| 1. |
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| 2. |
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| 3. |
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| 4. |
- Berger, Karoline, 1991, et al.
(author)
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Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer.
- 2023
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In: Cancers. - 2072-6694. ; 15:24
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Journal article (peer-reviewed)abstract
- Unraveling the complex network between cancer cells and their tumor microenvironment is of clinical importance, as it might allow for the identification of new targets for cancer treatment. Cytokines and growth factors secreted by various cell types present in the tumor microenvironment have the potential to affect the challenging subpopulation of cancer stem cells showing treatment-resistant properties as well as aggressive features. By using various model systems, we investigated how the breast cancer stem cell-initiating growth factor progranulin influenced the secretion of cancer-associated proteins. In monolayer cultures, progranulin induced secretion of several inflammatory-related cytokines, such as interleukin (IL)-6 and -8, in a sortilin-dependent manner. Further, IL-6 increased the cancer stem fraction similarly to progranulin in the breast cancer cell lines MCF7 and MDA-MB-231 monitored by the surrogate mammosphere-forming assay. In a cohort of 63 patient-derived scaffold cultures cultured with breast cancer cells, we observed significant correlations between IL-6 and progranulin secretion, clearly validating the association between IL-6 and progranulin also in human-based microenvironments. In conclusion, the interplay between progranulin and IL-6 highlights a dual breast cancer stem cell-promoting function via sortilin, further supporting sortilin as a highly relevant therapeutic target for aggressive breast cancer.
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| 5. |
- Eriksson, Helena, et al.
(author)
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Variation of satellite estimated LAI due to the impact of the ground vegetation cover
- 2005
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Conference paper (peer-reviewed)abstract
- The contribution of the understorey vegetation to the spectral reflectance from the top of a forest canopy was investigated by the use of a forest canopy reflectance model. Detailed field data, i.e. forest leaf area index (LAI), tree structural parameters like the height, diameter and crown length of the trees, and the composition, distribution and reflectance of the forest floor, was collected for some common forest types in southern Sweden and used as input data to the model. Results verify that the impact of the understorey to LAI estimates is of major importance and varies with both the understorey distribution and the forest properties.
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| 6. |
- Felixsson, Emma, et al.
(author)
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Horse chestnut extract contracts bovine vessels and affects human platelet aggregation through 5-HT(2A) receptors: an in vitro study
- 2010
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In: Phytotherapy Research. - : Wiley. - 0951-418X .- 1099-1573. ; 24:9, s. 1297-1301
-
Journal article (peer-reviewed)abstract
- Extract from seeds and bark of horse chestnut (Aesculus hippocastanum L) is used as an herbal medicine against chronic venous insufficiency. The effect and mechanism of action on veins, arteries, and platelets are not fully understood. The aim of this study was to investigate the effects and mechanisms of action of horse chestnut on the contraction of bovine mesenteric veins and arteries, and human platelet aggregation. Contraction studies showed that horse chestnut extract dose-dependently contracted both veins and arteries, with the veins being the most sensitive. Contraction of both veins and arteries were significantly inhibited by the 5-HT(2A) receptor antagonist ketanserin. No effect on contraction was seen with the cyclooxygenase inhibitor indomethacin, the alpha(1) receptor antagonist prazosin or the angiotensin AT(1) receptor antagonist saralasin neither in veins nor arteries. ADP-induced human platelet aggregation was significantly reduced by horse chestnut. A further reduction was seen with the extract in the presence of ketanserin. In conclusion, horse chestnut contraction of both veins and arteries is, at least partly, mediated through 5-HT(2A) receptors. Human platelet aggregation is reduced by horse chestnut. The clinical importance of these findings concerning clinical use, possible adverse effects, and drug interactions remains to be investigated. Copyright (c) 2010 John Wiley & Sons, Ltd.
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| 7. |
- Flores-Langarica, Adriana, et al.
(author)
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Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin
- 2018
-
In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:OCT
-
Journal article (peer-reviewed)abstract
- Systemic immunization with soluble flagellin (sFliC) from Salmonella Typhimurium induces mucosal responses, offering potential as an adjuvant platform for vaccines. Moreover, this engagement of mucosal immunity is necessary for optimal systemic immunity, demonstrating an interaction between these two semi-autonomous immune systems. Although TLR5 and CD103+CD11b+ cDC2 contribute to this process, the relationship between these is unclear in the early activation of CD4+ T cells and the development of antigen-specific B cell responses. In this work, we use TLR5-deficient mice and CD11c-cre.Irf4fl/fl mice (which have reduced numbers of cDC2, particularly intestinal CD103+CD11b+ cDCs), to address these points by studying the responses concurrently in the spleen and the mesenteric lymph nodes (MLN). We show that CD103+CD11b+ cDC2 respond rapidly and accumulate in the MLN after immunization with sFliC in a TLR5-dependent manner. Furthermore, we identify that whilst CD103+CD11b+ cDC2 are essential for the induction of primary T and B cell responses in the mucosa, they do not play such a central role for the induction of these responses in the spleen. Additionally, we show the involvement of CD103+CD11b+ cDC2 in the induction of Th2-associated responses. CD11c-cre.Irf4fl/fl mice showed a reduced primary FliC-specific Th2-associated IgG1 responses, but enhanced Th1-associated IgG2c responses. These data expand our current understanding of the mucosal immune responses promoted by sFliC and highlights the potential of this adjuvant for vaccine usage by taking advantage of the functionality of mucosal CD103+CD11b+ cDC2.
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| 8. |
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| 9. |
- Jonasson, Emma, 1987, et al.
(author)
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Identification of breast cancer stem cell related genes using functional cellular assays combined with single-cell RNA sequencing in MDA-MB-231 cells
- 2019
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In: Frontiers in Genetics. - : Frontiers Media SA. - 1664-8021. ; 10
-
Journal article (peer-reviewed)abstract
- Breast cancer tumors display different cellular phenotypes. A growing body of evidence points toward a population of cancer stem cells (CSCs) that is important for metastasis and treatment resistance, although the characteristics of these cells are incomplete. We used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of CSC properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing. We clustered the cells based on their gene expression profiles and identified three subpopulations, including a CSC-like population. The cell clustering into these subpopulations overlapped with the cellular enrichment approach applied. To molecularly define these groups, we identified genes differentially expressed between the three subpopulations which could be matched to enriched gene sets. We also investigated the transition process from CSC-like cells into more differentiated cell states. In the CSC population we found 14 significantly upregulated genes. Some of these potential breast CSC markers are associated to reported stem cell properties and clinical survival data, but further experimental validation is needed to confirm their cellular functions. Detailed characterization of CSCs improve our understanding of mechanisms for tumor progression and contribute to the identification of new treatment targets. © 2019 Jonasson, Ghannoum, Persson, Karlsson, Kroneis, Larsson, Landberg and Ståhlberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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| 10. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 11. |
- Landberg, Göran, 1963, et al.
(author)
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Characterization of cell-free breast cancer patient-derived scaffolds using liquid chromatography-mass spectrometry/mass spectrometry data and RNA sequencing data
- 2020
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In: Data in Brief. - : Elsevier BV. - 2352-3409. ; 31
-
Journal article (peer-reviewed)abstract
- Patient-derived scaffolds (PDSs) generated from primary breast cancer tumors can be used to model the tumor microenvironment in vitro . Patient-derived scaffolds are generated by repeated detergent washing, removing all cells. Here, we analyzed the protein composition of 15 decellularized PDSs using liquid chromatography-mass spectrometry/mass spectrometry. One hundred forty-three proteins were detected and their relative abundance was calculated using a reference sample generated from all PDSs. We performed heatmap analysis of all the detected proteins to display their expression patterns across different PDSs together with pathway enrichment analysis to reveal which processes that were connected to PDS protein composition. This protein dataset together with clinical information is useful to investigators studying the microenvironment of breast cancers. Further, after repopulating PDSs with either MCF7 or MDA-MB-231 cells, we quantified their gene expression profiles using RNA sequencing. These data were also compared to cells cultured in conventional 2D conditions, as well as to cells cultured as xenografts in immune-deficient mice. We investigated the overlap of genes regulated between these different culture conditions and performed pathway enrichment analysis of genes regulated by both PDS and xenograft cultures compared to 2D in both cell lines to describe common processes associated with both culture conditions. Apart from our described analyses of these systems, these data are useful when comparing different experimental model systems. Downstream data analyses and interpretations can be found in the research article "Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment" [1] . (C) 2020 The Authors. Published by Elsevier Inc.
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| 12. |
- Landberg, Göran, et al.
(author)
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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment
- 2020
-
In: Biomaterials. - : Elsevier Ltd. - 0142-9612 .- 1878-5905. ; 235
-
Journal article (peer-reviewed)abstract
- Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors
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| 13. |
- Persson, Emma, 1981-, et al.
(author)
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Effect of type 1 diabetes on school performance in a dynamic world : new analysis exploring Swedish register data
- 2019
-
In: Applied Economics. - : Taylor & Francis Group. - 0003-6846 .- 1466-4283. ; 51:24, s. 2606-2622
-
Journal article (peer-reviewed)abstract
- This paper investigates if the effect of type 1 diabetes mellitus (T1DM) on school performance, documented in prior research, has changed in more recent birth cohorts of children using national Swedish population register data. The issue is of interest because management and treatment of the disease have improved over the last decades and, furthermore, because of changes in the educational grading system. Despite these changes, data indicate a persistent negative effect of T1DM on compulsory and upper secondary school grades with a standardized effect size of −0.109 and −0.070, respectively, and the results appear only marginally smaller compared to earlier findings in cohorts completing school under the previous grading system. Moreover, the results are consistent for alternative model specifications and econometric estimation strategies. Whereas access to new treatment technologies and improved diabetes management strategies has reduced the burden of diabetes in daily life, the results from this study indicate that continued efforts are needed to improve the situation in school for children with T1DM to prevent potential long-term socio-economic consequences.
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| 14. |
- Persson, Emma, et al.
(author)
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Effect of Type 1 Diabetes on School Performance in a Dynamic World : New Analysis Exploring Swedish Register Data
- 2016
-
Other publication (other academic/artistic)abstract
- This paper investigates if the effect of type 1 diabetes mellitus (T1DM) on school performance has changed over time using national Swedish population register data. The issue is of interest because management and treatment of the disease have improved over the last decades and, furthermore, because of changes in the educational grading system. Despite these changes, data indicate a persistent negative effect of T1DM on compulsory and upper secondary school grades and the results appears similar to earlier findings on cohorts completing school under the previous grading system. Moreover, the results are robust to alternative model specifications and econometric estimation strategies. Whereas access to new treatment technologies and improved diabetes management strategies has reduced the burden of diabetes in daily life, the results from this study indicate that other trends have not implied a reduction, over time, in the impact of T1DM on school performance. This finding indicates that continued efforts are needed to improve the situation in school for children with T1DM to prevent potential long-term socioeconomic consequences.
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| 15. |
- Persson-Sjödin, Emma, et al.
(author)
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Relationship between body condition and vertical movement symmetry in 109 riding school horses
- 2023
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In: Comparative Exercise Physiology. - 1755-2540 .- 1755-2559. ; 19, s. 501-510
-
Journal article (peer-reviewed)abstract
- For riding schools, the health and function of their horses is paramount. Unfortunately, lameness and overweight are common problems in this population, and a causal relationship whereby increased body weight causes lameness is also possible. This observational field study investigated the relationship between body condition score (BCS) and motion movement asymmetries in riding school horses and also explored the relationships between BCS, movement asymmetry and subjectively scored willingness to work. Eight riding schools within 2.5 h by car from Uppsala, Sweden, were convenience-sampled and 3-24 horses from each were included in the study. Body condition was scored (scale 1-9) and vertical movement asymmetry data were collected in straight-line trot, using an inertial measurement unit system. Asymmetry parameters were calculated as the mean difference between local vertical displacement minima/maxima for the head/pelvis (HD/PD) between the two halves of the stride. A questionnaire was used to assess perceived willingness to work and energy level of the horses. The data were analysed with linear mixed models, t-tests and Mann-Whitney U-tests. A correlation was found between BCS and PDmin (P =0.03), an asymmetry parameter related to hindlimb weight-bearing lameness, where PDmin increased by 0.96 mm for each unit increase in BCS. Horses with vertical movement classified as symmetric had lower BCS than horses with movement classified as asymmetric (5.4 ± 0.4 vs 5.7 ± 0.6, P =0.04). Horses classed as overweight (BCS ≥ 6) scored lower on willingness to work (P <0.05) and energy level (P <0.01). These results indicate that the body condition of riding school horses may influence their function and the health of their locomotor apparatus. Further studies are required to identify the underlying mechanisms.
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| 16. |
- Sandén, Emma, et al.
(author)
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Aberrant immunostaining pattern of the CD24 glycoprotein in clinical samples and experimental models of pediatric medulloblastomas
- 2015
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In: Journal of Neuro-Oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 123:1, s. 1-13
-
Journal article (peer-reviewed)abstract
- The CD24 glycoprotein is a mediator of neuronal proliferation, differentiation and immune suppression in the normal CNS, and a proposed cancer biomarker in multiple peripheral tumor types. We performed a comparative analysis of CD24 gene expression in a large cohort of pediatric and adult brain tumors (n = 813), and further characterized protein expression in tissue sections (n = 39), primary brain tumor cultures (n = 12) and a novel orthotopic group 3 medulloblastoma xenograft model. Increased CD24 gene expression was demonstrated in ependymomas, medulloblastomas, anaplastic astrocytomas and glioblastomas, although medulloblastomas displayed higher expression than all other tumor entities. Preferential expression of CD24 in medulloblastomas was confirmed at protein level by immunostaining and computerized image analysis of cryosections. Morphologies and immunophenotyping of CD24(+) cells in tissue sections tentatively suggested disparate functions in different tumor subsets. Notably, protein staining of medulloblastoma cells was associated with prominent cytoplasmic and membranous granules, enabling rapid and robust identification of medulloblastoma cells in clinical tissue samples, as well as in experimental model systems. In conclusion, our results implicate CD24 as a clinically and experimentally useful medulloblastoma immunomarker. Although our results encourage further functional studies of CD24 as a potential molecular target in subsets of brain tumors, the promiscuous expression of CD24 in vivo highlights the importance of specificity in the future design of such targeted treatment.
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| 17. |
- Abzhandadze, Tamar, 1980, et al.
(author)
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Impact of pre-pandemic sick leave diagnoses on the length of COVID-19-related sick leave: a nationwide registry-based study
- 2023
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In: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 23:1
-
Journal article (peer-reviewed)abstract
- Background: The COVID-19 pandemic has caused difficulties and changes in many aspects of people’s health and lives. Although infection affected work capacity, during the first wave policies for sick leave due to COVID-19 were unclear. The aim of this study was to investigate the impact of sick leave diagnoses in the year before the COVID-19 diagnosis on sick leave duration due to COVID-19 in a nationwide non-hospitalised population. Methods: Data from three Swedish registries were analysed for sick leave commencing between 1 March and 31 August 2020, with a follow-up period of 4months. Sick leave due to COVID-19 was considered the number of days that sickness benefits were used and included at least one registered COVID-19 diagnosis. Sick leave in the year before COVID-19 diagnosis were categorised into five diagnostic groups and one reference group (participants without prior sick leave). Results: The study comprised 8935individuals who received sickness benefits due to COVID-19 in Sweden during the first pandemic wave (mean age 46.7years, 67% females, and 24% had diagnoses for sick leave in the year before COVID-19diagnosis). The duration of sick leave due to COVID-19 was significantly higher in the groups with prior sick leave owing to musculoskeletal system diseases (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 1.01–1.15); respiratory system diseases (OR: 1.22, 95% CI: 1.14–1.31); all other isolated diagnoses (OR: 1.08, 95% CI: 1.03–1.14); and multiple diagnoses (OR: 1.32, 95% CI: 1.21–1.43). Conclusions: The results of this nationwide registry-based study indicate that individuals with premorbid conditions are more prone to longer sick leave durations due to COVID-19. Prediction of sick leave duration during the first wave of the COVID-19 pandemic is complex and several factors played a role. © 2023, The Author(s).
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| 18. |
- Abzhandadze, Tamar, 1980, et al.
(author)
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Sick leave oneyear after COVID-19 infection: a nationwide cohort study during the first wave in Sweden.
- 2024
-
In: Scientific reports. - 2045-2322. ; 14:1
-
Journal article (peer-reviewed)abstract
- This study aimed to investigate the patterns of sick leave, as well as factors associated with sick leave due to COVID-19 during one year after the COVID-19 diagnosis, and sex-related aspects on sick leave. This nationwide study involved 11,902 individuals who received sickness benefits for COVID-19 during the first wave of the pandemic. Data from three Swedish registries were analyzed for sick leave that commenced between March 1 and August 31, 2020, with a follow-up period of 12months. Sick leave due to COVID-19 was counted as the number of days with sickness benefits and required to include at least one registered COVID-19 diagnosis. The median duration of sick leave was 35days, and 347 (2.9%) individuals continued their sick leave during the entire follow-up period. Furthermore, 1year later, the cumulative incidence of sick leave was slightly higher in males (3.5%) compared to females (2.7%). Older age, being single with no children, diagnosed with the virus, medium income level, history of sick leave, and need for inpatient care were significantly associated with a higher duration of sick leave due to COVID-19, both in the total population and when stratified by sex. These results indicated that three out of 100 (3%) patients were still on sick leave 1year after their COVID-19 diagnosis. Aspects regarding the importance of sick leave duration differed between males and females and comprised sociodemographic characteristics and need for inpatient care. The results indicated the complexity of sick leave due to COVID-19.
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| 19. |
- Agace, William, et al.
(author)
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How vitamin A metabolizing dendritic cells are generated in the gut mucosa.
- 2012
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In: Trends in Immunology. - : Elsevier BV. - 1471-4981 .- 1471-4906. ; 33, s. 42-48
-
Journal article (peer-reviewed)abstract
- CD103(+) dendritic cells (DCs) represent the major migratory DC population in the intestinal lamina propria and are believed to play an essential role in the initiation and regulation of mucosal adaptive immune responses. Small intestine (SI) CD103(+) DCs have an enhanced capacity to generate the vitamin A metabolite, retinoic acid, a property that underlies their ability to induce the gut homing receptors CC chemokine receptor 9 and α4β7 on responding T and B cells, and enhance forkhead box P3(+) T regulatory and IgA plasma cell differentiation in vitro. In this review, we discuss the environmental signals that appear to promote vitamin A metabolising activity in SI CD103(+) DCs in the steady state and thus which may contribute to driving the unique nature of SI immune responses.
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| 20. |
- Ahlberg, Erik, et al.
(author)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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In: Dagens nyheter (DN debatt). - 1101-2447.
-
Journal article (pop. science, debate, etc.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 21. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
-
In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Journal article (peer-reviewed)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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| 22. |
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| 23. |
- Almandoz-Gil, Leire, et al.
(author)
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In situ proximity ligation assay reveals co-localization of alpha-synuclein and SNARE proteins in murine primary neurons
- 2018
-
In: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 9
-
Journal article (peer-reviewed)abstract
- The aggregation of alpha-synuclein (alpha Syn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of aSyn is to promote the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between aSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA). Cortical primary neurons were cultured from either non-transgenic or transgenic mice expressing human aSyn with the A30P mutation under the Thy-1 promoter. With an antibody recognizing both mouse and human aSyn, a PLA signal indicating close proximity between aSyn and the three SNARE proteins was observed both in the soma and throughout the processes. No differences in the extent of PLA signals were seen between non-transgenic and transgenic neurons. With an antibody specific against human aSyn, the PLA signal was mostly located to the soma and was only present in a few cells. Taken together, in situ PLA is a method that can be used to investigate the co-localization of aSyn and the SNARE proteins in primary neuronal cultures
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| 24. |
- Andersson Granberg, Tobias, 1973-, et al.
(author)
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Predicting Volunteer Travel Time to Emergencies
- 2022
-
In: ISCRAM 2022 Conference Proceedings – 19th International Conference on Information Systems for Crisis Response and Management. - 9788284270999 ; , s. 44-54
-
Conference paper (peer-reviewed)abstract
- A model is developed, which can predict the travel time for volunteers that are dispatched as first responders to emergencies. Specifically, the case of lay responders to out of hospital cardiac arrest is studied. Positions from historical responses is used to estimate the real response times, which are used to train and evaluate the new travel time model. The new model considers the road network and the transport mode most likely used by the volunteers. The results for the new model are compared to a model used in an existing volunteer initiative. They show that the new model can make better predictions in 59.7% of the cases. This can be used directly as a base for improving the travel time estimates in existing volunteer initiatives, and to improve the input data to the continuously evolving volunteer resource management systems.
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| 25. |
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| 26. |
- Atiomo, William, et al.
(author)
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Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome
- 2017
-
In: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265. ; 87:5, s. 557-565
-
Journal article (peer-reviewed)abstract
- Objective: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC). Aim: To investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC. Design and Methods: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry in EC samples from a separate cohort (n = 91) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study. Results: We show for the first that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to nonmalignant endometrial tissue (P < .0001). Conclusions: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.
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| 27. |
- Bekiaris, Vasileios, et al.
(author)
-
Intestinal dendritic cells in the regulation of mucosal immunity.
- 2014
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In: Immunological Reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 260:1, s. 86-101
-
Research review (peer-reviewed)abstract
- The intestine presents a huge surface area to the outside environment, a property that is of critical importance for its key functions in nutrient digestion, absorption, and waste disposal. As such, the intestine is constantly exposed to dietary and microbial-derived foreign antigens, to which immune cells within the mucosa must suitably respond to maintain intestinal integrity, while also providing the ability to mount effective immune responses to potential pathogens. Dendritic cells (DCs) are sentinel immune cells that play a central role in the initiation and differentiation of adaptive immune responses. In the intestinal mucosa, DCs are located diffusely throughout the intestinal lamina propria, within gut-associated lymphoid tissues, including Peyer's patches and smaller lymphoid aggregates, as well as in intestinal-draining lymph nodes, including mesenteric lymph nodes. The recognition that dietary nutrients and microbial communities in the intestine influence both mucosal and systemic immune cell development and function as well as immune-mediated disease has led to an explosion of literature in mucosal immunology in recent years and a growing interest in the functionality of intestinal DCs. In the current review, we discuss recent findings from our group and others that have provided important insights regarding murine and human intestinal lamina propria DCs and highlighted marked developmental and functional heterogeneity within this compartment. A thorough understanding of the role these subsets play in the regulation of intestinal immune homeostasis and inflammation will help to define novel strategies for the treatment of intestinal pathologies and contribute to improved rational design of mucosal vaccines.
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| 28. |
- Bergerson, Emma, et al.
(author)
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Superior Outcome of Early ACL Reconstruction versus Initial Non-reconstructive Treatment With Late Crossover to Surgery A Study From the Swedish National Knee Ligament Registry
- 2022
-
In: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 50:4, s. 896-903
-
Journal article (peer-reviewed)abstract
- Background: Although comparable clinical and functional outcomes have been reported after nonsurgical and surgical anterior cruciate ligament (ACL) treatment, few studies have investigated the effects of early versus late ACL reconstruction with initial rehabilitation. Purpose: To determine patient-reported knee function in patients who initially undergo nonreconstructive treatment after an ACL injury but who later choose to undergo ACL reconstruction as compared with (1) patients undergoing ACL reconstruction close to the index injury and (2) patients treated nonreconstructively at 1 to 10 years of follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Results from the Knee injury and Osteoarthritis Outcome Score (KOOS) were extracted from the Swedish National Knee Ligament Registry for patients treated with nonreconstruction, early ACL reconstruction, and initial nonreconstruction but subsequent ACL reconstruction (crossover group). The KOOS4 (a mean of 4 KOOS subscales) was analyzed cross-sectionally at baseline and at the 1-, 2-, 5-, and 10-year follow-ups. Additionally, the Patient Acceptable Symptom State (PASS) was applied to all KOOS subscales from baseline to the 10-year follow-up. Results: A total of 1,074 crossover, 484 nonreconstruction, and 20,352 early ACL reconstruction cases were included. The crossover group reported lower KOOS4 values than the group undergoing early ACL reconstruction at baseline and at all follow-ups (mean difference [95% CI]): baseline, -6.5 (-8.0 to -5.0); 1 year, -9.3 (-10.9 to -7.7); 2 years, -4.8 (-6.3 to -3.2); 5 years, -6.1 (-8.8 to -3.4); and 10 years, -10.9 (-16.3 to -5.2). Additionally, a smaller proportion of the crossover cohort achieved a PASS on KOOS subscales at baseline and through the 1-, 2-, 5-, and 10-year follow-ups as compared with the early ACL reconstruction cohort. No differences were observed between crossover and nonreconstruction cases on either the KOOS4 or the PASS at any follow-up. Conclusion: A greater proportion of patients treated with early ACL reconstruction reported acceptable knee function and superior overall knee function as compared with patients who decided to cross over from nonreconstructive treatment to ACL reconstruction.
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| 29. |
- Berglund, Lisa, et al.
(author)
-
A genecentric Human Protein Atlas for expression profiles based on antibodies
- 2008
-
In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 7:10, s. 2019-2027
-
Research review (peer-reviewed)abstract
- An attractive path forward in proteomics is to experimentally annotate the human protein complement of the genome in a genecentric manner. Using antibodies, it might be possible to design protein-specific probes for a representative protein from every protein-coding gene and to subsequently use the antibodies for systematical analysis of cellular distribution and subcellular localization of proteins in normal and disease tissues. A new version (4.0) of the Human Protein Atlas has been developed in a genecentric manner with the inclusion of all human genes and splice variants predicted from genome efforts together with a visualization of each protein with characteristics such as predicted membrane regions, signal peptide, and protein domains and new plots showing the uniqueness (sequence similarity) of every fraction of each protein toward all other human proteins. The new version is based on tissue profiles generated from 6120 antibodies with more than five million immunohistochemistry-based images covering 5067 human genes, corresponding to approximately 25% of the human genome. Version 4.0 includes a putative list of members in various protein classes, both functional classes, such as kinases, transcription factors, G-protein-coupled receptors, etc., and project-related classes, such as candidate genes for cancer or cardiovascular diseases. The exact antigen sequence for the internally generated antibodies has also been released together with a visualization of the application-specific validation performed for each antibody, including a protein array assay, Western blot analysis, immunohistochemistry, and, for a large fraction, immunofluorescence-based confocal microscopy. New search functionalities have been added to allow complex queries regarding protein expression profiles, protein classes, and chromosome location. The new version of the protein atlas thus is a resource for many areas of biomedical research, including protein science and biomarker discovery.
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| 30. |
- Björklund, Emmelie, et al.
(author)
-
Involvement of Fatty Acid Amide Hydrolase and Fatty Acid Binding Protein 5 in the Uptake of Anandamide by Cell Lines with Different Levels of Fatty Acid Amide Hydrolase Expression: A Pharmacological Study
- 2014
-
In: PLOS ONE. - : PLoS ONE. - 1932-6203. ; 9:7, s. e103479-
-
Journal article (peer-reviewed)abstract
- Background:The endocannabinoid ligand anandamide (AEA) is removed from the extracellular space by a process ofcellular uptake followed by metabolism. In many cells, such as the RBL-2H3 cell line, inhibition of FAAH activity reduces theobserved uptake, indicating that the enzyme regulates uptake by controlling the intra- : extracellular AEA concentrationgradient. However, in other FAAH-expressing cells, no such effect is seen. It is not clear, however, whether these differencesare methodological in nature or due to properties of the cells themselves. In consequence, we have reinvestigated the roleof FAAH in gating the uptake of AEA.Methodology/Principal Findings: The effects of FAAH inhibition upon AEA uptake were investigated in four cell lines: AT1rat prostate cancer, RBL-2H3 rat basophilic leukaemia, rat C6 glioma and mouse P19 embryonic carcinoma cells. SemiquantitativePCR for the cells and for a rat brain lysate confirmed the expression of FAAH. No obvious expression of atranscript with the expected molecular weight of FLAT was seen. FAAH expression differed between cells, but all four couldaccumulate AEA in a manner inhibitable by the selective FAAH inhibitor URB597. However, there was a difference in thesensitivities seen in the reduction of uptake for a given degree of FAAH inhibition produced by a reversible FAAH inhibitor,with C6 cells being more sensitive than RBL-2H3 cells, despite rather similar expression levels and activities of FAAH. Thefour cell lines all expressed FABP5, and AEA uptake was reduced in the presence of the FABP5 inhibitor SB-FI-26, suggestingthat the different sensitivities to FAAH inhibition for C6 and RBL2H3 cells is not due to differences at the level of FABP-5.Conclusions/Significance: When assayed using the same methodology, different FAAH-expressing cells display differentsensitivities of uptake to FAAH inhibition.
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| 31. |
- Björnerås, Caroline, et al.
(author)
-
High sulfate concentration enhances iron mobilization from organic soil to water
- 2019
-
In: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 144:3, s. 245-259
-
Journal article (peer-reviewed)abstract
- Widespread increases in iron (Fe) concentrations are contributing to ongoing browning of northern freshwaters, but the driver/s behind the trends are not known. Fe mobilization in soils is known to be controlled by redox conditions, pH, and DOC availability for complexation. Moreover, high sulfate concentrations have been suggested to constrain Fe in transition from soil to water, and declining sulfate deposition to have the opposite effect. We studied the effect of these Fe mobilization barriers in a microcosm experiment, applying high (peak S deposition) and low (present day) sulfate treatments and oxic versus anoxic conditions to boreal (O horizon) soil slurries. We hypothesized that anoxic conditions would favor Fe release. On the contrary we expected high sulfate concentrations to suppress Fe mobility, through FeS formation or by lowering pH and thereby DOC concentrations. Anoxia had positive effects on both Fe and DOC concentrations in solution. Contrasting with our hypothesis, Fe concentrations were enhanced at high sulfate concentrations, i.e. increasing acidity in high sulfate treatments appeared to promote Fe mobilization. Establishment of the basidiomycete fungus Jaapia ochroleuca in the oxic treatments 44 days into the experiment had a major impact on Fe mobilization by increasing total Fe concentrations in solution. Thus, anoxia and acidity, along with fungi mediated mobilization, were important in controlling Fe release from soil to the aqueous phase. While Fe is often assumed to precipitate as Fe(oxy)hydroxides in the transition from anoxic to oxic water in the riparian zone, Fe from anoxic treatments remained in solution after introduction of oxygen. Our results do not support reduced atmospheric S deposition as a driver behind increasing Fe concentrations in boreal freshwaters, but confirm the importance of reducing conditions—which may be enhanced by higher soil temperature and moisture—for mobilization of Fe across the terrestrial-aquatic interphase.
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| 32. |
- Björnerås, Caroline, et al.
(author)
-
Sediment Records Shed Light on Drivers of Decadal Iron Concentration Increase in a Boreal Lake
- 2022
-
In: Journal of Geophysical Research - Biogeosciences. - : American Geophysical Union (AGU). - 2169-8953 .- 2169-8961. ; 127:3
-
Journal article (peer-reviewed)abstract
- Increasing iron (Fe) concentrations are found in lakes on a wide geographical scale but exact causes are still debated. The observed trends might result from increased Fe loading from the terrestrial catchment, but also from changes in how Fe distributes between the water column and the sediments. To get a better understanding of the causes we investigated whether there has been any change in the sediment formation of Fe sulfides (FeS) as an Fe sink in response to declining atmospheric sulfur (S) deposition during recent decades. For our study, we chose Lake Bolmen in southern Sweden, a lake for which we confirmed that Fe concentrations in the water column have strongly increased along with water color during 1966-2018. Our investigations showed that Fe accumulation and speciation varied independently of S accumulation patterns in the Lake Bolmen sediment record. Thus, we were not able to relate the positive trend in Fe concentrations to reduced FeS binding in the sediments. Furthermore, we found that Fe accumulation rates increased along with lake water Fe concentrations, indicating that increased catchment loading rather than a change in the distribution between the sediments and the water column has driven the increase in Fe concentrations. The increased loading may be due to land-use change in the form of an extensive expansion of coniferous forest during the past century. Altered forest management practices and increased precipitation may have led to enhanced weathering and erosion of organic soil layers under aging coniferous forest.
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| 33. |
- Björnerås, Caroline, et al.
(author)
-
The lake as an iron sink - new insights on the role of iron speciation
- 2021
-
In: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 584
-
Journal article (peer-reviewed)abstract
- The solubility and behavior of iron (Fe) in natural waters is tightly linked to Fe speciation, and Fe speciation likely influences how Fe distributes between the water column and sediments. In this study, the function of a lake as an Fe sink, with focus on the role of Fe speciation, was assessed for Lake Bolmen in southern Sweden. We found that a large fraction of the Fe flowing in to the lake was efficiently lost by sedimentation in the lake basin. Fe in inflowing water was a mix of organically complexed mononuclear Fe, Fe-(oxy)hydroxides and Fe-bearing clays, while surface sediments were composed of Fe-(oxy)hydroxides, Fe-bearing clays, Fe-bearing silicates and Fe sulfides. The absence of organically complexed Fe in the surface sediments indicates that the lake is mainly a sink for minerogenic fractions. Furthermore, while lakes are considered to be sinks of Fe, it has been suggested that this function may be impaired by increasing precipitation and consequently shorter water residence time. In this study there were large within- and between-year variations in precipitation and Fe concentrations. However, rather than smaller Fe losses to the sediments during wet years, within-lake losses tended to be larger due to higher loading of Fe from the catchment. Thus, forecasted increases in precipitation may result in enhanced catchment export and Fe loading to lakes, and subsequently enhanced Fe sequestration in sediments.
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| 34. |
- Blasi, Maria, et al.
(author)
-
Historical and citizen-reported data show shifts in bumblebee phenology over the last century in Sweden
- 2023
-
In: Biodiversity and Conservation. - : Springer Science and Business Media LLC. - 0960-3115 .- 1572-9710. ; 32:5, s. 1523-1547
-
Journal article (peer-reviewed)abstract
- Bumblebees are a key taxon contributing to the provision of crop pollination and ecosystem functioning. However, land use and climate change are two of the main factors causing bee decline across the world. In this study, we investigated how the flight period of bumblebee spring queens has shifted over the last century in Sweden, and to what extent such shifts depended on climate change, landscape context, latitude, and the phenology of bumblebee species. We studied ten species of bumblebees and used observations from museum specimens covering 117 years from the southernmost region in Sweden (Scania), combined with citizen-reported observations during the past 20 years across Sweden. We found that the flight period of bumblebees has advanced by 5 days on average during the last 20 years across Sweden. In the agriculture-dominated region of Scania, we found that in the late 2010s bumblebee spring queen activity in simplified landscapes had advanced by on average 14 days, compared to 100 years ago. In addition, in simplified landscapes the flight period of early species was significantly earlier compared to in complex landscapes. Our results provide knowledge on the intraspecific variation of phenological traits, indicating that early species (often common species) exhibit a higher plastic response to the environment, which may facilitate adaptation to both climate and landscape changes, compared to the late species of which many are declining.
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| 35. |
- Brechter, Anna Bernhold, et al.
(author)
-
Kinin B1 and B2 receptor expression in osteoblasts and fibroblasts is enhanced by interleukin-1 and tumour necrosis factor-alpha. Effects dependent on activation of NF-kappaB and MAP kinases.
- 2008
-
In: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 43:1, s. 72-83
-
Journal article (peer-reviewed)abstract
- Pro-inflammatory mediators formed by the kallikrein-kinin system can stimulate bone resorption and synergistically potentiate bone resorption induced by IL-1 and TNF-alpha. We have shown that the effect is associated with synergistically enhanced RANKL expression and enhanced prostaglandin biosynthesis, due to increased cyclooxygenase-2 expression. In the present study, the effects of osteotropic cytokines and different kinins on the expression of receptor subtypes for bradykinin (BK), des-Arg10-Lys-BK (DALBK), IL-1beta and TNF-alpha have been investigated. IL-1beta and TNF-alpha enhanced kinin B1 and B2 receptor binding in the human osteoblastic cell line MG-63 and the mRNA expression of B1 and B2 receptors in MG-63 cells, human gingival fibroblasts and intact mouse calvarial bones. Kinins did not affect mRNA expression of IL-1 or TNF receptors. EMSA showed that IL-1beta and TNF-alpha activated NF-kappaB and AP-1 in MG-63 cells. IL-1beta stimulated NF-kappaB via a non-canonical pathway (p52/p65) and TNF-alpha via the canonical pathway (p50/p65). Activation of AP-1 involved c-Jun in both IL-1beta and TNF-alpha stimulated cells, but c-Fos only in TNF-alpha stimulated cells. Phospho-ELISA and Western blots showed that IL-1beta activated JNK and p38, but not ERK 1/2 MAP kinase. Pharmacological inhibitors showed that NF-kappaB, p38 and JNK were important for IL-1beta induced stimulation of B1 receptors, and NF-kappaB and p38 for B2 receptors. p38 and JNK were important for TNF-alpha induced stimulation of B1 receptors, whereas NF-kappaB, p38 and JNK were involved in TNF-alpha induced expression of B2 receptors. These data show that IL-1beta and TNF-alpha upregulate B1 and B2 receptor expression by mechanisms involving activation of both NF-kappaB and MAP kinase pathways, but that signal transduction pathways are different for IL-1beta and TNF-alpha. The enhanced kinin receptor expression induced by the pro-inflammatory cytokines IL-1beta and TNF-alpha might be one important mechanism involved in the synergistic enhancement of prostaglandin formation caused by co-treatment with kinins and one of the two cytokines. These mechanisms might help to explain the enhanced bone resorption associated with inflammatory disorders, including periodontitis and rheumatoid arthritis.
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| 36. |
- Burguillos Garcia, Miguel, et al.
(author)
-
Microglia-Secreted Galectin-3 Acts as a Toll-like Receptor 4 Ligand and Contributes to Microglial Activation.
- 2015
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 10:9, s. 1626-1638
-
Journal article (peer-reviewed)abstract
- Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations in neuroinflammatory diseases. Although the role of toll-like receptor 4 (TLR4) in microglia's inflammatory response is fully acknowledged, little is known about endogenous ligands that trigger TLR4 activation. Here, we report that galectin-3 (Gal3) released by microglia acts as an endogenous paracrine TLR4 ligand. Gal3-TLR4 interaction was further confirmed in a murine neuroinflammatory model (intranigral lipopolysaccharide [LPS] injection) and in human stroke subjects. Depletion of Gal3 exerted neuroprotective and anti-inflammatory effects following global brain ischemia and in the neuroinflammatory LPS model. These results suggest that Gal3-dependent-TLR4 activation could contribute to sustained microglia activation, prolonging the inflammatory response in the brain.
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| 37. |
- Burzio, Cecilia, 1991, et al.
(author)
-
Removal of organic micropollutants in the biological units of a Swedish wastewater treatment plant
- 2021
-
In: IOP Conference Series: Materials Science and Engineering. - 1757-8981 .- 1757-899X. ; 1209
-
Conference paper (peer-reviewed)abstract
- The present study investigates the presence and removal of target organic micropollutants in a large Swedish wastewater treatment plant designed for nutrient removal including activated sludge, trickling filters, nitrifying moving bed biofilm reactors (MBBRs) and post-denitrifying MBBRs. A total of 28 organic micropollutants were analysed, at concentrations ranging from few ng/L to µg/L, in the influent and effluent of the different biological reactors in two sampling campaigns. The observed micropollutant removal efficiencies of the wastewater treatment plant varied from insignificant (< 20%) to high (> 90%) between compounds. The activated sludge reactor, being the first in line, contributed to most of the removal from the water phase. Additional removal of a few compounds was observed in the biofilm units, but most of the persistent compounds remained stable through all biological treatments.
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| 38. |
- Byström, Anna, et al.
(author)
-
Lateral movement of the saddle relative to the equine spine in rising and sitting trot on a treadmill
- 2018
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13
-
Journal article (peer-reviewed)abstract
- Saddle slip, defined as a progressive lateral displacement of the saddle during ridden exercise, has recently been given attention in the scientific press as a potential sign of lameness. The aim of this study was to objectively quantify the normal lateral movement (oscillations) of the saddle relative to the horse in non-lame horses, and associate this movement to the movements of the horse and rider. Data from seven Warmblood dressage horses competing at Grand Prix (n = 6) or FEI Intermediate (n = 1) level, ridden by their usual riders, were used. Simultaneous kinetic, kinematic and saddle pressure measurements were conducted during sitting and rising trot on a force-measuring treadmill. The maximum lateral movement of the caudal part of the saddle relative to the horse's spine (MAX) was determined for each diagonal step. A mixed model was applied, with MAX as outcome, and T6 and S3 vertical position, rigid body rotation angles (roll, pitch, yaw) of the horse's and rider's pelvis, vertical ground reaction forces, saddle force, and rider position (rising in rising trot, sitting in rising trot or sitting in sitting trot) as explanatory variables. The least square means for MAX were 14.3 (SE 4.7) mm and 23.9 (SE 4.7) mm for rising and sitting in rising trot, and 20.3 (SE 4.7) mm for sitting trot. A 10 mm increase in maximum pelvic height at push off increased MAX by 1.4 mm (p<0.0001). One degree increase in rider pelvis roll decreased MAX 1.1 mm, and one degree increase in rider pelvis yaw increased MAX 0.7 mm (both p<0.0001). The linear relationships found between MAX and movements of both horse and rider implies that both horse and rider movement asymmetries are reflected in the lateral movements or oscillations of the saddle in non-lame horses.
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| 39. |
- Castresana-Aguirre, Miguel, et al.
(author)
-
PathBIX—a web server for network-based pathway annotation with adaptive null models
- 2021
-
In: Bioinformatics Advances. - : Oxford University Press (OUP). - 2635-0041. ; 1:1
-
Journal article (peer-reviewed)abstract
- Motivation: Pathway annotation is a vital tool for interpreting and giving meaning to experimental data in life sciences. Numerous tools exist for this task, where the most recent generation of pathway enrichment analysis tools, network-based methods, utilize biological networks to gain a richer source of information as a basis of the analysis than merely the gene content. Network-based methods use the network crosstalk between the query gene set and the genes in known pathways, and compare this to a null model of random expectation.Results: We developed PathBIX, a novel web application for network-based pathway analysis, based on the recently published ANUBIX algorithm which has been shown to be more accurate than previous network-based methods. The PathBIX website performs pathway annotation for 21 species, and utilizes prefetched and preprocessed network data from FunCoup 5.0 networks and pathway data from three databases: KEGG, Reactome, and WikiPathways.
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| 40. |
- Cipriano, Mariateresa, et al.
(author)
-
The influence of monoacylglycerol lipase inhibition upon the expression of epidermal growth factor receptor in human PC-3 prostate cancer cells.
- 2014
-
In: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 7, s. 441-447
-
Journal article (peer-reviewed)abstract
- Background: It has been reported that direct activation of the cannabinoid CB1 receptor in epidermal growth factor (EGR)-stimulated PC-3 prostate cancer cells results in an anti-proliferative effect accompanied by a down-regulation of EGF receptors (EGFR). In the present study, we investigated whether similar effects are seen following inhibition of the endocannabinoid hydrolytic enzyme monoacylglycerol lipase (MGL).Results: CB1 receptor expression levels were found to differ greatly between two experimental series conducted using PC-3 cells. The monoacylglycerol lipase inhibitor JZL184 increased levels of 2-arachidonoylglycerol in the PC-3 cells without producing changes in the levels of anandamide and related N-acylethanolamines. In the first series of experiments, JZL184 produced a small mitogenic effect for cells that had not been treated with EGF, whereas an anti-proliferative effect was seen for EGF-treated cells. An anti-proliferative effect for the EGF-treated cells was also seen with the CB receptor agonist CP55,940. In the second batch of cells, there was an interaction between JZL184 and CB1 receptor expression densities in linear regression analyses with EGFR expression as the dependent variable.Conclusions: Inhibition of MGL by JZL184 can affect EGFR expression. However, the use in our hands of PC-3 cells as a model to investigate the therapeutic potential of MGL inhibitors and related compounds is compromised by their variability of CB1 receptor expression.
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| 41. |
- Conaway, H Herschel, et al.
(author)
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Retinoids inhibit differentiation of hematopoietic osteoclast progenitors.
- 2009
-
In: The FASEB journal. - Bethesda, Md. : Wiley. - 1530-6860 .- 0892-6638. ; 23:10, s. 3526-38
-
Journal article (peer-reviewed)abstract
- Whether vitamin A promotes skeletal fragility, has no effect on fracture rate, or protects against bone loss is unclear. In the present study, effects of retinoids on osteoclast differentiation in cultured mouse bone marrow cells (BMCs), bone marrow macrophages (BMMs), spleen cells, and RAW264.7 cells were evaluated by analyzing osteoclast formation and expression of genes important in signal transduction and osteoclast function. All-trans-retinoic acid (ATRA) did not stimulate osteoclastogenesis in BMCs, but inhibited hormone and RANKL-induced gene expression and formation of osteoclasts. In BMMs, spleen cells, and RAW264.7 cells, osteoclast differentiation and formation stimulated by M-CSF/RANKL were inhibited (IC(50) = 0.3 nM) by ATRA. The effect was exerted at an early step of RANKL-induced differentiation. ATRA also abolished increases of the transcription factors c-Fos and NFAT2 stimulated by RANKL and suppressed down-regulation of the antiosteoclastogenic transcription factor MafB. By comparing effects of several compounds structurally related to ATRA, as well as by using receptor antagonists, evaluation pointed to inhibition being mediated by RARalpha, with no involvement of PPARbeta/delta. The results suggest that activation of RARalpha by retinoids in myeloid hematopoietic precursor cells decreases osteoclast formation by altering expression of the transcription factors c-Fos, NFAT2, and MafB.
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| 42. |
- Conaway, H Herschel, et al.
(author)
-
Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor.
- 2011
-
In: The Journal of biological chemistry. - 1083-351X .- 0021-9258. ; 286:36, s. 31425-36
-
Journal article (peer-reviewed)abstract
- Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RARα/β/γ) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RARα enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RARβ/γ or RARγ had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RARα antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on (45)Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RARα receptors, a response that can be inhibited by monomeric GR.
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| 43. |
- Dobsicek Trefna, Hana, 1979, et al.
(author)
-
Antenna Applicator for Microwave Hyperthermia Treatment of Pediatric Brain Cancer
- 2014
-
In: 8th European Conference on Antennas and Propagation, EuCAP 2014, The Hague, The Netherlands 6-11 April 2014. - 9788890701849
-
Conference paper (other academic/artistic)abstract
- A novel antenna applicator for microwave hyperthermia allowing treatment of deep brain tumors is proposed. The applicator consists of up to 16 antennas placed around the head in a helmet-like set-up and operates at a frequency range of 430-1000~MHz. The self-grounded bow-tie antennas are housed in a molded plastic enclosure with the shape of a truncated cone. The inner space of the enclosure is filled with distilled water. The antennas are attached to a perimetric water bolus with a thickness of 2 cm and aligned with the head shape. The focusing ability of the applicator was investigated on a homogeneous SAM model and on a model of a 13-year old patient containing a spherical tumor of 2 cm radius. Two different tumor positions were investigated: the right frontal lobe and the central brain. The obtained SAR distributions are favorable, although a relatively high level of energy is also absorbed on the surface of the body. This heating is however not expected to cause problems as it can be cooled by blood perfusion and water bolus. Our results show that focused microwave heating in the brain is feasible and warrants further verification on phantoms.
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| 44. |
- Ekberg, Christian, 1967, et al.
(author)
-
The structures of CyMe4-BTBP complexes of americium(III) and europium(III) in solvents used in solvent extraction, explaining their separation properties
- 2015
-
In: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9226 .- 1477-9234. ; 44:42, s. 18395-18402
-
Journal article (peer-reviewed)abstract
- Separation of trivalent actinoid (An(III)) and lanthanoid (Ln(III)) ions is extremely challenging due to their similar ionic radii and chemical properties. Poly-aromatic nitrogen compounds acting as tetradentate chelating ligands to the metal ions in the extraction, have the ability to sufficiently separate An(III) from Ln(III). One of these compounds, 6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzol[1,2,4]triazin-3-y l)-[2,2]bipyridine, CyMe4-BTBP, has proven to be resistant towards acidic environments and strong radiation from radioactive decomposition. EXAFS studies of the dicomplexes of CyMe4-BTBP with americium(III) and europium(III) in nitrobenzene, cyclohexanone, 1-hexanol, 1-octanol and malonamide (DMDOHEMA) in 1-octanol have been carried out to get a deeper understanding of the parameters responsible for the separation. The predominating complexes independent of solvent used are [Am(CyMe4-BTBP)(2)(NO3)](2+) and [Eu(CyMe4-BTBP)(2)](3+), respectively, which are present as outer-sphere ion-pairs with nitrate ions in the studied solvents with low relative permittivity. The presence of a nitrate ion in the first coordination sphere of the americium(III) complex compensates the charge density of the complex considerably in comparison when only outer-sphere ion-pairs are formed as for the [Eu(CyMe4-BTBP)(2)](3+) complex. The stability and solubility of a complex in a solvent with low relative permittivity increase with decreasing charge density. The [Am(CyMe4-BTBP)(2)(NO3)](2+) complex will therefore be increasingly soluble and stabilized over the [Eu(CyMe4-BTBP)(2)](3+) complex in solvents with decreasing relative permittivity of the solvent. The separation of americium(III) from europium(III) with CyMe4-BTBP as extraction agent will increase with decreasing relative permittivity of the solvent, and thereby also with decreasing solubility of CyMe4-BTBP. The choice of solvent is therefore a balance of a high separation factor and sufficient solubility of the CyMe4-BTBP ligand.
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| 45. |
- Ekblad, Lars, et al.
(author)
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Cell-line-specific stimulation of tumor cell aggressiveness by wound healing factors - a central role for STAT3
- 2013
-
In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13, s. 33-
-
Journal article (peer-reviewed)abstract
- Background: Local recurrence is a major factor affecting survival after treatment for head and neck squamous cell carcinoma (HNSCC). It is possible that the normal processes involved in wound healing after surgical removal of a primary tumor can boost the regrowth of residual cancer cells, thereby contributing to the recurrent growth. In this work, we collected human wound fluids and used them to investigate the effect of wound healing factors on HNSCC cell lines in vitro. Methods: Wound fluids were collected from thyroidectomized patients diagnosed with benign disease and were included in assays of cell proliferation, migration, cell scattering, and invasion. The involvement of intracellular signaling pathways and membrane receptors were investigated by western blotting and the inclusion of specific inhibitors. Results: One out of four cell lines was greatly stimulated in proliferation, migration, cell scattering, and invasion by the addition of wound fluid as compared with addition of fetal bovine or human serum. These effects were accompanied by a sharp increase in activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 activation abolished the wound fluid response, showing that STAT3 plays an important role in the wound healing response. Several of the observed phenotypic changes were epithelial-to-mesenchymal transition (EMT)-like, but the appropriate changes were not seen in any of the EMT markers investigated. The involvement of c-Met or epidermal growth factor receptor family members was excluded, while the interleukin-6 receptor was found to be partly responsible for the activation of STAT3. Conclusions: In conclusion, we found cell-line-specific effects of wound healing factors on HNSCC, setting the stage for therapy development and predictive opportunities.
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| 46. |
- Ekström, Eva-Charlotte, et al.
(author)
-
Effects of prenatal micronutrient and early food supplementation on metabolic status of the offspring at 4.5 years of age. The MINIMat randomized trial in rural Bangladesh.
- 2016
-
In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:5, s. 1656-1667
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Journal article (peer-reviewed)abstract
- BACKGROUND: Fetal nutritional insults may alter the later metabolic phenotype. We hypothesized that early timing of prenatal food supplementation and multiple micronutrient supplementation (MMS) would favourably influence childhood metabolic phenotype.METHODS: Pregnant women recruited 1 January to 31 December 2002 in Matlab, Bangladesh, were randomized into supplementation with capsules of either 30 mg of iron and 400 μg of folic acid, 60 mg of iron and 400 μg of folic acid, or MMS containing a daily allowance of 15 micronutrients, and randomized to food supplementation (608 kcal) either with early invitation (9 weeks' gestation) or usual invitation (at 20 weeks). Their children (n = 1667) were followed up at 4.5 years with assessment of biomarkers of lipid and glucose metabolism, inflammation and oxidative stress.RESULTS: Children in the group with early timing of food supplementation had lower cholesterol (difference -0.079 mmol/l, 95% confidence interval (CI) -0.156; -0.003), low-density lipoprotein (LDL) (difference -0.068 mmol/l, 95% CI -0.126; -0.011) and ApoB levels (difference -0.017 g/l, 95% CL -0.033; -0.001). MMS supplementation resulted in lower high-density lipoprotein (HDL) (difference -0.028 mmol/l, 95% CL -0.053; -0.002), lower glucose (difference -0.099 mmol/l, 95% CL -0.179; -0.019) and lower insulin-like growth factor 1 (IGF-1) (difference on log scale -0.141 µg/l, 95% CL -0.254; -0.028) than 60 mg iron and 400 μg folic acid. There were no effects on markers of inflammation or oxidative stress.CONCLUSIONS: Findings suggest that in a population where malnutrition is prevalent, nutrition interventions during pregnancy may modify the metabolic phenotype in the young child that could have consequences for later chronic disease risks.
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| 47. |
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| 48. |
- Eneqvist, Ted, et al.
(author)
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Spinal surgery and the risk of reoperation after total hip arthroplasty : a cohort study based on Swedish spine and hip arthroplasty registers
- 2024
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In: Acta Orthopaedica. - : Medical Journals Sweden. - 1745-3674 .- 1745-3682. ; 95, s. 12-18
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Journal article (peer-reviewed)abstract
- Background and purpose - Studies suggest increased revision risk of total hip arthroplasty (THA) in individuals with lumbar spinal fusion, but studies including non-fused individuals are lacking. We aimed to investigate whether individuals undergoing lumbar spinal stenosis surgery with or without fusion are at an increased risk of reoperation before or after THA.Patients and methods - The Swedish Spine Register and the Swedish arthroplasty register were searched from 2000 through 2021. Chi-square, Kaplan-Meier and binary multivariate logistic regression were used to compare reop-eration rates up to 10 years after THA surgeryResults - 7,908 individuals had undergone lumbar spinal stenosis surgery (LSSS) (fusion n = 1,281) and THA. LSSS before THA compared with THA-only controls was associated with a higher risk of THA reoperations: 87 (2%) out of 3,892 vs. 123 (1%) out of 11,662 (P < 0.001). LSSS after THA compared with THA-only controls was not associ-ated with a higher risk of reoperation, confirmed by Kaplan- Meier analyses and binary multivariate logistic regression. Mortality was lower in individuals undergoing both LSSS and THA, regardless of procedure order. There was no dif-ference in THA reoperations in individuals who had under-gone LSSS before THA without fusion or with fusion. The individuals who had undergone LSSS after THA with fusion had an increased risk of THA reoperation compared with those without fusion.Conclusion - LSSS with or without fusion before THA is associated with an increased risk of THA reoperation. Spinal fusion increased the risk of reoperation of THA when performed after THA.
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| 49. |
- Englund, Emelie, et al.
(author)
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Cartilage oligomeric matrix protein promotes prostate cancer progression by enhancing invasion and disrupting intracellular calcium homeostasis
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:58, s. 98298-98311
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Journal article (peer-reviewed)abstract
- Cartilage oligomeric matrix protein (COMP) was recently implicated in the progression of breast cancer. Immunostaining of 342 prostate cancer specimens in tissue microarrays showed that COMP expression is not breast cancer-specific but also occurs in prostate cancer. The expression of COMP in prostate cancer cells correlated with a more aggressive disease with faster recurrence. Subcutaneous xenografts in immunodeficient mice showed that the prostate cancer cell line DU145 overexpressing COMP formed larger tumors in vivo as compared to mock-transfected cells. Purified COMP bound to and enhanced the invasion of DU145 cells in vitro in an integrin-dependent manner. In addition, intracellular COMP expression interfered with cellular metabolism by causing a decreased level of oxidative phosphorylation with a concurrent upregulation of lactate production (Warburg effect). Further, expression of COMP protected cells from induction of apoptosis via several pathways. The effect of COMP on metabolism and apoptosis induction was dependent on the ability of COMP to disrupt intracellular Ca2+ signalling by preventing Ca2+ release from the endoplasmic reticulum. In conclusion, COMP is a potent driver of the progression of prostate cancer, acting in an anti-apoptotic fashion by interfering with the Ca2+ homeostasis of cancer cells.
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| 50. |
- Engström, Emma, PhD, 1982-, et al.
(author)
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Comparing and modeling the use of online recommender systems
- 2024
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In: Computers in Human Behavior Reports. - : Elsevier BV. - 2451-9588. ; 15
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Journal article (peer-reviewed)abstract
- This study explores a new way to model the adoption of AI, specifically online recommender systems. It aims to find factors that can explain the variation in usage in terms of differences between individuals and differences over technologies. We analyzed survey data from users of online platforms in the U.S. using a two-level structural equation model (SEM) (N = 1007). In this model, the dependent variable was the usage rate, which was defined as the share of time a person used a particular recommender system (e.g., “People You May Know”) when they use the platform (e.g., Facebook). The individual responses (within-systems level) were clustered in the 26 recommender systems (between-systems level). We hypothesized that three technology-specific factors, adapted from the Diffusion of Innovations (DOI) theory and the Unified Theory of Acceptance and Use of Technology 2 (UTAUT2), could explain the variations in usage at both levels: perceived performance expectancy (PE), perceived effort expectancy (EE), and perceived hedonic motivation (HM). Our estimated model showed that usage was associated with PE and HM at the within-system level and only with PE at the between-system level. A considerable part of the variation in usage across the 26 systems could be explained by PE only (R2 = 0.30). The most important contribution to practitioners is that this study provides evidence for the idea that there are inherent, measurable differences across recommender technologies that affect their usage rates, and specifically it finds usefulness to be a key factor. This is potentially valuable for app developers and marketeers who look to promote the adoption of novel recommender systems. The main contribution to the literature is that it presents a proof-of-concept of a two-level model for AI adoption, conceptualizing it as an effect of both variations over users and variations over applications. This finding is potentially valuable for policymakers, as better predictive models might enable improved assessments of AI's social implications. In future studies, the two-level approach presented here could be applied to other forms of AI, such as voice assistants, chatbots, or Internet of Things (IoT).
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