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| 2. |
- Blank Savukinas, Ulrika, et al.
(författare)
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Signaling pathways governing stem cell fate.
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 111:2, s. 492-503
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Forskningsöversikt (refereegranskat)abstract
- Hematopoietic stem cells (HSCs) are historically the most thoroughly characterized type of adult stem cell, and the hematopoietic system has served as a principal model structure of stem-cell biology for several decades. However, paradoxically, although HSCs can be defined by function and even purified to near-homogeneity, the intricate molecular machinery and the signaling mechanisms regulating fate events, such as self-renewal and differentiation, have remained elusive. Recently, several developmentally conserved signaling pathways have emerged as important control devices of HSC fate, including Notch, Wingless-type (Wnt), Sonic hedgehog (Shh), and Smad pathways. HSCs reside in a complex environment in the bone marrow, providing a niche that optimally balances signals that control self-renewal and differentiation. These signaling circuits provide a valuable structure for our understanding of how HSC regulation occurs, concomitantly with providing information of how the bone marrow microenvironment couples and integrates extrinsic with intrinsic HSC fate determinants. It is the focus of this review to highlight some of the most recent developments concerning signaling pathways governing HSC fate.
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| 3. |
- Blank Savukinas, Ulrika, et al.
(författare)
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Smad7 promotes self-renewal of hematopoietic stem cells in vivo.
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 108:13, s. 4246-4254
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Tidskriftsartikel (refereegranskat)abstract
- The Smad-signaling pathway downstream of the transforming growth factor–beta superfamily of ligands is an evolutionarily conserved signaling circuitry with critical functions in a wide variety of biologic processes. To investigate the role of this pathway in the regulation of hematopoietic stem cells (HSCs), we have blocked Smad signaling by retroviral gene transfer of the inhibitory Smad7 to murine HSCs. We report here that the self-renewal capacity of HSCs is promoted in vivo upon blocking of the entire Smad pathway, as shown by both primary and secondary bone marrow (BM) transplantations. Importantly, HSCs overexpressing Smad7 have an unperturbed differentiation capacity as evidenced by normal contribution to both lymphoid and myeloid cell lineages, suggesting that the Smad pathway regulates self-renewal independently of differentiation. Moreover, phosphorylation of Smads was inhibited in response to ligand stimulation in BM cells, thus verifying impairment of the Smad-signaling cascade in Smad7-overexpressing cells. Taken together, these data reveal an important and previously unappreciated role for the Smad-signaling pathway in the regulation of self-renewal of HSCs in vivo.
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| 6. |
- Grahn, Evastina, et al.
(författare)
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Historical pollution of seldom monitored trace elements in Sweden : Part B: sediment analysis of silver, antimony, thallium and indium
- 2006
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Ingår i: Journal of Environmental Monitoring. - 1464-0325 .- 1464-0333. ; 8:7, s. 732-744
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Tidskriftsartikel (refereegranskat)abstract
- Sediment cores from four boreal and remote lakes in a south to north transect in central Sweden were analysed for acid leachable silver, antimony, thallium and indium in the solid sediment phase and the corresponding porewater. Dating of the cores was made by their content of acid leachable lead and the 206Pb/207Pb ratio, in one lake also by 210Pb. The impact of diagenesis on element redistribution in the sediments was included and found to be minor except for thallium. The results show lowered concentrations towards the north and most intense accumulation after the Second World War, which is taken as evidence for atmospheric deposition being the primary source. Indium has declining concentrations in recent strata while silver and antimony increase. Thallium has lowered acid-leachable concentrations in recent strata. For all metals the impact of domestic industrialisation as well as the early industrialisation of central Europe is discernible. Only thallium appears to reach a geological background at depths that correspond to the late 18th century. For the other metals elevated levels are concluded.
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| 8. |
- Karlsson, Göran, et al.
(författare)
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Smad4 is critical for self-renewal of hematopoietic stem cells.
- 2007
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 204:3, s. 467-474
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Tidskriftsartikel (refereegranskat)abstract
- Members of the transforming growth factor β (TGF-β) superfamily of growth factors have been shown to regulate the in vitro proliferation and maintenance of hematopoietic stem cells (HSCs). Working at a common level of convergence for all TGF-β superfamily signals, Smad4 is key in orchestrating these effects. The role of Smad4 in HSC function has remained elusive because of the early embryonic lethality of the conventional knockout. We clarify its role by using an inducible model of Smad4 deletion coupled with transplantation experiments. Remarkably, systemic induction of Smad4 deletion through activation of MxCre was incompatible with survival 4 wk after induction because of anemia and histopathological changes in the colonic mucosa. Isolation of Smad4 deletion to the hematopoietic system via several transplantation approaches demonstrated a role for Smad4 in the maintenance of HSC self-renewal and reconstituting capacity, leaving homing potential, viability, and differentiation intact. Furthermore, the observed down-regulation of notch1 and c-myc in Smad4−/− primitive cells places Smad4 within a network of genes involved in the regulation HSC renewal.
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| 9. |
- Karlsson, Lena, et al.
(författare)
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Testimonies in Limbo? Swedish News Media’s Framing of Digital Campaigns Against Sexual Violence
- 2019
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Ingår i: Rape Narratives in Motion. - Cham : Springer International Publishing. - 9783030138516 - 9783030138523 ; , s. 223-245
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In her chapter, Karlsson explores the mainstream media reception of three mainly digital Swedish campaigns against sexual violence between 2010-2013: ##prataomdet/talkaboutit, #mörkertalet/the darkfigures, and #fatta/getit. She traces the ways in which the campaign lines of contention and the campaign testimonies are re-framed for new audiences by mainstream media. By mainly investigating headlines and the politics of quotation, Karlsson shows how some testimonial narratives from the campaigns are presented as generalizable, nationally relevant concerns whereas others are presented as minority concerns and how these representational politics are classed and raced.
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