| 1. |
- Axelsson, Ulrik, et al.
(författare)
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Strukturerad miljödatahantering inom järn- och stålindustri. Etapp 2; Miljöinformationssystem
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det analysarbete som gjorts har i denna etapp har genomförts i samarbete med samma tre typföretag - Höganäs AB, Sandvik Materials Technology samt Ovako Steel AB - som i etapp 1. De tre företagen hanterar vardera en avsevärda mängd miljödata som idag finns utspridd inom organisationerna och lagras i olika system varför sammanställningar försvåras. Det betyder att den miljödata som mäts och beräknas lagras på ett sätt som innebär en irrationell hantering av den samlade miljöinformationen. Den analys som visar att det inom järn- och stålbranschen går att beskriva verksamhetsprocesser på ett enhetligt sätt och att miljödatan som företagen mäter, beräknar och lagrar överensstämmer i mycket stor grad. Baserat på detta har en branschgemensam miljödatastruktur varit möjlig att ta fram. Denna struktur är framtagen för att kunna lagra miljödata för utsläpp till luft, utsläpp till vatten, energianvändning och avfall. Utifrån den miljödatastruktur som arbetats fram och genom diskussioner med representanter för typföretagen i projektet har en översiktlig systemskiss för ett miljöinformationssystem inom järn- och stålindustrin tagits fram. Detta miljöinformationssystem kan vara generellt inom branschen och svara upp mot gemensamma krav på hantering av miljödata.
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| 2. |
- Bankvall, Maria, et al.
(författare)
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A family-based genome-wide association study of recurrent aphthous stomatitis
- 2020
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Ingår i: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 26:8, s. 1696-1705
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors. Oral Diseases published by John Wiley & Sons Ltd Objectives: The aetiology of recurrent aphthous stomatitis (RAS) remains unknown. Individuals may share features of genetic susceptibility, and there may also be a hereditary component. The aim was to identify patterns of association and segregation for genetic variants and to identify the genes and signalling pathways that determine the risk of developing RAS, through a family-based genome-wide association study (GWAS). Subjects and methods: DNA was extracted from buccal swabs of 91 individuals in 16 families and analysed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (dFAM) was used to derive SNP association values across all chromosomes. Results: None of the final 288,452 SNPs reached the genome-wide significant threshold of 5×10–8. The most significant pathways were the Ras and PI3K-Akt signalling pathways, pathways in cancer, circadian entrainment and the Rap 1 signalling pathway. Conclusions: This confirms that RAS is not monogenic but results as a consequence of interactions between multiple host genes and possibly also environmental factors. The present approach provides novel insights into the mechanisms underlying RAS and raises the possibility of identifying individuals at risk of acquiring this condition.
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| 3. |
- Bankvall, Maria, et al.
(författare)
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The engagement of oral-associated lymphoid tissues during oral versus gastric antigen administration
- 2016
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Ingår i: Immunology. - : Wiley. - 0019-2805. ; 149:1, s. 98-110
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Tidskriftsartikel (refereegranskat)abstract
- The role of oral-associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T-cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA-specific DO11.10+ CD4(+) T cells, stained with CellTrace Violet dye, through intravenous injection. Proliferating OVA-specific T cells were detected in the nose-associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time-points following OVA exposure. OVA-specific T-cell proliferation was initially observed in the NALT 1hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T-cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi-effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA-induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes.
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| 4. |
- Bankvall, Maria, et al.
(författare)
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The oral microbiota of patients with recurrent aphthous stomatitis.
- 2014
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Ingår i: Journal of oral microbiology. - : Informa UK Limited. - 2000-2297. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Specific pathogenic bacteria have been implicated in recurrent aphthous stomatitis (RAS), a chronic inflammatory condition characterised by ulcerations in the oral mucosa. However, the aetiology behind this condition still remains unclear.
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| 5. |
- Bankvall, Maria, et al.
(författare)
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Tissue-specific Differences in Immune Cell Subsets Located in the Naso-oropharyngeal-associated Lymphoid Tissues
- 2018
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475. ; 87:1, s. 15-27
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Tidskriftsartikel (refereegranskat)abstract
- Defining the immune cells within the naso-oropharyngeal-associated lymphoid tissues would promote the development of efficient orally and nasally delivered immunotherapies. The aim was to compare murine antigen-presenting cells (APCs) and T cell subsets in the nose-associated lymphoid tissues (NALT), cervical lymph nodes (CLN), mesenteric lymph nodes (MLN) and peripheral lymph nodes (PLN) using flow cytometry and in vitro proliferation assays. Overall, the NALT contained a higher proportion of APCs and a lower proportion of T cells compared to the CLN, MLN and PLN. The APCs of the NALT more often belonged to the CD11c(+)CD11b(+) and the CD11c(neg)CD11b(+) subsets as compared to the other sites. Both of these APC populations showed little sign of activation, that is low expression of the markers CD40, CD86 and IAd. Instead, the APCs of the NALT more often co-expressed CX3CR1 and CD206, markers associated with a tolerogenic function. No increase in the proportion of regulatory T cells was observed in the NALT. Instead, the T cells frequently exhibited a memory/effector phenotype, expressing the homing markers 47, CCR4 and CCR9, but rarely the naive phenotype cell surface marker CD45RB. In contrast, the T cells at the other sites were mostly of the naive phenotype. In addition, cells from the NALT did not proliferate upon in vitro stimulation with Con A, whereas the cells from the other sites did. Taken together, these results suggest that the NALT is primarily an effector site rather than one for activation and differentiation, despite it being regarded as a site of induction.
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| 6. |
- Berg, Elisabeth Gräslund, et al.
(författare)
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Praktiker som gör skillnad : Om den verb-inriktade metoden
- 2013
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Ingår i: Historisk Tidskrift. - 0345-469X .- 2002-4827. ; 133:3, s. 335-354
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Tidskriftsartikel (refereegranskat)abstract
- This article discusses the so-called verb-oriented method and its role in the research project Gender and Work in early modern Sweden (GaW), which is based at Uppsala University. It provides a presentation of the GaW-database, which has been designed to allow analysis according to the verb-method. Finally, the article points out that this method can be combined with a number of different theoretical approaches as long as the focus is on practices. It is therefore compatible with the approaches of e.g., Judith Butler, Michel de Certeau, and Amartya Sen. Work is defined as "time-use with the purpose of making a living" and the article discusses why data on time-use, or actual work activities, are better suited for research into early modern Swedish working life than other types of data. It shows that activities are usually described in the sources by verb-phrases, and explains how and from what sources verb-phrases are collected and analyzed within the project. In order to allow for generalizations the verb-method presupposes large amounts of data. This is the rationale for the GaW-database, which at present includes around 5000 verb-phrases and 75000 data posts.
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| 7. |
- Carlsson, Johan, 1987, et al.
(författare)
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The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro : AA and DHA Induce DCs That Suppress T Cells
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naive T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 muM fatty acids; alpha-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNgamma. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.
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| 8. |
- Carlsson, Johan, 1987, et al.
(författare)
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The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 10:11, s. e0143741-
-
Tidskriftsartikel (refereegranskat)abstract
- Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naive T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 muM fatty acids; alpha-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNgamma. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.
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| 9. |
- Chen, Tingsu, et al.
(författare)
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Identification of gliadin-binding peptides by phage display
- 2011
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Ingår i: BMC Biotechnology. - : Springer Science and Business Media LLC. - 1472-6750. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coeliac disease (CD) is a common and complex disorder of the small intestine caused by intolerance to wheat gluten and related edible cereals like barley and rye. Peptides originating from incomplete gliadin digestion activate the lamina propria infiltrating T cells to release proinflammatory cytokines, which in turn cause profound tissue remodelling of the small intestinal wall. There is no cure for CD except refraining from consuming gluten-containing products. RESULTS: Phage from a random oligomer display library were enriched by repeated pannings against immobilised gliadin proteins. Phage from the final panning round were plated, individual plaques picked, incubated with host bacteria, amplified to a population size of 1011 to 1012 and purified. DNA was isolated from 1000 purified phage populations and the region covering the 36 bp oligonucleotide insert from which the displayed peptides were translated, was sequenced. Altogether more than 150 different peptide-encoding sequences were identified, many of which were repeatedly isolated under various experimental conditions. Amplified phage populations, each expressing a single peptide, were tested first in pools and then one by one for their ability to inhibit binding of human anti-gliadin antibodies in ELISA assays. These experiments showed that several of the different peptide-expressing phage tested inhibited the interaction between gliadin and anti-gliadin antibodies. Finally, four different peptide-encoding sequences were selected for further analysis, and the corresponding 12-mer peptides were synthesised in vitro. By ELISA assays it was demonstrated that several of the peptides inhibited the interaction between gliadin molecules and serum anti-gliadin antibodies. Moreover, ELISA competition experiments as well as dot-blot and western blot revealed that the different peptides interacted with different molecular sites of gliadin. CONCLUSIONS: We believe that several of the isolated and characterised gliadin-binding peptides described here could provide valuable tools for researchers in the field of CD by facilitating studies on localisation and uptake of various gliadin peptides in the small intestine. In future work, the potential of these peptides to detoxify gluten will be investigated.
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| 10. |
- Corvigno, Sara, et al.
(författare)
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High density of stroma-localized CD11c-positive macrophages is associated with longer overall survival in high-grade serous ovarian cancer.
- 2020
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 159:3, s. 860-868
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Pre-clinical studies have identified marker- and tumor compartment-defined functionally distinct macrophage subsets. Our study analyzes marker-defined macrophage subsets in different tumor compartments of high-grade serous ovarian cancer (HGSC).METHODS: A discovery cohort (N = 113) was subjected to immunohistochemistry (IHC) analyses. CD68-positivity was confirmed for CD11c-, CD80- and CD163-positive cells. Subset-marker-positive cells were scored in the total tumor and in four tumor compartments. Correlation analyses investigated co-expression of subsets, relationship to CD8+ cells and survival associations. A validation cohort (N = 121) was used to confirm selected findings from the discovery cohort.RESULTS: CD163-positve cells was the most abundant subtype in all compartments. CD11c and CD163 subsets were strongly correlated with each other in stroma and epithelial areas, whereas CD80 and CD163 were correlated in epithelial areas. CD80 and CD11c in perivascular areas showed low correlations. Strong associations were detected between CD8 and CD80 in the tumor epithelium-dominated areas, and between CD8 and CD11c in stroma areas. High stromal CD11c density was associated with a longer median overall survival in the discovery cohort (HR 0.39; CI 95%, 0.23-0.68; p = 0.001) and in the validation cohort (HR 0.46; CI 95%, 0.22-0.93; p = 0.03).CONCLUSIONS: Our study supports the existence of clinically relevant marker- and localization defined macrophage subsets in HGSC, which are independently regulated. Moreover, it suggests stromal CD11c as a novel prognostic marker in HGSC.
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| 11. |
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| 12. |
- Gale, Gita, et al.
(författare)
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Does Crohn's Disease with Concomitant Orofacial Granulomatosis Represent a Distinctive Disease Subtype?
- 2016
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 22:5, s. 1071-1077
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although orofacial granulomatosis (OFG) may present as a separate clinical entity, it often seems in conjunction with various systemic diseases, of which Crohn's disease (CD) is one of the most common. The aim of this study was to investigate whether CD with concomitant OFG represents a distinctive disease subtype. Methods: Twenty-one patients with CD and concomitant OFG (CD+OFG group) were included in the study. As the reference group, a cohort of 39 patients with CD but without OFG (CD-R group) was used. Demographic data and clinical characteristics were recorded at the time of diagnosis. The 2 groups were compared using multivariate analyses. Results: The percentage of patients with intestinal inflammation in the upper gastrointestinal tract was significantly higher in the CD+OFG group, as compared with the CD-R group (81% versus 33%; P < 0.001). Furthermore, ileocolonic inflammation was significantly more common in the CD+OFG patients (81% versus 46%; P = 0.013). In addition, perianal disease was more frequently observed in the CD+OFG group (48% versus 18%; P = 0.033). Significantly more patients showed evidence of granulomas in the primary endoscopy in the CD+OFG group than in the CD-R group (81% versus 38%; P = 0.003). Conclusion: The data from this study suggest that the presence of CD in conjunction with OFG represents a distinctive subphenotype of CD that is characterized by extensive inflammation, perianal disease, and pronounced granuloma formation in the intestine.
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| 13. |
- Gale, Gita, et al.
(författare)
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Immunophenotype in orofacial granulomatosis with and without Crohn's disease.
- 2014
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Ingår i: Medicina oral, patología oral y cirugía bucal. - : Medicina Oral, S.L.. - 1698-6946. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this investigation was to characterise and compare the inflammatory infiltrates in patients with orofacial granulomatosis solely (OFG-S) and OFG with coexisting Crohn's disease (OFG+CD).
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| 14. |
- Gale, Gita, et al.
(författare)
-
Reply.
- 2016
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Ingår i: Inflammatory bowel diseases. - 1536-4844. ; 22:7
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Groundstroem, Henrik, et al.
(författare)
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A systematic mapping of Nordic youth surveys
- 2020
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Konferensbidrag (refereegranskat)abstract
- Aim: The aim of this study was to map the existing Nordic youth surveys and to answer the following research questions: how many youth surveys are conducted in the Nordic countries?, what major youth surveys are being conducted in all Nordic countries?, and what themes do the existing questionnaires deal with in the various countries?Method: Data was collected from January to April 2018 through a systematic mapping technique and the surveys were analyzed according to quality criteria.Results: The results showed a total of 143 surveys and after exclusion due to poor survey quality, 82 fit the inclusion criteria. In the Nordic countries, six surveys were identified that covered all Nordic countries. The themes that youth surveys usually focus on are criminality, school, physical and mental health, addiction, societal participation and family relationships.Conclusion: Many similar youth surveys exist both nationally and on a Nordic level. During the last forty years, there has also been an exponential increase in surveys aimed at young people. A larger coordination of these surveys would be beneficial and increase their quality as well as limit the number of surveys that young people are exposed to. This study identifies the need for a coordinated Nordic youth survey and the potential benefits on a regional, national and Nordic level.
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| 16. |
- Hultkrantz, Susanne, 1977, et al.
(författare)
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Induction of antigen-specific regulatory T cells in the liver-draining celiac lymph node following oral antigen administration.
- 2005
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 116:3, s. 362-72
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells are induced by oral administration of an antigen, but the physiological requirements and localization of the inductive sites are largely unknown. Using an adoptive transfer system of cells transgenic for ovalbumin T-cell receptor (OVA TCR tg), we found that antigen-specific CD4+ T cells were activated in the liver-draining celiac lymph node (CLN) shortly after ovalbumin feeding, and that a significantly higher proportion of the T cells in the CLN developed into the putative regulatory phenotype [co-expressing CD25 with the glucocortico-induced tumour necrosis factor (TNF) receptor family related gene (GITR), cytotoxic T-lymphocyte antigen (CTLA)-4 and CD103] than in Peyer's patches, the mesenteric and peripheral lymph nodes and the spleen. In addition, a particularly high level of expression of CD103 on the OVA-specific T cells in the CLN may favour homing to the epithelium of the intestine. While equally suppressive, OVA tg T cells isolated from the CLN of OVA-fed DO11.10 mice were less dependent on transforming growth factor (TGF)-beta for suppression than cells isolated from the peripheral and mesenteric lymph nodes, which indicates the involvement of an additional suppressive mechanism. The expression of FoxP3 was not up-regulated in any of the lymph node compartments studied. Our phenotypic and functional findings suggest that the induction of regulatory T cells in the CLN may be relevant in the control of the immune response to dietary antigens.
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| 17. |
- Johansson, Sara, 1977, et al.
(författare)
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Long-chain polyunsaturated fatty acids are consumed during allergic inflammation and affect T helper type 1 (Th1)- and Th2-mediated hypersensitivity differently
- 2010
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 160:3, s. 411-419
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Tidskriftsartikel (refereegranskat)abstract
- P>Studies have shown that atopic individuals have decreased serum levels of n-3 fatty acids. Indicating these compounds may have a protective effect against allergic reaction and/or are consumed during inflammation. This study investigated whether fish (n-3) or sunflower (n-6) oil supplementation affected T helper type 1 (Th1)- and Th2-mediated hypersensitivity in the skin and airways, respectively, and whether the fatty acid serum profile changed during the inflammatory response. Mice were fed regular chow, chow + 10% fish oil or chow + 10% sunflower oil. Mice were immunized with ovalbumin (OVA) resolved in Th1 or Th2 adjuvant. For Th1 hypersensitivity, mice were challenged with OVA in the footpad. Footpad swelling, OVA-induced lymphocyte proliferation and cytokine production in the draining lymph node were evaluated. In the airway hypersensitivity model (Th2), mice were challenged intranasally with OVA and the resulting serum immunoglobulin (Ig)E and eosinophilic lung infiltration were measured. In the Th1 model, OVA-specific T cells proliferated less and produced less interferon (IFN)-gamma, tumour necrosis factor (TNF) and interleukin (IL)-6 in fish oil-fed mice versus controls. Footpad swelling was reduced marginally. In contrast, mice fed fish oil in the Th2 model produced more OVA-specific IgE and had slightly higher proportions of eosinophils in lung infiltrate. A significant fall in serum levels of long-chain n-3 fatty acids accompanied challenge and Th2-mediated inflammation in Th2 model. Fish oil supplementation affects Th1 and Th2 immune responses conversely; significant consumption of n-3 fatty acids occurs during Th2-driven inflammation. The latter observation may explain the association between Th2-mediated inflammation and low serum levels of n-3 fatty acids.
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| 18. |
- Larkin, Cormac J.K., et al.
(författare)
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M5 — Mars Magnetospheric Multipoint Measurement Mission: A multi-spacecraft plasma physics mission to Mars
- 2024
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Ingår i: Advances in Space Research. - : Elsevier. - 0273-1177 .- 1879-1948. ; 73:6, s. 3235-3255
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Tidskriftsartikel (refereegranskat)abstract
- Mars, lacking an intrinsic dynamo, is an ideal laboratory to comparatively study induced magnetospheres, which can be found in other terrestrial bodies as well as comets. Additionally, Mars is of particular interest to further exploration due to its loss of habitability by atmospheric escape and possible future human exploration. In this context, we propose the Mars Magnetospheric Multipoint Measurement Mission (M5), a multi-spacecraft mission to study the dynamics and energy transport of the Martian induced magnetosphere comprehensively. Particular focus is dedicated to the largely unexplored magnetotail region, where signatures of magnetic reconnection have been found. Furthermore, a reliable knowledge of the upstream solar wind conditions is needed to study the dynamics of the Martian magnetosphere, especially the different dayside boundary regions but also for energy transport phenomena like the current system and plasma waves. This will aid the study of atmospheric escape processes of planets with induced magnetospheres. In order to resolve the three-dimensional structures varying both in time and space, multi-point measurements are required. Thus, M5 is a five spacecraft mission, with one solar wind monitor orbiting Mars in a circular orbit at 5 Martian radii, and four smaller spacecraft in a tetrahedral configuration orbiting Mars in an elliptical orbit, spanning the far magnetotail up to 6 Mars radii with a periapsis just outside the Martian magnetosphere of 1.8 Mars radii. We not only present a detailed assessment of the scientific need for such a mission but also show the resulting mission and spacecraft design taking into account all aspects of the mission requirements and constraints such as mass, power, and link budgets. Additionally, different aspects of the mission programmatics like a possible mission timeline, cost estimates, or public outreach are shown. The common requirements for acceptance for an ESA mission are considered. The mission outlined in this paper was developed during the Alpbach Summer School 2022 on the topic of “Comparative Plasma Physics in the Universe”.
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| 19. |
- Lönnqvist, Anna, 1980, et al.
(författare)
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Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy.
- 2009
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Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 39:2, s. 447-56
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Tidskriftsartikel (refereegranskat)abstract
- The hygiene hypothesis suggests that lack of microbial stimulation in early infancy may lead to allergy, but it has been difficult to identify particular protective microbial exposures. We have observed that infants colonised in the first week(s) of life with Staphylococcus aureus have lower risk of developing food allergy. As many S. aureus strains produce superantigens with T-cell stimulating properties, we here investigate whether neonatal mucosal exposure to superantigen could influence the capacity to develop oral tolerance and reduce sensitisation and allergy. BALB/c mice were exposed to staphylococcal enterotoxin A (SEA) as neonates and fed with OVA as adults, prior to sensitisation and i.n. OVA challenge. Our results show that SEA pre-treated mice are more efficiently tolerised by OVA feeding, as shown by lower lung-cell infiltration and antigen-specific IgE response in the SEA pre-treated mice, compared with sham-treated mice. This was not due to deletion or anergy of lymphocytes by SEA treatment, because the SEA pre-treated mice that were fed with PBS showed similar inflammatory response as the sham-treated PBS-fed mice. Our results suggest that strong T-cell activation in infancy conditions the mucosal immune system and promotes development of oral tolerance.
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| 20. |
- Marco, Maugeri, 1983, et al.
(författare)
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Linkage between endosomal escape of LNP-mRNA and loading into EVs for transport to other cells
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- RNA-based therapeutics hold great promise for treating diseases and lipid nanoparticles (LNPs) represent the most advanced platform for RNA delivery. However, the fate of the LNP-mRNA after endosome-engulfing and escape from the autophagy-lysosomal pathway remains unclear. To investigate this, mRNA (encoding human erythropoietin) was delivered to cells using LNPs, which shows, for the first time, a link between LNP-mRNA endocytosis and its packaging into extracellular vesicles (endo-EVs: secreted after the endocytosis of LNP-mRNA). Endosomal escape of LNP-mRNA is dependent on the molar ratios between ionizable lipids and mRNA nucleotides. Our results show that fractions of ionizable lipids and mRNA (1:1 molar ratio of hEPO mRNA nucleotides:ionizable lipids) of endocytosed LNPs were detected in endo-EVs. Importantly, these EVs can protect the exogenous mRNA during in vivo delivery to produce human protein in mice, detected in plasma and organs. Compared to LNPs, endo-EVs cause lower expression of inflammatory cytokines.
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| 21. |
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| 22. |
- Rabe, Hardis, et al.
(författare)
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Distinct patterns of naive, activated and memory T and B cells in blood of patients with ulcerative colitis or Crohn’s disease
- 2019
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 197:1, s. 111-129
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Tidskriftsartikel (refereegranskat)abstract
- Both major subcategories of inflammatory bowel disease (IBD), ulcerative colitis and Crohn’s disease are characterized by infiltration of the gut wall by inflammatory effector cells and elevated biomarkers of inflammation in blood and feces. We investigated the phenotypes of circulating lymphocytes in the two types of IBD in treatment-naive pediatric patients by analysis of blood samples by flow cytometry. Multivariate analysis was used to compare the phenotypes of the blood lymphocytes of children with ulcerative colitis (n=17) or Crohn’s disease (n=8) and non-IBD control children with gastrointestinal symptoms, but no signs of gut inflammation (n=23). The two IBD subcategories could be distinguished based on the results from the flow cytometry panel. Ulcerative colitis was characterized by activated T cells, primarily in the CD8+ population, as judged by increased expression of human leukocyte antigen D-related (HLA-DR) and the β1-integrins [very late antigen (VLA)] and a reduced proportion of naive (CD62L+) T cells, compared with the non-IBD controls. This T cell activation correlated positively with fecal and blood biomarkers of inflammation. In contrast, the patients with Crohn’s disease were characterized by a reduced proportion of B cells of the memory CD27+ phenotype compared to the non-IBD controls. Both the patients with ulcerative colitis and those with Crohn’s disease showed increased percentages of CD23+ B cells, which we demonstrate here as being naive B cells. The results support the notion that the two major forms of IBD may partially have different pathogenic mechanisms.
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| 23. |
- Sjöberg, Fei, et al.
(författare)
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Low-complexity microbiota in the duodenum of children with newly diagnosed ulcerative colitis
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- Background Inflammatory bowel disease (IBD) is characterized by gut dysbiosis. To date, the large bowel microbiota has been in focus. However, the microbiota of the small intestine may also be of importance, as the small bowel is a site for the induction and control of mucosal immune responses, which can be modulated by constituents of the local microbiota. Duodenal fluids were collected during diagnostic work-up of treatment-naive children who were suspected of having IBD. The duodenal fluids were analyzed by pyrosequencing (average of 32,000 reads/sample, read length of 500 nucleotides). After diagnosis, the duodenal microbiota of subjects with ulcerative colitis (N = 8) or Crohn's disease (N = 5), and non-IBD controls (N = 8) were compared. Pyrosequencing revealed that the duodenal microbiota of children with ulcerative colitis contained fewer Operational Taxonomic Units (OTUs) per individual than the duodenal microbiota of the controls (P = 0.005). This reduction in richness of the duodenal microbiota was seen for three major phyla: Firmicutes, Actinobacteria, and Bacteroidetes. Several bacterial genera were detected less frequently in the children with ulcerative colitis than in the non-IBD controls, including Collinsella (P = 0.001), Lactobacillus (P = 0.007), and Bacillus (P = 0.007), as well as a non-identified member of the order Sphingobacteriales (P = 0.007). In this pilot study, we show that the duodenal microbiota of children with ulcerative colitis exhibits reduced overall richness, despite the fact that the inflammation is primarily localized to the colon. These results should be corroborated in a larger study.
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| 24. |
- Stern, Anna, 1980, et al.
(författare)
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Neonatal Mucosal Immune Stimulation by Microbial Superantigen Improves the Tolerogenic Capacity of CD103(+) Dendritic Cells
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Food allergy represents failure to develop tolerance to dietary proteins. Food allergy has increased in prevalence in parallel with decreased exposure to microbes during infancy. In mice, neonatal peroral exposure to the strongly T cell stimulating superantigen staphylococcal enterotoxin A (SEA), enhances the capacity to develop oral tolerance to a novel antigen encountered in adult life. A population of antigen-presenting cells in the gut, the CD103(+) dendritic cells (DCs), is thought to be involved in oral tolerance development, as they convert naive T cells into FoxP3(+) regulatory T cells (Treg). This function depends on their capacity to convert vitamin A to retinoic acid, carried out by the retinal aldehyde dehydrogenase (RALDH) enzyme. Here, newborn mice were treated with superantigen and DC function and tolerogenic capacity was examined at six weeks of age. We observed that, in mice fed superantigen neonatally, the CD11c(+) DCs had increased expression of RALDH and in vitro more efficiently induced expression Foxp3 expression to stimulated T cells. Further, these mice showed an accumulation of FoxP3(+) T cells in the small intestinal lamina propria and had a more Ag-specific FoxP3(+) T cells after oral tolerance induction in vivo. Moreover, the improved oral tolerance, as shown by increased protection from food allergy, was eradicated if the Vitamin A metabolism was inhibited. These observations contribute to the understanding of how a strong immune stimulation during the neonatal period influences the maturation of the immune system and suggests that such stimulation may reduce the risk of later allergy development.
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| 25. |
- Sundler, Annelie Johansson, 1973-, et al.
(författare)
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The patient’s first point of contact (PINPOINT) – protocol of a prospective multicenter study of communication and decision-making during patient assessments by primary care registered nurses
- 2023
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Ingår i: BMC Primary Care. - : BioMed Central Ltd. - 2731-4553. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: A major challenge for primary care is to set priorities and balance demands with available resources. The registered nurses in this study are practice nurses working in primary care offices, playing a large role in initial assessments. The overall objective of this research is to investigate practices of communication and decision-making during nurses’ initial assessment of patients’ health problems in primary care, examine working mechanisms in good practices and develop feasible solutions. Methods: Project PINPOINT aims for a prospective multicenter study using various methods for data collection and analysis. A purposive sample of 150 patient‒nurse consultations, including 30 nurses and 150 patients, will be recruited at primary care centers in three different geographic areas of southwest Sweden. The study will report on outcomes of communication practices in relation to patient-reported expectations and experiences, communication processes and patient involvement, assessment and decision-making, related priorities and value conflicts with data from patient questionnaires, audio-recorded real-time communication, and reflective interviews with nurses. Discussion: This research will contribute to the knowledge needed for the guidance of first-line decision-making processes to best meet patient and public health needs. This knowledge is necessary for the development of assessments and decisions to be better aligned to patients and to set priorities. Insights from this research can empower patients and service providers and help understand and enhance feasible person-centered communication strategies tailored to patients’ level of health literacy. More specifically, this research will contribute to knowledge that can strengthen nurses’ communication, assessments, and clinical decision-making in primary care. In the long term, this will contribute to how the competencies of practice nurses and other professionals are organized and carried out to make the best use of the resources within primary care. Trial registration: ClinicalTrials.gov Identifier: NCT06067672.
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