
(författare)
-
Incidence, prevalence and clinical outcome of anaemia in inflammatory bowel disease : a population-based cohort study
- 2018
-
Ingår i: Alimentary Pharmacology and Therapeutics. - : Blackwell Science Ltd.. - 0269-2813 .- 1365-2036. ; 48:6, s. 638-645
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The incidence and short-term outcome of anaemia in inflammatory bowel disease (IBD) are largely unknown.AIM: To determine the incidence, prevalence and clinical outcome of anaemia in terms of resolution of anaemia within 12 months. We also planned to assess risk factors for anaemia in IBD.METHODS: A random sample of 342 patients was obtained from the population-based IBD cohort of Örebro University Hospital, Sweden, consisting of 1405 patients diagnosed between 1963 and 2010. Haemoglobin measurements recorded from 1 January 2011 to 31 December 2013 were extracted from the Clinical Chemistry data system.RESULTS: In Crohn's disease, the incidence rate of anaemia was 19.3 (95% CI: 15.4-23.7) per 100 person-years and the prevalence was 28.7% (CI: 22.0-36.2), compared with 12.9 (CI: 9.8-16.5) and 16.5% (CI: 11.2-22.9) for ulcerative colitis. Crohn's disease was associated with an increased incidence (OR = 1.60; CI: 1.02-2.51) and prevalence of anaemia (OR = 2.04; CI: 1.20-3.46) compared to ulcerative colitis. Stricturing disease phenotype in Crohn's disease (HR = 2.59; CI: 1.00-6.79) and extensive disease in ulcerative colitis (HR = 2.40; CI: 1.10-5.36) were associated with an increased risk of anaemia. Despite a higher probability of receiving specific therapy within 3 months from the diagnosis of anaemia, Crohn's disease patients had a worse outcome in terms of resolution of anaemia within 12 months (56% vs 75%; P = 0.03).CONCLUSIONS: Anaemia is a common manifestation of IBD even beyond the first years after the diagnosis of IBD. Crohn's disease is associated with both an increased risk and a worse outcome.
|
|
| 35. |
- Eriksson Crommert, Martin, 1974-, et al.
(författare)
-
Predictors of disability attributed to symptoms of increased interrecti distance in women after childbirth : an observational study
- 2021
-
Ingår i: Physical Therapy. - : Oxford University Press. - 0031-9023 .- 1538-6724. ; 101:6
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to investigate how various physical and psychological factors are linked to disability attributed to symptoms from increased interrecti distance (IRD) in women after childbirth.METHODS: In this cross-sectional observational study, 141 women with an IRD of at least 2 finger widths and whose youngest child was between the ages of 1 and 8 years participated. A multilinear regression model was performed with disability as the outcome variable and fear-avoidance beliefs, emotional distress, body mass index, lumbopelvic pain, IRD, and physical activity level as predictor variables.RESULTS: The regression model accounted for 60% (R2 = 0.604, adjusted R2 = 0.586) of the variance in disability (F6,132 = 33.5). The 2 strongest predictors were lumbopelvic pain with a regression coefficient of 1.4 (95% CI = 1.017 to 1.877) and fear avoidance with a regression coefficient of 0.421 (95% CI = 0.287 to 0.555). The actual IRD, with a regression coefficient of -0.133 (95% CI = -1.154 to 0.888), did not contribute significantly to the variation in disability.CONCLUSION: Disability attributed to symptoms from an increased IRD is explained primarily by the level of lumbopelvic pain but also by the degree of fear-avoidance beliefs and emotional distress.IMPACT: This study highlights pain intensity and psychological factors as crucial factors for understanding disability attributed to increased IRD.
|
|
| 36. |
- Eriksson, Erik, 1991-, et al.
(författare)
-
Dimensionering av momentskärmstativ
- 2013
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- På uppdrag av Saab ska fyra studenter vid Linköpings tekniska högskola designa och dimensionera ett momentskärmstativ till nya JAS39 Gripen E. På stativet fästs en skärmbehållare med en skärm, som används vid testflygning. Stativet sitter längst bak på planet, bakom sidorodret och ovanför stjärtkonen. Skärmen är en säkerhetsfunktion och kan skjutas ut och ge flygplanet ett stabiliserande tippmoment vid okontrollerade spinnfall som kan uppkomma vid högalfaflygning. Stativet ska klara av från uppdragsgivare givna lastfall och deformationskrav samtidigt som fokus skall ligga på viktreducering.Projektet började med konceptgenerering för att få fram ett grundkoncept att arbeta vidare med. Materialundersökningar genomfördes med hjälp av materialdatabasen CES EduPack 2012 för att hitta ett material med bättre egenskaper än det som använts i tidigare stativ. Utifrån materialet undersöktes även fogar, tillåtna initialsprickor samt knäckningsrisk. Olika tvärsnitt undersöktes och för att ta reda på deformationer och spänningar genomfördes FEM-analyser i Ansys Workbench 14.0. Utifrån analysresultaten förändrades stativets design tills det klarade kraven.Arbetet resulterade i ett fackverksstativ huvudsakligen uppbyggt av ihåliga kvadratiska balkar med yttermåtten 70 mm och innermåtten 63,8 mm. Maximala deformationen blir 53,1 mm, maximala spänningen 883 MPa och materialet som användes var titanlegeringen Ti-6Al-4V. Stativets balkar sammanfogas med lasersvets och det finns ingen risk för knäckning. Den tillåtna längden på en eventuell initialspricka är 0,7 mm för ytspricka och 0,9 mm för inre genomgående spricka. Det designade stativets slutvikt uppmättes till 60,5 kg.
|
|
| 37. |
|
|
| 38. |
- Eriksson, Henrik, 1973, et al.
(författare)
-
Exploring Quality Challenges and the Validity of Excellence Models
- 2016
-
Ingår i: International Journal of Operations & Production Management. - 0144-3577 .- 1758-6593. ; 36:10, s. 1201-1221
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose is to identify and explore important quality-related challenges facing organizations, and how current excellence models incorporate these challenges.Methodology: The article is based on a Delphi study in Swedish organizations, 49 challenges were generated and ranked according to importance. The top 10 ranked challenges were compared to the principles of four excellence models.Findings: The excellence models seem to still be relevant since their content matches many of the challenges identified. The MBNQA and the SIQ models were found to have the most comprehensive coverage, while the ISO model had limited coverage.Research Limitations/Implications: Three areas for further research were identified: 1) how QM can evolve in different contexts with varying needs in terms of adaptive and explorative capabilities, 2) the interfaces of QM and sustainability, and ways to understand how customers and stakeholders can be active contributors to improvements and 3) the roles of the owners and board of directors in QM, and how to organize and distribute responsibilities of the QM work.Practical and Social Implications: Three important challenges could be addressed in upcoming revisions of excellence models: 1) making QM a strategic issue for company owners; 2) involving customers in the improvement activities; and 3) developing processes that are robust, while still easily adaptable.Originality/Value: The Delphi study has identified upcoming challenges in the QM area based on input from 188 quality professionals.
|
|
| 39. |
- Eriksson, Ida, et al.
(författare)
-
Analysis of Lysosomal pH by Flow Cytometry Using FITC-Dextran Loaded Cells
- 2017
-
Ingår i: Lysosomes. - New York, NY : Humana Press. - 9781493969326 - 9781493969340 ; , s. 179-189
-
Bokkapitel (refereegranskat)abstract
- The acidic environment of the lysosomal lumen provides an optimal milieu for the acid hydrolases and is also essential for fusion/fission of endo-lysosomal compartments and sorting of cargo. Evidence suggests that maintaining lysosomal acidity is essential to avoid disease. In this chapter, we describe a protocol for analyzing the lysosomal pH in cultured cells using the fluorescent probe fluorescein isothiocyanate (FITC)-dextran together with a dual-emission ratiometric technique suitable for flow cytometry. Fluorescence-labeled dextran is endocytosed and accumulated in the lysosomal compartment. FITC shows a pH-dependent variation in fluorescence when analyzed at maximum emission wavelength and no variation when analyzing at the isosbestic point, thereby the ratio can be used to determine the lysosomal pH. A standard curve is obtained by equilibrating intralysosomal pH with extracellular pH using the ionophore nigericin. The protocol also includes information regarding procedures to induce lysosomal alkalinization and lysosomal membrane permeabilization.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Eriksson, Ida, 1985-
(författare)
-
Dealing with damaged lysosomes : Impact of lysosomal membrane stability in health and disease
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The lysosome is the main unit for degradation and plays important roles in various cellular processes, such as nutrient sensing, cholesterol regulation and cell death. Consequently, altered lysosomal function contributes to, or even causes, several diseases. Lysosomal membrane permeabilization (LMP) and release of lysosomal content to the cytosol can induce cell death, and is implicated in inflammation and neuronal decline in several neurodegenerative diseases. It has also emerged as a potential target in cancer therapy. Due to the detrimental effects of LMP, cells harbor several mechanisms to protect and prevent lysosomal membrane damage. The aim of this thesis was to elucidate how lysosomal membrane stability and repair mechanisms affect cell death and survival. We find that lysosomal cholesterol is upregulated in response to an increased load of reactive oxygen species in a Parkinson’s disease cell model, and that augmented cholesterol protects from LMP. However, cholesterol also induces accumulation of α-synuclein and inhibits lysosome-mediated degradation, which can destabilize the lysosomal membrane and accelerate the course of disease. Further, we demonstrate that lysosomal membrane damage is counteracted by a calcium-dependent repair mechanism to prevent LMP. Lysosomes damaged beyond repair are instead sequestered in an autophagosome and degraded by intact lysosomes in a process called lysophagy. As a result, small vesicles containing lysosomal membrane proteins are generated, which we believe are used to restore lysosomal function. We show that malignant cells are more sensitive to LMP, and that they differ in their activation of damage-response mechanisms compared to normal cells. Moreover, in malignant cells, the intracellular position of the lysosomes determines the susceptibility to lysosomal damage. Peripherally located lysosomes are less sensitive, and by relocating lysosomes to the perinuclear area in the cell, we can sensitize lysosomes to LMP induction. In summary, this thesis demonstrates the importance of damage-response mechanisms to protect from lysosomal membrane damage and maintain cellular function. It also indicates that targeting of lysosomal stability and repair is a potential therapeutic strategy in both neurodegenerative diseases and in cancer.
|
|
| 43. |
- Eriksson, Ida, et al.
(författare)
-
Determination of the detective quantum efficiency of gamma camera systems: a Monte Carlo study
- 2010
-
Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 139:1-3, s. 219-227
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present work was to investigate the validity of using the Monte Carlo technique for determining the detective quantum efficiency (DQE) of a gamma camera system and to use this technique in investigating the DQE behaviour of a gamma camera system and its dependency on a number of relevant parameters. The Monte Carlo-based software SIMIND, simulating a complete gamma camera system, was used in the present study. The modulation transfer function (MTF) of the system was determined from simulated images of a point source of (99m)Tc, positioned at different depths in a water phantom. Simulations were performed using different collimators and energy windows. The MTF of the system was combined with the photon yield and the sensitivity, obtained from the simulations, to form the frequency-dependent DQE of the system. As figure-of-merit (FOM), the integral of the 2D DQE was used. The simulated DQE curves agreed well with published data. As expected, there was a strong dependency of the shape and magnitude of the DQE curve on the collimator, energy window and imaging position. The highest FOM was obtained for a lower energy threshold of 127 keV for objects close to the detector and 131 keV for objects deeper in the phantom, supporting an asymmetric window setting to reduce scatter. The Monte Carlo software SIMIND can be used to determine the DQE of a gamma camera system from a simulated point source alone. The optimal DQE results in the present study were obtained for parameter settings close to the clinically used settings.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
- Eriksson, Ida, et al.
(författare)
-
Imidacloprid Induces Lysosomal Dysfunction and Cell Death in Human Astrocytes and Fibroblasts-Environmental Implication of a Clinical Case Report
- 2023
-
Ingår i: Cells. - : MDPI. - 2073-4409. ; 12:24
-
Tidskriftsartikel (refereegranskat)abstract
- Imidacloprid (IMI), a neonicotinoid insecticide, has potential cytotoxic and genotoxic effects on human and experimental models, respectively. While being an emerging environmental contaminant, occupational exposure and related cellular mechanisms are unknown. Herein, we were motivated by a specific patient case where occupational exposure to an IMI-containing plant protection product was associated with the diagnosis of Bell's palsy. The aim was to investigate the toxic effects and cellular mechanisms of IMI exposure on glial cells (D384 human astrocytes) and on human fibroblasts (AG01518). IMI-treated astrocytes showed a reduction in cell number and dose-dependent cytotoxicity at 24 h. Lower doses of IMI induced reactive oxygen species (ROS) and lysosomal membrane permeabilisation (LMP), causing apoptosis and autophagic dysfunction, while high doses caused significant necrotic cell death. Using normal fibroblasts, we found that IMI-induced autophagic dysfunction and lysosomal damage, activated lysophagy, and resulted in a compensatory increase in lysosomes. In conclusion, the observed IMI-induced effects on human glial cells and fibroblasts provide a possible link between IMI cytotoxicity and neurological complications observed clinically in the patient exposed to this neonicotinoid insecticide.
|
|
| 47. |
- Eriksson, Ida, et al.
(författare)
-
Impact of high cholesterol in a Parkinsons disease model: Prevention of lysosomal leakage versus stimulation of alpha-synuclein aggregation
- 2017
-
Ingår i: European Journal of Cell Biology. - : ELSEVIER GMBH, URBAN & FISCHER VERLAG. - 0171-9335 .- 1618-1298. ; 96:2, s. 99-109
-
Tidskriftsartikel (refereegranskat)abstract
- Parkinsons disease is characterized by accumulation of intraneuronal cytoplasmic inclusions, Lewy bodies, which mainly consist of aggregated alpha-synuclein. Controversies exist as to whether high blood cholesterol is a risk factor for the development of the disease and whether statin treatment could have a protective effect. Using a model system of BE(2)-M17 neuroblastoma cells treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), we found that MPP+-induced cell death was accompanied by cholesterol accumulation in a lysosomal-like pattern in pre-apoptotic cells. To study the effects of lysosomal cholesterol accumulation, we increased lysosomal cholesterol through pre-treatment with U18666A and found delayed leakage of lysosomal contents into the cytosol, which reduced cell death. This suggests that increased lysosomal cholesterol is a stress response mechanism to protect lysosomal membrane integrity in response to early apoptotic stress. However, high cholesterol also stimulated the accumulation of alpha-synuclein. Treatment with the cholesterol-lowering drug lovastatin reduced MPP+-induced cell death by inhibiting the production of reactive oxygen species, but did not prevent lysosomal cholesterol increase nor affect alpha-synuclein accumulation. Our study indicates a dual role of high cholesterol in Parkinsons disease, in which it acts both as a protector against lysosomal membrane permeabilization and as a stimulator of alpha-synuclein accumulation. (C) 2017 Elsevier GmbH. All rights reserved.
|
|
| 48. |
- Eriksson, Ida, et al.
(författare)
-
Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Melanoma
- 2023
-
Ingår i: Journal of Investigative Dermatology. - : ELSEVIER SCIENCE INC. - 0022-202X .- 1523-1747. ; 143:9, s. 1769-
-
Tidskriftsartikel (refereegranskat)abstract
- Lysosomes are central in cell homeostasis and participate in macromolecular degradation, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. In cancer, alterations in lysosomal function and spatial distribution may facilitate disease progression. In this study, we show enhanced lysosomal activity in malignant melanoma cells compared with that in normal human melanocytes. Most lysosomes show perinuclear location in melanocytes, while they are more dispersed in melanoma, with retained proteolytic activity and low pH also in the peripheral population. Rab7a expression is lower in melanoma cells than in melanocytes, and by increasing Rab7a, lysosomes are relocated to the perinuclear region in melanoma. Exposure to the lysosome-destabilizing drug L-leucyl-L-leucine methyl ester causes higher damage in the perinuclear subset of lysosomes in melanomas, whereas differences in subpopulation susceptibility cannot be found in melanocytes. Interestingly, melanoma cells recruit the endosomal sorting complex required for transport-III core protein CHMP4B, involved in lysosomal membrane repair, rather than initiate lysophagy. However, when the perinuclear lysosomal position is promoted by Rab7a overexpression or kinesore treatment, lysophagy is increased. In addition, Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.
|
|
| 49. |
- Eriksson, Ida, et al.
(författare)
-
Lysosomes in Cancer-At the Crossroad of Good and Evil
- 2024
-
Ingår i: Cells. - : MDPI. - 2073-4409. ; 13:5
-
Forskningsöversikt (refereegranskat)abstract
- Although it has been known for decades that lysosomes are central for degradation and recycling in the cell, their pivotal role as nutrient sensing signaling hubs has recently become of central interest. Since lysosomes are highly dynamic and in constant change regarding content and intracellular position, fusion/fission events allow communication between organelles in the cell, as well as cell-to-cell communication via exocytosis of lysosomal content and release of extracellular vesicles. Lysosomes also mediate different forms of regulated cell death by permeabilization of the lysosomal membrane and release of their content to the cytosol. In cancer cells, lysosomal biogenesis and autophagy are increased to support the increased metabolism and allow growth even under nutrient- and oxygen-poor conditions. Tumor cells also induce exocytosis of lysosomal content to the extracellular space to promote invasion and metastasis. However, due to the enhanced lysosomal function, cancer cells are often more susceptible to lysosomal membrane permeabilization, providing an alternative strategy to induce cell death. This review summarizes the current knowledge of cancer-associated alterations in lysosomal structure and function and illustrates how lysosomal exocytosis and release of extracellular vesicles affect disease progression. We focus on functional differences depending on lysosomal localization and the regulation of intracellular transport, and lastly provide insight how new therapeutic strategies can exploit the power of the lysosome and improve cancer treatment.
|
|
| 50. |
|
|
