| 1. |
- Amara, Umme, et al.
(author)
-
Molecular Intercommunication between the Complement and Coagulation Systems
- 2010
-
In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 185:9, s. 5628-5636
-
Journal article (peer-reviewed)abstract
- The complement system as well as the coagulation system has fundamental clinical implications in the context of life-threatening tissue injury and inflammation. Associations between both cascades have been proposed, but the precise molecular mechanisms remain unknown. The current study reports multiple links for various factors of the coagulation and fibrinolysis cascades with the central complement components C3 and C5 in vitro and ex vivo. Thrombin, human coagulation factors (F) XIa, Xa, and IXa, and plasmin were all found to effectively cleave C3 and C5. Mass spectrometric analyses identified the cleavage products as C3a and C5a, displaying identical molecular weights as the native anaphylatoxins C3a and C5a. Cleavage products also exhibited robust chemoattraction of human mast cells and neutrophils, respectively. Enzymatic activity for C3 cleavage by the investigated clotting and fibrinolysis factors is defined in the following order: FXa > plasmin > thrombin > FIXa > FXIa > control. Furthermore, FXa-induced cleavage of C3 was significantly suppressed in the presence of the selective FXa inhibitors fondaparinux and enoxaparin in a concentration-dependent manner. Addition of FXa to human serum or plasma activated complement ex vivo, represented by the generation of C3a, C5a, and the terminal complement complex, and decreased complement hemolytic serum activity that defines exact serum concentration that results in complement-mediated lysis of 50% of sensitized sheep erythrocytes. Furthermore, in plasma from patients with multiple injuries (n = 12), a very early appearance and correlation of coagulation (thrombin-antithrombin complexes) and the complement activation product C5a was found. The present data suggest that coagulation/fibrinolysis proteases may act as natural C3 and C5 convertases, generating biologically active anaphylatoxins, linking both cascades via multiple direct interactions in terms of a complex serine protease system. The Journal of Immunology, 2010, 185: 5628-5636.
|
|
| 2. |
- Fischer, Silvia, et al.
(author)
-
Extracellular RNA Liberates Tumor Necrosis Factor-alpha to Promote Tumor Cell Trafficking and Progression
- 2013
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 73:16, s. 5080-5089
-
Journal article (peer-reviewed)abstract
- Extracellular RNA (eRNA) released from injured cells promotes tissue permeability, thrombosis, and inflammation in vitro and in vivo, and RNase1 pretreatment can reduce all these effects. In this study, we investigated the role of the eRNA/RNase1 system in tumor progression and metastasis. Under quiescent and stimulatory conditions, tumor cells released much higher levels of endogenous extracellular RNA (eRNA) than nontumor cells. In glioblastomas, eRNA was detected at higher levels in tumors than nontumor tissue. eRNA induced tumor cells to adhere to and migrate through human cerebral microvascular endothelial cells (HCMEC/D3), in a manner requiring activation of VEGF signaling. In addition, eRNA liberated TNF-alpha from macrophages in a manner requiring activation of the TNF-alpha-converting enzyme TACE. Accordingly, supernatants derived from eRNA-treated macrophages enhanced tumor cell adhesion to HCMEC/D3. TNF-alpha release evoked by eRNA relied upon signaling activation of mitogen-activated protein kinases and the NF-kappa B pathway. In subcutaneous xenograft models of human cancer, administration of RNase1 but not DNase decreased tumor volume and weight. Taken together, these results suggest that eRNA released from tumor cells has the capacity to promote tumor cell invasion through endothelial barriers by both direct and indirect mechanisms, including through a mechanism involving TNF-alpha release from tumor-infiltrating monocytes/macrophages. Our findings establish a crucial role for eRNA in driving tumor progression, and they suggest applications for extracellular RNase1 as an antiinvasive regimen for cancer treatment.
|
|
| 3. |
- Humar, Miha, et al.
(author)
-
Introduction of the COST FP 1303 Cooperative Performance Test
- 2015
-
In: Proceedings of the 46th IRG Annual Meeting.
-
Conference paper (peer-reviewed)abstract
- COST Action FP 1303 “Performance of bio-based building materials” successfully started in October 2013 and an ambitious program was set up for the four year programme. COST Actions provide an excellent opportunity for collaborative research, e.g. in the frame of Round Robin tests.The idea of this respective test was to distribute a fairly simple test set up to as many places in Europe as possible in order to collect performance data reflecting the range of climatic exposure conditions. Furthermore we wanted to consider performance in its manifold meaning, i.e. optical, aesthetical, moisture and functional performance and durability. In contrast to traditional Round Robin tests aiming on comparative evaluation and validation of results from different test laboratories, this initiative aims on collecting performance data under climatically different exposure conditions. Therefore it was required to provide weather data from the respective test sites to allow establishing relationships between climate conditions and the following measured, which shall be evaluated regularly: decay, discolouration, development of mould and other staining fungi, corrosion, formation of cracks and moisture performance (if data logging device is included). Further details about the test and the first outcomes are presented in this paper.
|
|
| 4. |
- Magdalenić, Sanja, 1961-
(author)
-
Gendering the sociology profession : Sweden, Britain and the US
- 2004
-
Doctoral thesis (other academic/artistic)abstract
- The dissertation explores the relationship between gender and professions with a historical sociological analysis of the sociology profession in Sweden, Britain and the US. The theoretical framework draws upon three conceptual terrains: professions, organizations and gender. A variety of sources are utilized, such as published and unpublished material, interviews, available statistics, auto/biographies and archival material. The aim of the dissertation is twofold. First, it seeks to add to theorizing about the relationship between gender and professions by exploring the ways in which the emergence, organization of and knowledge production in an academic profession interrelates with gender. Second, the dissertation considers how gender is interrelated with the historical development of sociology as a profession.A revised concept of the “professional project” - which involves historically specific strategies of occupational closure - is used as an analytical tool to examine gendered processes of exclusion and demarcation that occurred in the three national histories of sociology. The dissertation considers three dimensions that are central to that framework of analysis - professional associations, academic departments and sociological canon – to explore how the restructuring of gender relations varied in different organizational spheres and over time.Although both women and men were involved in the sociological movement that preceded the emergence of the sociology profession, men came to dominate the institutional arenas such as sociology departments and professional associations. The conception of sociology as a field excluded the previous work of women, and some men, whose work did not fit the new agenda of objective science. Despite the fact that sociology as a profession institutionalised in different periods in Sweden, Britain and the US, until the late 1960s women were largely absent from higher posts in professional associations, sociology departments and the sociological canon. Also in all three sociology fields, there were social movements and women’s professional organizations that sought to bring women into the sociology profession and to put gender research on sociological agenda. Of the three arenas linked to the professional project, i. e. professional associations, academic departments and sociological canon, my analysis shows that women have made the greatest inroads in professional associations in terms of broadening the associations’ membership and representation as well as institutionalising gender caucuses and programs into the associations. Academic departments, where the production of future professionals and most knowledge takes place, have been slower to change. Finally, despite notable achievements in gendering sociological theory and research, gender has not yet become fully integrated into sociological canon.
|
|
