| 1. |
- Myrbeck, Åsa, et al.
(författare)
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Instruktion till provtagning och analys av stallgödsel
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report presents instructions for manure sampling and analysis produced within the project MANURE STANDARDS financed by Interreg Baltic Sea Region Programme (2014-2020). The project developed joint guidelines for taking representative manure samples, recommendations for manure analysis in the laboratories and a farm-level calculation tool for farm-specific manure mass balance calculation. All materials areavailable in English at: https://www.luke.fi/manurestandards/en/frontpage/
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| 2. |
- Pejlare, Johanna, 1976, et al.
(författare)
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On the relations between geometry and algebra in Gestrinius' edition of Euclid's Elements
- 2016
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Ingår i: Radford, L., Furinghetti, F., & Hausberger, T. (Eds.) (2016). Proceedings of the 2016 ICME Satellite Meeting of the International Study Group on the Relations Between the History and Pedagogy of Mathematics. Montpellier, France: IREM de Montpellier.. - 2909916510 ; , s. 513-523
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Konferensbidrag (refereegranskat)abstract
- In 1637 the Swedish mathematician Martinus Erici Gestrinius contributed with a commented edition of Euclid’s Elements. In this article we analyse the relationship between geometry and algebra in Gestrinius’ Elements, as presented in Book II. Of particular interest are Propositions 4, 5, and 6, dealing with straight lines cut into equal and unequal parts, and the three kinds of quadratic equations Gestrinius associates with them. We argue that Gestrinius followed Clavius translation of the Elements, but was influenced by Ramus to include algebra.
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| 3. |
- Rodhe, Johanna, et al.
(författare)
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Spatio-temporal activation of caspase-8 in myeloid cells upon ischemic stroke
- 2016
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 4, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Ischemic stroke (caused by thrombosis, embolism or vasoconstriction) lead to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral macrophages, which contribute to an inflammatory response involved in regulation of the neuronal damage. We showed earlier that upon pro-inflammatory stimuli, the orderly activation of caspase-8 and caspase-3/7 regulates microglia activation through a protein kinase C-δ dependent pathway. Here, we present in vivo evidence for the activation of caspase-8 and caspase-3 in microglia/macrophages in post-mortem tissue from human ischemic stroke subjects. Indeed, CD68-positive microglia/macrophages in the ischemic peri-infarct area exhibited significant expression of the cleaved and active form of caspase-8 and caspase-3. The temporal and spatial activation of caspase-8 was further investigated in a permanent middle cerebral artery occlusion mouse model of ischemic stroke. Increasing levels of active caspase-8 was found in Iba1-positive cells over time in the peri-infarct area, at 6, 24 and 48 h after artery occlusion. Analysis of post-mortem brain tissue from human subject who suffered two stroke events, referred as recent and old stroke, revealed that expression of cleaved caspase-8 and -3 in CD68-positive cells could only be found in the recent stroke area. Analysis of cleaved caspase-8 and -3 expressions in a panel of human stroke cases arranged upon days-after stroke and age-matched controls suggested that the expression of these caspases correlated with the time of onset of stroke. Collectively, these data illustrate the temporal and spatial activation of caspase-8 and -3 in microglia/macrophages occurring upon ischemic stroke and suggest that the expression of these caspases could be used in neuropathological diagnostic work.
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| 4. |
- Rodhe, Johanna
(författare)
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Studies on caspase signaling in microglia
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to investigate the roles of caspase-8 and caspase-3 in microglia and in brain disorders, beyond their function in apoptosis. Microglia are resident immune cells of the central nervous system and act as the first line of defense against invading pathogens and other types of brain insults. They are important for normal brain homeostasis and can get rapidly activated upon infection or damage in the brain. However, dysregulated and overactivated microglia have also been reported to cause neurotoxicity and can further contribute to the damage in neurodegenerative diseases. Caspases are a family of proteases that are important for signaling pathways controlling cell death, inflammation, proliferation and differentiation. Caspase-8 and -3 are well known for their functions in apoptosis, but can also be involved in other processes. We have earlier shown that upon pro-inflammatory stimuli, microglia activate caspase-8 and -3/7 which regulate their activation through a PKCδ-dependent pathway, without triggering of cell death. In the first paper we investigate why caspase-3 under some circumstances kills the cells, but under others, like activation of microglia, does not. We show that upon pro-inflammatory stimuli of microglia, cIAP2 regulates the processing of caspase-3 so that it remains in the cytoplasm. Under cell death conditions caspase-3 can be fully processed and thereby enter the nucleus and exert its apoptotic functions. In order to provide genetic evidence of caspase control of microglia activation, we have created a model in which caspase-8 is conditionally knocked out in microglia. The CASP8 knock-out mice showed a reduction in pro-inflammatory activated microglia, which were associated with reduced neurotoxicity in a mouse model of Parkinson´s disease. We are also presenting data on the temporal and spatial activation of caspase-8 and -3 in microglia cells in human subjects who suffered a stroke. In the last paper we screened for genes involved in the metabolism of amyloid precursor protein in patients with late-onset Alzheimer´s disease. Significant association was found for rare variants of CASP8 and late-onset of the disease. For two of the variants we performed functional studies, which indicated an altered caspase-8 protein expression and reduced enzymatic activity. In summary, we have provided genetic evidence for caspase regulation of microglia proinflammatory activation and described a mechanism for how caspases prevent killing of cells during activation. We also describe the expression pattern of caspases in microglia cells after stroke, and provide evidence of rare mutations in caspase-8 associated with late-onset Alzheimer´s disease.
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| 5. |
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| 6. |
- Shen, Xianli, et al.
(författare)
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Glioma-induced inhibition of caspase-3 in microglia promotes a tumor-supportive phenotype
- 2016
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:11, s. 1282-1290
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Tidskriftsartikel (refereegranskat)abstract
- Glioma cells recruit and exploit microglia (the resident immune cells of the brain) for their proliferation and invasion ability. The underlying molecular mechanism used by glioma cells to transform microglia into a tumor-supporting phenotype has remained elusive. We found that glioma-induced microglia conversion was coupled to a reduction in the basal activity of microglial caspase-3 and increased S-nitrosylation of mitochondria-associated caspase-3 through inhibition of thioredoxin-2 activity, and that inhibition of caspase-3 regulated microglial tumor-supporting function. Furthermore, we identified the activity of nitric oxide synthase 2 (NOS2, also known as iNOS) originating from the glioma cells as a driving stimulus in the control of microglial caspase-3 activity. Repression of glioma NOS2 expression in vivo led to a reduction in both microglia recruitment and tumor expansion, whereas depletion of microglial caspase-3 gene promoted tumor growth. Our results provide evidence that inhibition of the denitrosylation of S-nitrosylated procaspase-3 mediated by the redox protein Trx2 is a part of the microglial pro-tumoral activation pathway initiated by glioma cancer cells.
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| 7. |
- Thalén, Niklas, 1985-, et al.
(författare)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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| 8. |
- Thalén, Niklas, et al.
(författare)
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Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold
- 2024
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Ingår i: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 81, s. 157-166
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Tidskriftsartikel (refereegranskat)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.
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