| 1. |
- Bravi, Luca, et al.
(författare)
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Sulindac metabolites decrease cerebrovascular malformations in CCM3-knockout mice
- 2015
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:27, s. 8421-8426
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral cavernous malformation (CCM) is a disease of the central nervous system causing hemorrhage-prone multiple lumen vascular malformations and very severe neurological consequences. At present, the only recommended treatment of CCM is surgical. Because surgery is often not applicable, pharmacological treatment would be highly desirable. We describe here a murine model of the disease that develops after endothelial-cell-selective ablation of the CCM3 gene. We report an early, cell-autonomous, Wnt-receptor-independent stimulation of beta-catenin transcription activity in CCM3-deficient endothelial cells both in vitro and in vivo and a triggering of a beta-catenin-driven transcription program that leads to endothelial-tomesenchymal transition. TGF-beta/BMP signaling is then required for the progression of the disease. We also found that the anti-inflammatory drugs sulindac sulfide and sulindac sulfone, which attenuate beta-catenin transcription activity, reduce vascular malformations in endothelial CCM3-deficient mice. This study opens previously unidentified perspectives for an effective pharmacological therapy of intracranial vascular cavernomas.
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| 2. |
- Bagnara, Davide, et al.
(författare)
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Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of monoclonal CD5+ B cells with low surface immunoglobulins (IG). About 40% of CLL clones utilize quasi-identical B cell receptors, defined as stereotyped BCR. CLL-like stereotyped-IG rearrangements are present in normal B cells as a part of the public IG repertoire. In this study, we collected details on the representation and features of CLL-like stereotyped-IG in the IGH repertoire of B-cell subpopulations purified from the peripheral blood of nine healthy donors. The B-cell subpopulations were also fractioned according to the expression of surface CD5 molecules and IG light chain, IGκ and IGλ. IG rearrangements, obtained by high throughput sequencing, were scanned for the presence of CLL-like stereotyped-IG. CLL-like stereotyped-IG did not accumulate preferentially in the CD5+ B cells, nor in specific B-cell subpopulations or the CD5+ cell fraction thereof, and their distribution was not restricted to a single IG light chain type. CLL-like stereotyped-IG shared with the corresponding CLL stereotype rearrangements the IGHV mutational status. Instead, for other features such as IGHV genes and frequency, CLL stereotyped-IGs presented a CLL-like subset specific behavior which could, or could not, be consistent with CLL stereotyped-IGs. Therefore, as opposed to the immuno-phenotype, the features of the CLL stereotyped-IG repertoire suggest a CLL stereotyped subset-specific ontogeny. Overall, these findings suggest that the immune-genotype can provide essential details in tracking and defining the CLL cell of origin.
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| 3. |
- calefato, Caterina, 1980, et al.
(författare)
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Training designers for vulnerable generations: a quest for a more inclusive design
- 2014
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Ingår i: Interaction Design & Architechture. - 1826-9745 .- 2283-2998. ; :21, s. 25-36
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents findings from a project focusing on the specific needs of vulnerable generations - children and elderly people - in design teaching and training activities. The thirty-months project embodied a series of activities for developing, implementing and evaluating teaching materials focused on design for vulnerable generations, and identified two critical elements for the promotion of more inclusive design. First, knowledge and skills were identified through a collaborative process with stakeholders. We also applied in-depth data collection methods, surveys, interviews and case studies with experts and operators in relevant industry and research centres, in order to identify training needs. From this, nine teaching modules were developed and tested in pilot studies. These will be made freely available online. Second, we identified the need to disseminate, focus and increase awareness among teachers, design students and professionals for vulnerable generations. This was achieved through the establishment of an international design award. Three different categories of award with relevant sets of criteria were developed through an iterative process and have been launched and evaluated. The contribution of this paper is twofold. Firstly, to encourage educators, through the communication and dissemination of the results of the project, to extend their user groups to include design for vulnerable generations, and secondly to enhance designers’ interest and knowledge in working with design for vulnerable generations.
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| 4. |
- Malinverno, Matteo, et al.
(författare)
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Peg3/PW1 Is a Marker of a Subset of Vessel Associated Endothelial Progenitors
- 2017
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Ingår i: Stem Cells. - : WILEY. - 1066-5099 .- 1549-4918. ; 35:5, s. 1328-1340
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Tidskriftsartikel (refereegranskat)abstract
- Vascular associated endothelial cell (ECs) progenitors are still poorly studied and their role in the newly forming vasculature at embryonic or postnatal stage remains elusive. In the present work, we first defined a set of genes highly expressed during embryo development and strongly downregulated in the adult mouse. In this group, we then concentrated on the progenitor cell marker Peg3/PW1. By in vivo staining of the vasculature we found that only a subset of cells coexpressed endothelial markers and PW1. These cells were quite abundant in the embryo vasculature but declined in number at postnatal and adult stages. Using a reporter mouse for PW1 expression, we have been able to isolate PW1-positive (PW1posECs) and negative endothelial cells (PW1negECs). PW1-positive cells were highly proliferative in comparison to PW1negECs and were able to form colonies when seeded at clonal dilution. Furthermore, by RNAseq analysis, PW1posECs expressed endothelial cell markers together with mesenchymal and stem cell markers. When challenged by endothelial growth factors in vitro, PW1posECs were able to proliferate more than PW1negECs and to efficiently form new vessels in vivo. Taken together these data identify a subset of vessel associated endothelial cells with characteristics of progenitor cells. Considering their high proliferative potential these cells may be of particular importance to design therapies to improve the perfusion of ischemic tissues or to promote vascular repair.
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| 5. |
- Suinder, Christoph, et al.
(författare)
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Usability and Interoperability of IEC 61499 based distributed automation systems
- 2006
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Ingår i: 2006 IEEE International Conference on Industrial Informatics. - Piscataway, NJ : IEEE Communications Society. - 0780397002 ; , s. 31-37
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Konferensbidrag (refereegranskat)abstract
- Since IEC 61499 has reached the state of an international standard and a substantial body of research results exists the question of the authors as main intention for this paper was: Do the models of IEC 61499 solve all problems when thinking of usability and interoperability in heterogeneous system environments? The main problems discussed within the paper concern to the execution model defined for basic function blocks and the scheduling of events within function block networks
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| 6. |
- Sünder, Christoph, et al.
(författare)
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Usability and interoperability of IEC 61499 based distributed automation systems
- 2007
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Ingår i: 2006 4th IEEE International Conference on Industrial Informatics. - Piscataway, NJ : IEEE Communications Society. - 0780397010 - 0780397002 ; , s. 31-37
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Konferensbidrag (refereegranskat)abstract
- Since IEC 61499 has reached the state of an International Standard and a substantial body of research results exists the question of the authors as main intention for this paper was: Do the models of IEC 61499 solve all problems when thinking of usability and interoperability in heterogeneous system environments? The main problems discussed within the paper concern to the execution model defined for basic function blocks and the scheduling of events within function block networks
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