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| 2. |
- Baptista, Marisa A. P., et al.
(author)
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Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Wiskott-Aldrich syndrome (WAS) is caused by loss-of-function mutations in the WASp gene. Decreased cellular responses in WASp-deficient cells have been interpreted to mean that WASp directly regulates these responses in WASp-sufficient cells. Here, we identify an exception to this concept and show that WASp-deficient dendritic cells have increased activation of Rac2 that support cross-presentation to CD8(+) T cells. Using two different skin pathology models, WASp-deficient mice show an accumulation of dendritic cells in the skin and increased expansion of IFN gamma-producing CD8(+) T cells in the draining lymph node and spleen. Specific deletion of WASp in dendritic cells leads to marked expansion of CD8(+) T cells at the expense of CD4(+) T cells. WASp-deficient dendritic cells induce increased cross-presentation to CD8(+) T cells by activating Rac2 that maintains a near neutral pH of phagosomes. Our data reveals an intricate balance between activation of WASp and Rac2 signalling pathways in dendritic cells.
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| 3. |
- Dahl, F, et al.
(author)
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Imaging single DNA molecules for high precision NIPT
- 2018
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
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Journal article (peer-reviewed)abstract
- Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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| 4. |
- Gerasimcik, Natalija, et al.
(author)
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The Rho GTPase Cdc42 Is Essential for the Activation and Function of Mature B Cells
- 2015
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 194:10, s. 4750-4758
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Journal article (peer-reviewed)abstract
- The Rho GTPase Cdc42 coordinates regulation of the actin and the microtubule cytoskeleton by binding and activating the Wiskott-Aldrich syndrome protein. We sought to define the role of intrinsic expression of Cdc42 by mature B cells in their activation and function. Mice with inducible deletion of Cdc42 in mature B cells formed smaller germinal centers and had a reduced Ab response, mostly of low affinity to T cell-dependent Ag, compared with wild-type (WT) controls. Spreading formation of long protrusions that contain F-actin, microtubules, and Cdc42-interacting protein 4, and assumption of a dendritic cell morphology in response to anti-CD40 plus IL-4 were impaired in Cdc42-deficient B cells compared with WT B cells. Cdc42-deficient B cells had an intact migratory response to chemokine in vitro, but their homing to the B cell follicles in the spleen in vivo was significantly impaired. Cdc42-deficient B cells induced a skewed cytokine response in CD4(+) T cells, compared with WT B cells. Our results demonstrate a critical role for Cdc42 in the motility of mature B cells, their cognate interaction with T cells, and their differentiation into Ab-producing cells.
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| 5. |
- Hameleers, M., et al.
(author)
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Start Spreading the News: A Comparative Experiment on the Effects of Populist Communication on Political Engagement in Sixteen European Countries
- 2018
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In: International Journal of Press-Politics. - : SAGE Publications. - 1940-1612 .- 1940-1620. ; 23:4, s. 517-538
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Journal article (peer-reviewed)abstract
- Although populist communication has become pervasive throughout Europe, many important questions on its political consequences remain unanswered. First, previous research has neglected the differential effects of populist communication on the Left and Right. Second, internationally comparative studies are missing. Finally, previous research mostly studied attitudinal outcomes, neglecting behavioral effects. To address these key issues, this paper draws on a unique, extensive, and comparative experiment in sixteen European countries (N = 15,412) to test the effects of populist communication on political engagement. The findings show that anti-elitist populism has the strongest mobilizing effects, and anti-immigrant messages have the strongest demobilizing effects. Moreover, national conditions such as the level of unemployment and the electoral success of the populist Left and Right condition the impact of populist communication. These findings provide important insights into the persuasiveness of populist messages spread throughout the European continent.
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| 6. |
- Haugdahl, H. S., et al.
(author)
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The breath of life. Patients' experiences of breathing during and after mechanical ventilation
- 2017
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In: Intensive and Critical Care Nursing. - : Elsevier BV. - 0964-3397. ; 40, s. 85-93
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Journal article (peer-reviewed)abstract
- Introduction: Breathlessness is a prevalent and distressing symptom in intensive care, underestimated by nurses and physicians. Therefore, to develop a more comprehensive understanding of this problem, the study had two aims: to compare patients' self-reported scores of breathlessness obtained during mechanical ventilation (MV) with experiences of breathlessness later recalled by patients and: to explore the lived experience of breathing during and after MV. Method: A qualitatively driven sequential mixed method design combining prospective observational breathlessness data at the end of a spontaneous breathing trial (SBT) and follow up data from 11 post discharge interviews. Findings: Four out of six patients who reported breathlessness at the end of an SBT did not remember being breathless in retrospect. Experiences of breathing intertwined with the whole illness experience and were described in four themes: existential threat; the tough time; an amorphous and boundless body and getting through. Conclusion: Breathing was not always a clearly separate experience, but intertwined with the whole illness experience. This may explain the poor correspondence between patients' and clinicians assessments of breathlessness. The results suggest patients' own reports of breathing should form part of nursing interventions and follow-up to support patients' quest for meaning. (C) 2017 Elsevier Ltd. All rights reserved.
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| 7. |
- Volpi, S, et al.
(author)
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N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome
- 2016
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 127:2, s. 216-220
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Journal article (peer-reviewed)abstract
- Mice lacking both WASP and N-WASP in B lymphocytes have impaired response to T-cell-dependent antigens and defective B-cell activation. Deletion of N-WASP in B cells attenuates autoimmunity in WASP-deficient mice.
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| 8. |
- Wiemerslage, Lyle, et al.
(author)
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A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels
- 2017
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 41:6, s. 990-994
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Journal article (peer-reviewed)abstract
- We investigated five methylation markers recently linked to body-mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus, and frontal gyri, some of which have been previously associated to food signaling, obesity, or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity, and genetic differences.
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| 9. |
- Abbott, Allan, 1978-, et al.
(author)
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Understanding the role of diabetes in the osteoarthritis disease and treatment process: a study protocol for the Swedish Osteoarthritis and Diabetes (SOAD) cohort
- 2019
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In: Bmj Open. - : BMJ. - 2044-6055. ; 9:12
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Journal article (peer-reviewed)abstract
- Introduction Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability worldwide. Metabolic comorbidities such as type II diabetes occur with a higher rate in people with OA than in the general population. Several factors including obesity, hyperglycaemia toxicity and physical inactivity have been suggested as potential links between diabetes and OA, and have been shown to negatively impact patients' health and quality of life. However, little is known on the role of diabetes in determining the outcome of non-surgical and surgical management of OA, and at the same time, how different OA interventions may affect diabetes control. Thus, the overall aim of this project is to explore (1) the impact of diabetes on the outcome of non-surgical and surgical OA treatments and (2) the impact of non-surgical and surgical OA treatments on diabetes control. Methods and analysis The study cohort is based on prospectively ascertained register data on a national level in Sweden. Data from OA patients who received a first-line non-surgical intervention and are registered in the National Quality Register for Better Management of Patients with Osteoarthritis will be merged with data from the Swedish Knee and Hip Arthroplasty Registers and the National Diabetes Register. Additional variables regarding patients' use of prescribed drugs, comorbidities, socioeconomic status and cause of death will be obtained through other national health and population data registers. The linkage will be performed on an individual level using unique personal identity numbers. Ethics and dissemination This study received ethical approval (2019-02570) from the Swedish Ethical Review Authority. Results from this cohort will be submitted to peer-reviewed scientific journals and reported at the leading national and international meetings in the field.
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| 10. |
- Arnesen, S., et al.
(author)
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Do Polls Influence Opinions? Investigating Poll Feedback Loops Using the Novel Dynamic Response Feedback Experimental Procedure
- 2018
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In: Social Science Computer Review. - : SAGE Publications. - 0894-4393 .- 1552-8286. ; 36:6, s. 735-743
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Journal article (peer-reviewed)abstract
- Opinion polls may inadvertently affect public opinion, as people may change their attitudes after learning what others think. A disconcerting possibility is that opinion polls have the ability to create information cascades, wherein the majority opinion becomes increasingly larger over time. Testing poll influence on attitudes toward Syrian refugees and mandatory measles vaccination, we field survey experiments on a probability-based online survey panel. Through a novel automated procedure labeled the dynamic response feedback, we measure whether the answers from early poll respondents can influence the opinions of subsequent respondents who learn the answers of the previous respondents. Using this procedure, no feedback loops are identified.
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