| 1. |
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| 2. |
- Li, Shunyi, et al.
(författare)
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Intrinsic energy band alignment of functional oxides
- 2014
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Ingår i: Physica Status Solidi - Rapid Research Letetrs. - : Wiley. - 1862-6254 .- 1862-6270. ; 8:6, s. 571-576
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Tidskriftsartikel (refereegranskat)abstract
- The energy band alignment at interfaces between different materials is a key factor, which determines the function of electronic devices. While the energy band alignment of conventional semiconductors is quite well understood, systematic experimental studies on oxides are still missing. This work presents an extensive study on the intrinsic energy band alignment of a wide range of functional oxides using photoelectron spectroscopy with in-situ sample preparation. The studied materials have particular technological importance in diverse fields as solar cells, piezotronics, multiferroics, photoelectrochemistry and oxide electronics. Particular efforts have been made to verify the validity of transitivity, in order to confirm the intrinsic nature of the obtained band alignment and to understand the underlying principles. Valence band offsets up to 1.6 eV are observed. The large variation of valence band maximum energy can be explained by the different orbital contributions to the density of states in the valence band. The framework provided by this work enables the general understanding and prediction of energy band alignment at oxide interfaces, and furthermore the tailoring of energy level matching for charge transfer in functional oxides. (C) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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| 3. |
- Sultana, M. Afifa, et al.
(författare)
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Downmodulation of Effector Functions in NK Cells upon Toxoplasma gondii Infection
- 2017
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 85:10
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Tidskriftsartikel (refereegranskat)abstract
- The obligate intracellular parasite Toxoplasma gondii can actively infect any nucleated cell type, including cells from the immune system. The rapid transfer of T. gondii from infected dendritic cells to effector natural killer (NK) cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection. However, subversion of NK cell functions, such as cytotoxicity or production of proinflammatory cytokines, such as gamma interferon (IFN-γ), upon parasite infection might also be beneficial to the parasite. In the present study, we investigated the effects of T. gondii infection on NK cells. In vitro, infected NK cells were found to be poor at killing target cells and had reduced levels of IFN-γ production. This could be attributed in part to the inability of infected cells to form conjugates with their target cells. However, even upon NK1.1 cross-linking of NK cells, the infected NK cells also exhibited poor degranulation and IFN-γ production. Similarly, NK cells infected in vivo were also poor at killing target cells and producing IFN-γ. Increased levels of transforming growth factor β production, as well as increased levels of expression of SHP-1 in the cytosol of infected NK cells upon infection, were observed in infected NK cells. However, the phosphorylation of STAT4 was not altered in infected NK cells, suggesting that transcriptional regulation mediates the reduced IFN-γ production, which was confirmed by quantitative PCR. These data suggest that infection of NK cells by T. gondii impairs NK cell recognition of target cells and cytokine release, two mechanisms that independently could enhance T. gondii survival.
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| 6. |
- Malzbender, K., et al.
(författare)
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Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer’s Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project
- 2024
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Ingår i: Journal of Prevention of Alzheimer's Disease. - 2274-5807 .- 2426-0266. ; 11:2, s. 329-338
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Tidskriftsartikel (refereegranskat)abstract
- The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer’s disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs.
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| 7. |
- Vanfleteren, Lowie E G W, et al.
(författare)
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Biomarker-based clustering of patients with chronic obstructive pulmonary disease
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Rationale COPD has been associated repeatedly with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways. This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterisation and examine how these differences may relate to altered biological pathways. Methods 213 patients with moderate-to-severe COPD in a clinically stable state were recruited and clinically characterised, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster. Results Four clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV), with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that three of the four clusters were enriched in Rage (receptor for advanced glycation end-products) and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterisation of clusters ranged from 1) better functional capacity and health status and fewer comorbidities; 2) more underweight, osteoporosis and static hyperinflation; 3) more metabolically deranged; and 4) older subjects with worse functional capacity and higher comorbidity load. Conclusions These new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.
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| 8. |
- Yang, Liyun, 1992-, et al.
(författare)
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Impact of Procedure Type, Case Duration, and Adjunctive Equipment on Surgeon Intraoperative Musculoskeletal Discomfort
- 2020
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Ingår i: Journal of the American College of Surgeons. - : ELSEVIER SCIENCE INC. - 1072-7515 .- 1879-1190. ; 230:4, s. 554-560
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Surgeons are at high risk of developing musculoskeletal disorders. STUDY DESIGN: This study was designed to identify risk factors and assess intraoperative physical stressors using subjective and objective measures, including type of procedure and equipment used. Wearable sensors and pre- and postoperation surveys were analyzed. RESULTS: Data from 116 cases (34 male and 19 female surgeons) were collected across surgical specialties. Surgeons reported increased pain in the neck, upper, and lower back both during and after operations. High-stress intraoperative postures were also revealed by the real-time measurement in the neck and back. Surgical duration also impacted physical pain and fatigue. Open procedures had more stressful physical postures than laparoscopic procedures. Loupe usage negatively impacted neck postures. CONCLUSIONS: This study highlights the fact that musculoskeletal disorders are common in surgeons and characterizes surgeons' intraoperative posture as well as surgeon pain and fatigue across specialties. Defining intraoperative ((C) 2020 The Author(s). Published by Elsevier Inc. on behalf of the American College of Surgeons.
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| 9. |
- Fuks, Jonas M, et al.
(författare)
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GABAergic Signaling Is Linked to a Hypermigratory Phenotype in Dendritic Cells Infected by Toxoplasma gondii
- 2012
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 8:12, s. e1003051-
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Tidskriftsartikel (refereegranskat)abstract
- During acute infection in human and animal hosts, the obligate intracellular protozoan Toxoplasma gondii infects a variety of cell types, including leukocytes. Poised to respond to invading pathogens, dendritic cells (DC) may also be exploited by T. gondii for spread in the infected host. Here, we report that human and mouse myeloid DC possess functional γ-aminobutyric acid (GABA) receptors and the machinery for GABA biosynthesis and secretion. Shortly after T. gondii infection (genotypes I, II and III), DC responded with enhanced GABA secretion in vitro. We demonstrate that GABA activates GABA(A) receptor-mediated currents in T. gondii-infected DC, which exhibit a hypermigratory phenotype. Inhibition of GABA synthesis, transportation or GABA(A) receptor blockade in T. gondii-infected DC resulted in impaired transmigration capacity, motility and chemotactic response to CCL19 in vitro. Moreover, exogenous GABA or supernatant from infected DC restored the migration of infected DC in vitro. In a mouse model of toxoplasmosis, adoptive transfer of infected DC pre-treated with GABAergic inhibitors reduced parasite dissemination and parasite loads in target organs, e.g. the central nervous system. Altogether, we provide evidence that GABAergic signaling modulates the migratory properties of DC and that T. gondii likely makes use of this pathway for dissemination. The findings unveil that GABA, the principal inhibitory neurotransmitter in the brain, has activation functions in the immune system that may be hijacked by intracellular pathogens.
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| 10. |
- Hilliges, M, et al.
(författare)
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ATP responses in human C nociceptors
- 2002
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959. ; 98:1-2, s. 59-68
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Tidskriftsartikel (refereegranskat)
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Tuncel, J., et al.
(författare)
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Animal Models of Rheumatoid Arthritis (I) : Pristane-Induced Arthritis in the Rat
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a series of protocols for different animal models of arthritis that reflect the pathogenesis of RA. Here, we describe chronic pristane-induced arthritis (PIA) model in DA rats, and provide detailed instructions to set up and evaluate the model and for reporting data. METHODS: We optimized dose of pristane and immunization procedures and determined the effect of age, gender, and housing conditions. We further assessed cage-effects, reproducibility, and frequency of chronic arthritis, disease markers, and efficacy of standard and novel therapies. RESULTS: Out of 271 rats, 99.6% developed arthritis after pristane-administration. Mean values for day of onset, day of maximum arthritis severity and maximum clinical scores were 11.8+/-2.0 days, 20.3+/-5.1 days and 34.2+/-11 points on a 60-point scale, respectively. The mean frequency of chronic arthritis was 86% but approached 100% in long-term experiments over 110 days. Pristane was arthritogenic even at 5 microliters dose but needed to be administrated intradermally to induce robust disease with minimal variation. The development of arthritis was age-dependent but independent of gender and whether the rats were housed in conventional or barrier facilities. PIA correlated well with weight loss and acute phase reactants, and was ameliorated by etanercept, dexamethasone, cyclosporine A and fingolimod treatment. CONCLUSIONS: PIA has high incidence and excellent reproducibility. The chronic relapsing-remitting disease and limited systemic manifestations make it more suitable than adjuvant arthritis for long-term studies of joint-inflammation and screening and validation of new therapeutics.
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| 16. |
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| 17. |
- Weidner, G, et al.
(författare)
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Cardiovascular reactivity to mental stress in the Stockholm Female Coronary Risk Study
- 2001
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Ingår i: Psychosomatic Medicine. - SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. Univ Educ, Dept Hlth Psychol, Schwabisch Gmund, Germany. Karolinska Inst, Dept Prevent Med, Stockholm, Sweden. Karolinska Inst, Dept Cardiol, Stockholm, Sweden. Karolinska Hosp, S-10401 Stockholm, Sweden. Univ Stockholm, Student Hlth Ctr, Stockholm, Sweden. : LIPPINCOTT WILLIAMS & WILKINS. - 0033-3174 .- 1534-7796. ; 63:6, s. 917-924
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study evaluated the ability of mental stress testing to discriminate between women with and without CHD, and among women with different disease manifestations, taking into account history of hypertension and beta -blocker use. Methods: Analyses were based on data from a community-based case-control study of women aged 65 years or younger. The study group consisted of 292 women who were hospitalized for an acute event of CHD, either AMI or unstable AP in Stockholm between 1991 and 1994. Controls were matched to cases by age and catchment area. Cardiovascular reactivity and emotional response to an anagram task solved under time pressure were measured 3 to 6 months after hospitalization. Results: Patients reacted with smaller increases in heart rate (4 bpm) than their controls (7 bpm). Results for the rate-pressure product were similar. Cardiovascular reactions did not distinguish patients with AP from those with AML History of hypertension (present in 50% of patients and 11% of controls) was related to enhanced diastolic blood pressure reactivity. Patients on beta -blockers (66%) had lower heart-rate levels throughout testing, but did not differ in their cardiovascular stress reactions when compared with the remaining participants. Conclusions: Women with heart disease have somewhat lower heart-rate responses to stress than healthy age-matched controls. History of hypertension is related to enhanced diastolic blood pressure reactivity to mental stress in both patients and controls.
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| 18. |
- Weidner, Jessica M., et al.
(författare)
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Rapid cytoskeleton remodelling in dendritic cells following invasion by Toxoplasma gondii coincides with the onset of a hypermigratory phenotype
- 2013
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 15:10, s. 1735-1752
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Tidskriftsartikel (refereegranskat)abstract
- Host cell manipulation is an important feature of the obligate intracellular parasite Toxoplasma gondii. Recent reports have shown that the tachyzoite stages subvert dendritic cells (DC) as a conduit for dissemination (Trojan horse) during acute infection. To examine the cellular basis of these processes, we performed a detailed analysis of the early events following tachyzoite invasion of human monocyte-derived DC. We demonstrate that within minutes after tachyzoite penetration, profound morphological changes take place in DC that coincide with a migratory activation. Active parasite invasion of DC led to cytoskeletal actin redistribution with loss of adhesive podosome structures and redistribution of integrins (CD18 and CD11c), that concurred with the onset of DC hypermotility in vitro. Inhibition of parasite rhoptry secretion and invasion, but not inhibition of parasite or host cell protein synthesis, abrogated the onset of morphological changes and hypermotility in DC dose-dependently. Also, infected DC, but not by-stander DC, exhibited upregulation of C-C chemokine receptor 7 (CCR7). Yet, the onset of parasite-induced DC hypermotility preceded chemotactic migratory responsesin vitro. Collectively, present data reveal that invasion of DC by T. gondii initiates a series of regulated events, including rapid cytoskeleton rearrangements, hypermotility and chemotaxis, that promote the migratory activation of DC.
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| 19. |
- Yang, Liyun, 1992-, et al.
(författare)
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Intraoperative musculoskeletal discomfort and risk for surgeons during open and laparoscopic surgery.
- 2020
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Ingår i: Surgical Endoscopy. - : Springer Nature. - 0930-2794 .- 1432-2218.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Surgeon workload is significant both mentally and physically and may differ by procedure type. When comparing laparoscopic surgery and open surgery, studies have reported contrasting results on the physical and mental workload assessed.METHODS: Wearable posture sensors and pre-/post-surgical questionnaires were employed to assess intraoperative workload and to identify risk factors for surgeons using objective and subjective measures.RESULTS: Data from 49 cases (27 open and 22 laparoscopic surgeries performed by 13 male and 11 female surgeons) were assessed. More than half the surgeons reported a clinically relevant post-surgical fatigue score. The surgeons also self-reported a significant increase in pain for the neck, upper back, and lower back during/after surgery. Procedural time had significant impacts on fatigue, body part pain, and subjective (NASA-TLX) workload. The objectively assessed intraoperative work postures using wearable sensors showed a high musculoskeletal risk for neck and lower back based on their posture overall. Open surgeries had significantly larger neck angles (median [IQR]: 40 [28-47]°) compared with laparoscopic surgeries (median [IQR]: 23 [16-29]°), p < 0.001) and torso (median [IQR]: 17 [14-22]° vs. 13 [10-17]°, p = 0.006).CONCLUSION: Surgeons reported significantly higher levels of fatigue and pain in the neck and lower back during or after performing a surgical case. Longer procedural time resulted in more self-rated fatigue, pain, and subjective workload. Open surgery had higher postural risk. Overall, surgeons spent a disturbingly high percentage of time during surgery in high-risk musculoskeletal postures, especially the neck. These results show that intraoperative postural risk is very high and that interventions are necessary to protect surgeon musculoskeletal health for optimal surgeon performance and career longevity.
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| 20. |
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| 21. |
- Barragan, Antonio, et al.
(författare)
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GABAergic signalling in the immune system
- 2015
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 213:4, s. 819-827
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Forskningsöversikt (refereegranskat)abstract
- The GABAergic system is the main inhibitory neurotransmitter system in the central nervous system (CNS) of vertebrates. Signalling of the transmitter c-aminobutyric acid (GABA) via GABA type A receptor channels or G-protein-coupled type B receptors is implicated in multiple CNS functions. Recent findings have implicated the GABAergic system in immune cell functions, inflammatory conditions and diseases in peripheral tissues. Interestingly, the specific effects may vary between immune cell types, with stage of activation and be altered by infectious agents. GABA/GABA-A receptor-mediated immunomodulatory functions have been unveiled in immune cells, being present in T lymphocytes and regulating the migration of Toxoplasma-infected dendritic cells. The GABAergic system may also play a role in the regulation of brain resident immune cells, the microglial cells. Activation of microglia appears to regulate the function of GABAergic neurotransmission in neighbouring neurones through changes induced by secretion of brain-derived neurotrophic factor. The neurotransmitter-driven immunomodulation is a new but rapidly growing field of science. Herein, we review the present knowledge of the GABA signalling in immune cells of the periphery and the CNS and raise questions for future research.
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| 22. |
- Barrett, Aidan, et al.
(författare)
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Physiological estrogen levels are dispensable for the sex difference in immune responses during allergen-induced airway inflammation
- 2023
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 228:3
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Tidskriftsartikel (refereegranskat)abstract
- Women show an increased prevalence of adult-onset asthma compared to men and previous studies have shown that testosterone inhibits while estrogen worsens allergen-induced airway inflammation. However, detailed knowledge about the aggravating effects of estrogen on immune responses remain unclear. Defining the effects of physiological levels of estrogen on immune responses in asthma would aid in the development of improved treatment strategies.In this study, the importance of estrogen for the sex difference in asthma was determined using a murine model of house dust mite (HDM)-induced airway inflammation on intact female and male mice, as well as on ovariectomized (OVX) female mice treated with a physiological dose of 17 beta-estradiol (E2). Innate and adaptive immune responses were defined in bronchoalveolar lavage fluid, mediastinal lymph node (mLN) and lung tissue.The results reveal increased numbers of lung eosinophils, macrophages, and dendritic cells in female but not in male mice after HDM challenge. Females also exhibit higher numbers of Th17 cells in both mLN and lung in response to HDM. However, treatment of OVX mice with physiological levels of E2 does not influence any of the analyzed cell populations.Together, this study confirms the previously reported sex difference in allergen-induced airway inflammation and show that female mice mount stronger innate and adaptive immune responses to HDM challenge, but these effects are not mediated by physiological levels of E2.
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| 23. |
- Bujila, Ioana, et al.
(författare)
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Malaria-derived hemozoin exerts early modulatory effects on the phenotype and maturation of human dendritic cells
- 2016
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 18:3, s. 413-423
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Tidskriftsartikel (refereegranskat)abstract
- Plasmodium falciparum (P. falciparum)-induced effects on the phenotype of human dendritic cells (DC) could contribute to poor induction of long-lasting protective immunity against malaria. DC ability to present antigens to naïve T cells, thus initiating adaptive immune responses depends on complex switches in chemokine receptors, production of soluble mediators and expression of molecules enabling antigen-presentation and maturation. To examine the cellular basis of these processes in the context of malaria, we performed detailed analysis of early events following exposure of human monocyte-derived DC to natural hemozoin (nHZ) and the synthetic analog of its heme core, β-hematin. DC exposed to either molecule produced high levels of the inflammatory chemokine MCP-1, showed continuous high expression of the inflammatory chemokine receptor CCR5, no upregulation of the lymphoid homing receptor CCR7 and no cytoskeletal actin redistribution with loss of podosomes. DC partially matured as indicated by increased expression of major histocompatibility complex (MHC) class II and CD86 following nHZ and β-hematin exposure, however there was a lack in expression of the maturation marker CD83 following nHZ but not β-hematin exposure. Overall our data demonstrate that exposure to nHZ partially impairs the capacity of DC to mature, an effect in part differential to β-hematin.
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| 24. |
- Jakobsson, Martin, et al.
(författare)
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Ryder Glacier in northwest Greenland is shielded from warm Atlantic water by a bathymetric sill
- 2020
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- The processes controlling advance and retreat of outlet glaciers in fjords draining the Greenland Ice Sheet remain poorly known, undermining assessments of their dynamics and associated sea-level rise in a warming climate. Mass loss of the Greenland Ice Sheet has increased six-fold over the last four decades, with discharge and melt from outlet glaciers comprising key components of this loss. Here we acquired oceanographic data and multibeam bathymetry in the previously uncharted Sherard Osborn Fjord in northwest Greenland where Ryder Glacier drains into the Arctic Ocean. Our data show that warmer subsurface water of Atlantic origin enters the fjord, but Ryder Glacier’s floating tongue at its present location is partly protected from the inflow by a bathymetric sill located in the innermost fjord. This reduces under-ice melting of the glacier, providing insight into Ryder Glacier’s dynamics and its vulnerability to inflow of Atlantic warmer water.
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| 25. |
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