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- Burney, P., et al.
(författare)
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A case-control study of the relation between plasma selenium and asthma in European populations : a GAL2EN project
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 63:7, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.
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- Giovannucci, TA, et al.
(författare)
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Inhibition of the ubiquitin-proteasome system by an NQO1-activatable compound
- 2021
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:10, s. 914-
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Tidskriftsartikel (refereegranskat)abstract
- Malignant cells display an increased sensitivity towards drugs that reduce the function of the ubiquitin-proteasome system (UPS), which is the primary proteolytic system for destruction of aberrant proteins. Here, we report on the discovery of the bioactivatable compound CBK77, which causes an irreversible collapse of the UPS, accompanied by a general accumulation of ubiquitylated proteins and caspase-dependent cell death. CBK77 caused accumulation of ubiquitin-dependent, but not ubiquitin-independent, reporter substrates of the UPS, suggesting a selective effect on ubiquitin-dependent proteolysis. In a genome-wide CRISPR interference screen, we identified the redox enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) as a critical mediator of CBK77 activity, and further demonstrated its role as the compound bioactivator. Through affinity-based proteomics, we found that CBK77 covalently interacts with ubiquitin. In vitro experiments showed that CBK77-treated ubiquitin conjugates were less susceptible to disassembly by deubiquitylating enzymes. In vivo efficacy of CBK77 was validated by reduced growth of NQO1-proficient human adenocarcinoma cells in nude mice treated with CBK77. This first-in-class NQO1-activatable UPS inhibitor suggests that it may be possible to exploit the intracellular environment in malignant cells for leveraging the impact of compounds that impair the UPS.
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- Gunnbjornsdottir, M. I., et al.
(författare)
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Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms
- 2004
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Ingår i: Eur Respir J. - : European Respiratory Society (ERS). ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5-10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults.
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- Mubeen, Saad, et al.
(författare)
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Provisioning of Predictable Embedded Software in the Vehicle Industry : The Rubus Approach
- 2017
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Ingår i: Proceedings - 2017 IEEE/ACM 4th International Workshop on Software Engineering Research and Industrial Practice, SER and IP 2017. - : Institute of Electrical and Electronics Engineers Inc.. - 9781538627976 ; , s. 3-9
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Konferensbidrag (refereegranskat)abstract
- Providing computer-based services for vehicular systems has evolved to the point where majority of functions are realised by software. However, the need to provide safety in critical functions such as braking and engine control requires an approach that can guarantee reliable operation of the functions. At the same time, there are a variety of vehicle functions that are less critical. The main challenge for the vehicle manufacturers is to provide both types of functions in an economic and reliable manner. To meet this challenge, this paper considers the Rubus tool chain for model-and component-based development of vehicle software and a well-proven (in the industrial use for over twenty years) and certified (according to ISO 26262) real-time operating system for its execution. The paper provides an overview of the Rubus approach and driving concepts as well as the research results that are used in providing its tool chain. Moreover, the paper presents a success story of a unique academic-industrial collaboration in the vehicle domain that has resulted in sustained development of the tool chain. The collaborators form a clear value chain from academia, through tool developer, to the end users of the technology. The paper also highlights the perspectives of the collaborators and discusses the challenges faced, experiences gained and lessons learned from several technology transfer projects.
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- Roos, A., et al.
(författare)
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Stable High-Sensitivity Cardiac Troponin T Levels and Outcomes in Patients With Chest Pain
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 70:18, s. 2226-2236
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND There is a paucity of data on the association between high-sensitivity cardiac troponin (hs-cTn) levels and outcomes in patients with chest pain but no myocardial infarction (MI), or any other condition that may lead to acutely elevated troponin levels. OBJECTIVES The authors hypothesized that any detectable high-sensitivity cardiac troponin T (hs-cTnT) level is associated with adverse outcomes. METHODS All patients (N = 22,589)> 25 years of age with chest pain and hs-cTnT analyzed concurrently in the emergency department of Karolinska University Hospital, Stockholm, Sweden from 2011 to 2014 were eligible for inclusion. After excluding all patients with acute conditions that may have affected hs-cTnT, or MI associated with the visit, or insufficient information to determine whether troponin levels were stable, Cox regression was used to estimate risks for all-cause, cardiovascular, and noncardiovascular mortality, MI, and heart failure at different levels of troponins. RESULTS A total of 19,460 patients with a mean age of 54 +/- 17 years were included. During a mean follow-up of 3.3 +/- 1.2 years, 1,349 (6.9%) patients died. Adjusted hazard ratios (with 95% confidence intervals) for all-cause mortality were 2.00 (1.66 to 2.42), 2.92 (2.38 to 3.59), 4.07 (3.28 to 5.05), 6.77 (5.22 to 8.78), and 9.68 (7.18 to 13.00) in patients with hs-cTnT levels of 5 to 9, 10 to 14, 15 to 29, 30 to 49, and >= 50 ng/l, respectively, compared with patients with hs-cTnT levels < 5 ng/l. There was a strong and graded association between all detectable levels of hs-cTnT and risk for MI, heart failure, and cardiovascular and noncardiovascular mortality. CONCLUSIONS Among patients with chest pain and stable troponin levels, any detectable level of hs-cTnT is associated with an increased risk of death and cardiovascular outcomes and should merit further attention. (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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- Sowinska, A, et al.
(författare)
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Cleavage of HMGB1 by Proteolytic Enzymes Associated with Inflammatory Conditions
- 2020
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 11, s. 448262-
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular HMGB1 acts as an alarmin in multiple autoimmune diseases. While its release and functions have been extensively studied, there is a substantial lack of knowledge regarding HMGB1 regulation at the site of inflammation. Herein we show that enzymes present in arthritis-affected joints process HMGB1 into smaller peptides in vitro. Gel electrophoresis, Western blotting and mass spectrometry analyses indicate cleavage sites for human neutrophil elastase, cathepsin G, and matrix metalloproteinase 3 within the HMGB1 structure. While human neutrophil elastase and matrix metalloproteinase 3 might alter the affinity of HMGB1 to its receptors by cleaving the acidic C-terminal tail, cathepsin G rapidly and completely degraded the alarmin. Contrary to a previous report we demonstrate that HMGB1 is not a substrate for dipeptidyl peptidase IV. We also provide novel information regarding the presence of these proteases in synovial fluid of juvenile idiopathic arthritis patients. Correlation analysis of protease levels and HMGB1 levels in synovial fluid samples did not, however, reveal any direct relationship between the recorded levels. This study provides knowledge of proteolytic processing of HMGB1 relevant for the regulation of HMGB1 during inflammatory disease.
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- Antoniewicz, Lukasz, et al.
(författare)
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Electronic cigarettes increase endothelial progenitor cells in the blood of healthy volunteers
- 2016
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Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 255, s. 179-185
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The use of electronic cigarettes is increasing dramatically on a global scale and its effects on human health remain uncertain. In the present study, we measured endothelial progenitor cells (EPCs) and microvesicles (MVs) in healthy young volunteers following short-term exposure to inhalation of e-cigarette vapor (ECV) to determine vascular changes.Methods: Sixteen healthy seldom smokers were randomized into two groups either exposed or not exposed to 10 puffs of ECV for 10 min, in a crossover design. Blood samples were obtained at baseline and 1, 4 and 24 h following exposure. EPCs (CD34 + CD309) and MVs were analyzed by flow cytometry. MVs were phenotyped according to origin (platelet (CD41), endothelial (CD144), leukocytes (CD45), monocytes (CD14)) and nuclear content (SYTO 13 dye). In addition, expression of inflammation markers such P-selectin (CD62P), E-selectin (CD62E), CD40-ligand (CD154) and HMGB1 was investigated. Fractional exhaled nitric oxide (FeNO) was also measured at baseline and after 24 h.Results: EPC levels in blood were significantly increased 1 h following exposure to ECV and returned to baseline values after 24 h. Only E-selectin positive MVs (endothelial origin) were slightly elevated (p < 0.038). FeNO was unaffected by exposure to ECV. Conclusions: In healthy volunteers, ten puffs of e-cigarette vapor inhalation caused an increase in EPCs. This increase was of the same magnitude as following smoking of one traditional cigarette, as we previously demonstrated. Taken together, these results may represent signs of possible vascular changes after short e-cigarette inhalation. Further studies analyzing potential cardiovascular health effects are critical as the e-cigarette market continues to burgeon.
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