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- Bernatsky, Sasha, et al.
(författare)
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Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma
- 2017
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
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- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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- Bratanis, Eleni, et al.
(författare)
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BspK, a serine protease from the predatory bacterium Bdellovibrio bacteriovorus with utility for analysis of therapeutic antibodies
- 2017
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Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 83:4
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Tidskriftsartikel (refereegranskat)abstract
- The development of therapeutic and diagnostic antibodies is a rapidly growing field of research, being the fastest expanding group of products on the pharmaceutical market, and appropriate quality controls are crucial for their application. We have identified and characterized the serine protease termed BspK (Bdellovibrio serine protease K) from Bdellovibrio bacteriovorus and here show its activity on antibodies. Mutation of the serine residue at position 230 rendered the protease inactive. Further investigations of BspK enzymatic characteristics revealed autoproteolytic activity, resulting in numerous cleavage products. Two of the autoproteolytic cleavage sites in the BspK fusion protein were investigated in more detail and corresponded to cleavage after K28 and K210 in the N- and C-terminal parts of BspK, respectively. Further, BspK displayed stable enzymatic activity on IgG within the pH range of 6.0 to 9.5 and was inhibited in the presence of ZnCl2. BspK demonstrated preferential hydrolysis of human IgG1 compared to other immunoglobulins and isotypes, with hydrolysis of the heavy chain at position K226 generating two separate Fab fragments and an intact IgG Fc domain. Finally, we show that BspK preferentially cleaves its substrates C-terminally to lysines similar to the protease LysC. However, BspK displays a unique cleavage profile compared to several currently used proteases on the market.
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- Hoshino, Ayuko, et al.
(författare)
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Tumour exosome integrins determine organotropic metastasis
- 2015
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 527:7578, s. 329-
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Tidskriftsartikel (refereegranskat)abstract
- Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver-and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
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- Lood, Rolf, et al.
(författare)
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Determining bacteriophage endopeptidase activity using either fluorophore-quencher labeled peptides combined with liquid chromatography-mass spectrometry (LC-MS) or Förster resonance energy transfer (FRET) assays
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- The necessity of identifying novel methods to combat infections caused by antibiotic resistant bacteria is increasing each year. Recent advancements in the development of peptidoglycan hydrolases (e.g. lysins) from bacterial viruses (bacteriophages) have revealed the efficiency of this class of enzymes in treating serious bacterial infections. Though promising results have been obtained regarding the lethal action of lysin on bacterial pathogens both in vitro and in vivo, an often-overlooked factor in these studies is precisely identifying their peptidoglycan cleavage site. This knowledge would be useful for following the activity of the enzyme during development, without the need for whole-organism lytic assays. However, more importantly, it would enable the selection of lysins with different cleavage activities that would act synergistically for enhanced efficacy. Here, we have developed two new methods to accurately identify the cleavage site of lysins using liquid chromatography mass spectrometry (LC-MS) on peptidoglycan-like fluorophore-quencher modified synthetic peptides, as well as determining the enzymatic action and kinetics of the enzymes on modified peptides in a FoÈrster resonance energy transfer (FRET) assay. These methods should facilitate progress within the lysin field, accelerating the development of therapeutic lysins to combat antibiotic resistant bacterial infections.
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| 17. |
- Machiela, Mitchell J., et al.
(författare)
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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
- 2016
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:8, s. 1663-1676
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Tidskriftsartikel (refereegranskat)abstract
- Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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| 18. |
- Molina-Besch, Katrin, et al.
(författare)
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A Supply Chain Perspective on Green Packaging Development -Theory Versus Practice
- 2016
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Ingår i: Packaging Technology & Science. - : Wiley. - 0894-3214. ; 29:1, s. 45-63
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this paper is to provide insight into how companies work during packaging development to reduce negative environmental impact along supply chains, and to compare their practical approaches with the theoretical concepts presented in the literature. The research approach is explorative and based on nine cases in the food and manufacturing industries in Sweden. Data were collected from the managerial perspectives of the packaging manager, the logistics manager and the environmental manager. The findings indicate that companies commonly apply a variety of green packaging approaches with a focus on approaches with clear economic benefits. Moreover, companies seem to lack guidance on how to handle trade-offs and are unable to fully utilize the theoretical environmental benefits of green packaging approaches because of internal and external barriers. The paper presents five propositions regarding to what extent the theoretical green packaging concepts are applied in practice. To address the gap between theory and practice companies should: develop packaging solutions that contribute to a reduction of environmental impact from the consumer phase (for example through improved apportionment, user-friendly and informative packaging); use local packaging adaptation as a strategy to address geographically varying transport, handling and waste management conditions; replace brand recognition through packaging size and shape with graphic design, high-quality materials and printing. The results confirm that internal and external collaborations are important requirements for successful green packaging development. Copyright (c) 2015 John Wiley & Sons, Ltd.
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| 22. |
- Pålsson, Henrik, et al.
(författare)
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A quantitative study of energy consumption factors for three types of distribution channels
- 2017
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Konferensbidrag (refereegranskat)abstract
- PurposeThe purpose of this paper is to analyse the impact of six energy consumption factors (unsold products, product returns, packaging, freight transport, passenger transport and buildings) on the total energy consumption in three types of distribution channels for e-commerce and conventional trade.Design/methodology/approachThe study uses a quantitative calculation model where input data for the energy factors can be varied. The model is used to calculate the energy consumption for six IKEA products, four textile products (based on the supply chain of Nudie Jeans) and books, which were early e-commerce products. It calculates and compares the energy consumption in distribution via a store, a pick-up point and home delivery for six energy consumption factors. Data are collected from various sources, such as archival data, NTM, Swedish Transport Administration, Ecoinvent and SimaPro. In the calculations, a baseline scenario is first outlined for each product based on the current supply chain and product characteristics. Second, the baseline scenario is compared to a time optimisation scenario and an energy minimisation scenario. Third, the impact of the energy consumption factors on the total energy consumption in different distribution channels are analysed. FindingsThe findings shows the relative importance of six energy consumption factors (unsold products, product returns, packaging, freight transport, passenger transport and buildings) on the total energy consumption in distribution systems with home delivery, pick-up points and store sales for various types of products. It also discusses the importance of each energy consumption factor in the three types of distribution channels. Furthermore, by analysing the freight transport factor, we get insights into energy differences in global and domestic supply chains.Research limitations/implications The paper study retail and textile products as well as books in three supply chains.Practical implicationsThe findings can help supply chain managers in 1) selecting environmentally efficient distribution systems (home delivery, pick-up point or store) and 2) to prioritise work efforts between the six energy consumption factors within each distribution system to reduce total energy consumption.Original/valueThe paper provides new insights into both relative and absolute effects of unsold products, product returns, packaging, freight transport, passenger transport and buildings on the total energy consumption of three types of distribution channels for e-commerce and conventional trade.
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