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- Deligny, Audrey, et al.
(författare)
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NDST2 (N-Deacetylase/N-Sulfotransferase-2) Enzyme Regulates Heparan Sulfate Chain Length
- 2016
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 291:36, s. 18600-18607
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of heparan sulfate synthesized by HEK 293 cells overexpressing murine NDST1 and/or NDST2 demonstrated that the amount of heparan sulfate was increased in NDST2-but not in NDST1-overexpressing cells. Altered transcript expression of genes encoding other biosynthetic enzymes or proteoglycan core proteins could not account for the observed changes. However, the role of NDST2 in regulating the amount of heparan sulfate synthesized was confirmed by analyzing heparan sulfate content in tissues isolated from Ndst2(-/-) mice, which contained reduced levels of the polysaccharide. Detailed disaccharide composition analysis showed no major structural difference between heparan sulfate from control and Ndst2(-/-) tissues, with the exception of heparan sulfate from spleen where the relative amount of trisulfated disaccharides was lowered in the absence of NDST2. In vivo transcript expression levels of the heparan sulfate-polymerizing enzymes Ext1 and Ext2 were also largely unaffected by NDST2 levels, pointing to a mode of regulation other than increased gene transcription. Size estimation of heparan sulfate polysaccharide chains indicated that increased chain lengths in NDST2-overexpressing cells alone could explain the increased heparan sulfate content. A model is discussed where NDST2-specific substrate modification stimulates elongation resulting in increased heparan sulfate chain length.
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| 2. |
- Fridholm, Tobias, 1980-
(författare)
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Working Together : Exploring Relational Tensions in Swedish Academia
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study explores the basic social conditions for high-quality university research, and focuses on research in science and technology in Sweden. Swedish research policy has adopted more of a market perspective on academic research and its role in society. This has meant the promotion of competition between researchers, increased focus on efficiency at universities, and attempts to make academia harmonize more with industry and other actors. How do such policies affect the variety of perspectives within the academic system? How do they affect the positions and identities of individual academics? These issues are discussed through the concept of "relational tensions". Relational tensions refer to social strains arising when interacting actors have different perspectives. Relational tensions can stimulate creativity, but may also cause unproductive conflicts. The discussion is underpinned by interviews with university researchers and a case study of Uppsala BIO-X, a program to commercialize university research in biotechnology. Typical cases of relational tensions are identified. These concern both interpersonal relations and differences between organized science and industry. A notable observation concerns potential frustration of individual academics, as competition and efficiency tends to make their positions and identities more contested. Researchers cope with relational tensions in three identified ways: socialization, seclusion, and lateral authority. Socialization is natural and often necessary, but reduces the variety of perspectives. Seclusion serves to retain variety and independence, but reduces interaction with others. Lateral authority is to formally or informally lend a researcher more authority, which improves the chance of maintaining a variety of perspectives without reducing interaction. The sustained usefulness of academic research arguably depends on its ability to foster and communicate a variety of perspectives. Hence, (i) promoting lateral authority seems fruitful within academia and in relations between academia and industry, and (ii) encouraging competition and efficiency may to some extent be counterproductive.
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| 5. |
- Faroldi, Gianni, et al.
(författare)
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ADAMTS: Novel proteases expressed by activated mast cells
- 2013
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Ingår i: Biological Chemistry. - : Walter de Gruyter GmbH. - 1431-6730 .- 1437-4315. ; 394, s. 291-305
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that mast cells (MCs) express the metalloproteases of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, and that ADAMTS expression is influenced by MC activation. Co-culture of MCs with live Gram-positive bacteria caused a profound induction of ADAMTS-9 and -6, as well as down-regulated expression of ADAMTS-5. Similar patterns were also seen after MC activation with calcium ionophore and by immunoglobulin E receptor crosslinking. Moreover, ADAMTS-5, -6 and -9 were all induced by activation of terminally differentiated murine peritoneal MCs and in a human MC line. ADAMTS-9 up-regulation in response to immunoglobulin E receptor crosslinking was strongly dependent on Go6976-sensitive protein kinase C and partly dependent on nuclear factor of activated T cells and nuclear factor kappa-light-chain-enhancer of activated B cells, respectively. The expression of ADAMTS-5, -6 and -9 was closely linked to MC maturation, as shown by their strong induction during the differentiation of bone marrow precursor cells into mature MCs. ADAMTS family members have been shown to possess aggrecanase activity. Accordingly, MCs were shown to express aggrecanase activity. Finally, ADAMTS-5 protein was detected in MCs by immunocytochemistry. Taken together, the present study reveals ADAMTS expression by MCs and that MC activation regulates the expression of these proteases, thus implicating the ADAMTS family of proteases in MC function.
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| 6. |
- Faroldi, Gianni, et al.
(författare)
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Nuclear Receptor 4a3 (Nr4a3) Regulates Murine Mast Cell Responses and Granule Content
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear receptor 4a3 (Nr4a3) is a transcription factor implicated in various settings such as vascular biology and inflammation. We have recently shown that mast cells dramatically upregulate Nuclear receptor 4a3 upon activation, and here we investigated the functional impact of Nuclear receptor 4a3 on mast cell responses. We show that Nuclear receptor 4a3 is involved in the regulation of cytokine/chemokine secretion in mast cells following activation via the high affinity IgE receptor. Moreover, Nuclear receptor 4a3 negatively affects the transcript and protein levels of mast cell tryptase as well as the mast cell's responsiveness allergen. Together, these findings identify Nuclear receptor 4a3 as a novel regulator of mast cell function.
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