| 21. |
- Ali, Ahmed, et al.
(författare)
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Single cell metabolism : current and future trends
- 2022
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 18:10
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Forskningsöversikt (refereegranskat)abstract
- Single cell metabolomics is an emerging and rapidly developing field that complements developments in single cell analysis by genomics and proteomics. Major goals include mapping and quantifying the metabolome in sufficient detail to provide useful information about cellular function in highly heterogeneous systems such as tissue, ultimately with spatial resolution at the individual cell level. The chemical diversity and dynamic range of metabolites poses particular challenges for detection, identification and quantification. In this review we discuss both significant technical issues of measurement and interpretation, and progress toward addressing them, with recent examples from diverse biological systems. We provide a framework for further directions aimed at improving workflow and robustness so that such analyses may become commonly applied, especially in combination with metabolic imaging and single cell transcriptomics and proteomics.
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| 22. |
- Bachelet, Delphine, et al.
(författare)
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Occurrence of Anti-Drug Antibodies against Interferon-Beta and Natalizumab in Multiple Sclerosis : A Collaborative Cohort Analysis
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Immunogenicity of biopharmaceutical products in multiple sclerosis is a frequent side effect which has a multifactorial etiology. Here we study associations between anti-drug antibody (ADA) occurrence and demographic and clinical factors. Retrospective data from routine ADA test laboratories in Sweden, Denmark, Austria and Germany (Dusseldorf group) and from one research study in Germany (Munich group) were gathered to build a collaborative multi-cohort dataset within the framework of the ABIRISK project. A subset of 5638 interferon-beta (IFN beta)-treated and 3440 natalizumab-treated patients having data on at least the first two years of treatment were eligible for interval-censored time-to-event analysis. In multivariate Cox regression, IFN beta-1a subcutaneous and IFN beta-1b subcutaneous treated patients were at higher risk of ADA occurrence compared to IFN beta-1a intramuscular-treated patients (pooled HR = 6.4, 95% CI 4.9-8.4 and pooled HR = 8.7, 95% CI 6.6-11.4 respectively). Patients older than 50 years at start of IFN beta therapy developed ADA more frequently than adult patients younger than 30 (pooled HR = 1.8, 95% CI 1.4-2.3). Men developed ADA more frequently than women (pooled HR = 1.3, 95% CI 1.1-1.6). Interestingly we observed that in Sweden and Germany, patients who started IFN beta in April were at higher risk of developing ADA (HR = 1.6, 95% CI 1.1-2.4 and HR = 2.4, 95% CI 1.5-3.9 respectively). This result is not confirmed in the other cohorts and warrants further investigations. Concerning natalizumab, patients older than 45 years had a higher ADA rate (pooled HR = 1.4, 95% CI 1.0-1.8) and women developed ADA more frequently than men (pooled HR = 1.4, 95% CI 1.0-2.0). We confirmed previously reported differences in immunogenicity of the different types of IFN beta. Differences in ADA occurrence by sex and age are reported here for the first time. These findings should be further investigated taking into account other exposures and biomarkers.
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| 23. |
- Blasiak, Robert, et al.
(författare)
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Towards greater transparency and coherence in funding for sustainable marine fisheries and healthy oceans
- 2019
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Ingår i: Marine Policy. - : Elsevier BV. - 0308-597X .- 1872-9460. ; 107
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Tidskriftsartikel (refereegranskat)abstract
- This final manuscript in the special issue on Funding for ocean conservation and sustainable fisheries is the result of a dialogue aimed at connecting lead authors of the special issue manuscripts with relevant policymakers and practitioners. The dialogue took place over the course of a two-day workshop in December 2018, and this coda manuscript seeks to distil thinking around a series of key recurring topics raised throughout the workshop. These topics are collected into three broad categories, or needs: 1) a need for transparency, 2) a need for coherence, and 3) a need for improved monitoring of project impacts. While the special issue sought to collect new research into the latest trends and developments in the rapidly evolving world of funding for ocean conservation and sustainable fisheries, the insights collected during the workshop have helped to highlight remaining knowledge gaps. Therefore, each of the three needs identified within this manuscript is followed by a series of questions that the workshop participants identified as warranting further attention as part of a future research agenda. The crosscutting nature of many of the issues raised as well as the rapid pace of change that characterizes this funding landscape both pointed to a broader need for continued dialogue and study that reaches across the communities of research, policy and practice.
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| 24. |
- Davidson, Iain F., et al.
(författare)
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Rapid movement and transcriptional re-localization of human cohesin on DNA
- 2016
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Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 35:24, s. 2671-2685
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Tidskriftsartikel (refereegranskat)abstract
- The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA. It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown. Here, we used single-molecule imaging to show that cohesin can diffuse rapidly on DNA in a manner consistent with topological entrapment and can pass over some DNA-bound proteins and nucleosomes but is constrained in its movement by transcription and DNA-bound CCCTC-binding factor (CTCF). These results indicate that cohesin can be positioned in the genome by moving along DNA, that transcription can provide directionality to these movements, that CTCF functions as a boundary element for moving cohesin, and they are consistent with the hypothesis that cohesin spatially organizes the genome via loop extrusion.
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| 25. |
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| 26. |
- Fioretos, Michael, et al.
(författare)
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Hospital admissions in two European landscapes - comparison between Heraklion, Greece and Linköping
- 1993
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Ingår i: International Journal of Health Sciences. - 0924-2287. ; 4, s. 33-39
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Tidskriftsartikel (refereegranskat)abstract
- The study describes a comparison of hospital admissions during a two-year period between a regional hospital in Heraklion (Greece) and a regional hospital in Linköping (Sweden). The findings are considered mainly in terms of health care delivery and utilization in relation to various types of demographic factors.The results indicate that despite the different cultural and socio-economic environments in the studied districts, there are important similarities of hospitalisation pattern in the urban areas. However, there are also notable differences. The hospitalisation pattern seems to be more equally distributed between sexes and between urban and rural areas in Linköping (Sweden) than in Heraklion (Greece), where it appeared that the rural population, and women in particular, did not get hospital care according to their needs.
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| 27. |
- Frost, Steven A, et al.
(författare)
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Unplanned admission to the intensive care unit in the very elderly and risk of in-hospital mortality.
- 2010
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Ingår i: Critical care and resuscitation. - 1441-2772. ; 12:3, s. 171-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Unplanned admission to the intensive care unit has been shown to significantly increase the risk of inhospital mortality. Medical advances and increased expectations have resulted in a greater number of very elderly patients (80 years and over) being admitted to the ICU. The risk of in-hospital death associated with unplanned admission to the ICU in very elderly patients has not been clearly defined. OBJECTIVE: To estimate the risk of in-hospital mortality associated with unplanned admission to the ICU in patients aged 80 years and over. DESIGN, SETTING AND PARTICIPANTS: Retrospective review of an adult intensive care database. The setting was Liverpool Hospital, a large teaching hospital in Sydney, Australia, with a 28-bed ICU that has about 2000 admissions per year. We analysed data on very elderly patients (n = 1680), aged 80 years or more, admitted to the ICU between 1 January 1997 and 31 December 2007. MAIN OUTCOME MEASURES: Baseline risk factors for inhospital mortality. RESULTS: Mortality among patients with unplanned ICU admissions was 47%, compared with 25% in patients with planned admissions (adjusted rate ratio [RR], 1.92 [95% CI, 1.59-2.32]). An estimated 50% of the overall risk of inhospital death among very elderly patients was attributable to a combination of unplanned admission to the ICU, the presence of at least one comorbid condition, acute renal failure and respiratory failure requiring intubation. CONCLUSION: Unplanned admission to the ICU increases the risk of in-hospital mortality in very elderly patients. At least 50% of the risk of in-hospital death in this age group is attributable to a combination of unplanned ICU admission, comorbidity (≥1 comorbid condition), acute renal failure and respiratory failure.
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| 28. |
- Gould, Cathryn M, et al.
(författare)
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ELM : the status of the 2010 eukaryotic linear motif resource.
- 2010
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 38
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Tidskriftsartikel (refereegranskat)abstract
- Linear motifs are short segments of multidomain proteins that provide regulatory functions independently of protein tertiary structure. Much of intracellular signalling passes through protein modifications at linear motifs. Many thousands of linear motif instances, most notably phosphorylation sites, have now been reported. Although clearly very abundant, linear motifs are difficult to predict de novo in protein sequences due to the difficulty of obtaining robust statistical assessments. The ELM resource at http://elm.eu.org/ provides an expanding knowledge base, currently covering 146 known motifs, with annotation that includes >1300 experimentally reported instances. ELM is also an exploratory tool for suggesting new candidates of known linear motifs in proteins of interest. Information about protein domains, protein structure and native disorder, cellular and taxonomic contexts is used to reduce or deprecate false positive matches. Results are graphically displayed in a 'Bar Code' format, which also displays known instances from homologous proteins through a novel 'Instance Mapper' protocol based on PHI-BLAST. ELM server output provides links to the ELM annotation as well as to a number of remote resources. Using the links, researchers can explore the motifs, proteins, complex structures and associated literature to evaluate whether candidate motifs might be worth experimental investigation.
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| 29. |
- Grimm, Melissa J, et al.
(författare)
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Monocyte- and macrophage-targeted NADPH oxidase mediates antifungal host defense and regulation of acute inflammation in mice
- 2013
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 190:8, s. 4175-4184
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Tidskriftsartikel (refereegranskat)abstract
- Chronic granulomatous disease, an inherited disorder of the NADPH oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. Although NADPH oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where NADPH oxidase has been deemed vital for pathogen killing. In contrast, the function and importance of NADPH oxidase in macrophages are less clear. Therefore, we evaluated susceptibility to pulmonary aspergillosis in globally NADPH oxidase-deficient mice versus transgenic mice with monocyte/macrophage-targeted NADPH oxidase activity. We found that the lethal inoculum was >100-fold greater in transgenic versus globally NADPH oxidase-deficient mice. Consistent with these in vivo results, NADPH oxidase in mouse alveolar macrophages limited germination of phagocytosed Aspergillus fumigatus spores. Finally, globally NADPH oxidase-deficient mice developed exuberant neutrophilic lung inflammation and proinflammatory cytokine responses to zymosan, a fungal cell wall-derived product composed principally of particulate beta-glucans, whereas inflammation in transgenic and wild-type mice was mild and transient. Taken together, our studies identify a central role for monocyte/macrophage NADPH oxidase in controlling fungal infection and in limiting acute lung inflammation. The Journal of Immunology, 2013, 190: 4175-4184.
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| 30. |
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