Vascularity and perfusion of human gliomas xenografted in the athymic nude mouse.

The vascularisation and perfusion of seven subcutaneously xenografted human glioma lines established from surgical specimens has been analysed using an anti-collagen type IV antibody to visualise the vascular walls in combination with a perfusion marker (Hoechst 33342). A computer-based digital image processing system was employed for quantitative analysis of the parameters. The vascular architecture of individual tumours belonging to the same tumour line showed a consistent similarity, while substantial differences occurred between the various tumour lines derived from different patients. Despite the presence of a large inter-tumour variation in vascular area as a proportion of the tumour area, this vascular parameter clearly showed tumour line-specific characteristics. The perfused fraction of the tumour vessels also showed a large inter-tumour variation for all tumour lines ranging from 20% to 85%, but the majority of tumours of all lines had perfusion fractions of more than 55%. Despite large variation, the perfused vascular area as a proportion of the tumour cross-sectional area exhibited clear tumour line-specific tendencies. These observations suggest that consistent differences in vascular parameters are present between glioma xenograft lines, although the tumour lines all originated from histologically similar human high-grade gliomas. These differences may have important consequences for treatment and clinical behaviour of this type of tumour

Embryonal subregion-derived stromal cell lines from novel temperature-sensitive SV40 T antigen transgenic mice support hematopoiesis

Throughout life, the hematopoietic system requires a supportive microenvironment that allows for the maintenance and differentiation of hematopoietic stem cells (HSC). To understand the cellular interactions and molecules that provide these functions, investigators have previously established stromal cell lines from the late gestational stage and adult murine hematopoietic microenvironments. However, the stromal cell microenvironment that supports the emergence, expansion and maintenance of HSCs during mid-gestational stages has been largely unexplored. Since several tissues within the mouse embryo are known to harbor HSCs (i.e. aortagonads-mesonephros, yolk sac, liver), we generated numerous stromal cell clones from these mid-gestational sites. Owing to the limited cell numbers, isolations were performed with tissues from transgenic embryos containing the ts SV40 Tag gene (tsA58) under the transcriptional control of constitutive and ubiquitously expressing promoters. We report here that the growth and cloning efficiency of embryonic cells (with the exception of the aorta) is increased in the presence of the tsA58 transgene. Furthermore, our results show that the large panel of stromal clones isolated from the different embryonal subregions exhibit heterogeneity in their ability to promote murine and human hematopoietic differentiation. Despite our findings of heterogeneity in hematopoietic growth factor gene expression profiles, high-level expression of some factors may influence hematopoietic differentiation. Interestingly, a few of these stromal clones express a recently described chordin-like protein, which is an inhibitor of bone morphogenic proteins and is preferentially expressed in cells of the mesenchymal lineage

Games, Simulations, Immersive Environments, and Emerging Technologies

International audienceThis entry presents an overview of advanced technologies to support teaching and learning. The use of innovative interactive systems for education has never been higher. Far from being just a trend, the objective is to use the current technology to cover educational needs and create relevant pedagogical situations. The arguments in their favor are generally their positive effects on learners’ motivation and the necessity to provide learning methods adapted to our growing digital culture. The new learning technologies and emerging trends are first reviewed hereunder. We thus define and discuss learning games, gamification, simulation, immersive environments and other emerging technologies. Then, the current limits and remaining scientific challenges are highlighted

Games in Higher Education

International audienceThis entry presents an overview of how and why Learning Games are used in higher education.Learning Games can be defined as games that are designed to captivate the learners’ attention and facilitate their learning process. They have explicit educational purposes and can be used for teaching at all levels of education. All types of games can be used for learning: board games, card games, role-playing games, First Person Shooter games, simulation games, management games, puzzle games, treasure hunts…The main characteristic of Learning Games for higher education is the fact that they are designed to teach specific complex skills taught at university or during professional training programs. Unfortunately, it is not infrequent to observe strong opposition on the part of this target audience to this mode of learning, that these adult students associate with children.The use of Learning Games in primary school seems natural to teachers and is encouraged by specialists in didactics and neuroscience. This learning technique is much less frequently used in middle school and is almost completely absent from higher education. Yet teachers at all these levels are faced with the same problems, such as lack of motivation and investment, for which games are known to be an effective solution. This entry presents an overview of the games that can be used for higher education and the reasons why some teachers and students still show resistance to this type of learning. The numerous advantages of games for higher education will then be presented, citing games presently used in universities, in graduate schools and for professional training. Finally, thisDraft : Marfisi-Schottman I. (2019) Games in Higher Education. In: Tatnall A. (eds) Encyclopedia of Education and Information Technologies. Springer, Chamentry presents the current research questions that need to be addressed concerning the design of games for higher education and the acceptance of these games by teachers

Neuronal nitric oxide synthase contributes to the regulation of hematopoiesis

Nitric oxide (NO) signaling is important for the regulation of hematopoiesis. However, the role of individual NO synthase (NOS) isoforms is unclear. Our results indicate that the neuronal NOS isoform (nNOS) regulates hematopolesis in vitro and in vivo. nNOS is expressed in adult bone marrow and fetal liver and is enriched in stromal cells. There is a strong correlation between expression of nNOS in a panel of stromal cell lines established from bone marrow and fetal liver and the ability of these cell lines to support hematopoietic stem cells; furthermore, NO donor can further increase this ability. The number of colonies generated in vitro from the bone marrow and spleen of nNOS-null mutants is increased relative to wild-type or inducible- or endothelial NOS knockout mice. These results describe a new role for nNOS beyond its action in the brain and muscle and suggest a model where nNOS, expressed in stromal cells, produces NO which acts as a paracrine regulator of hematopoietic stem cells

Paclitaxel in self-micro emulsifying formulations: oral bioavailability study in mice

The anticancer drug paclitaxel is formulated for i.v. administration in a mixture of Cremophor EL and ethanol. Its oral bioavailability is very low due to the action of P-glycoprotein in the gut wall and CYP450 in gut wall and liver. However, proof-of-concept studies using the i.v. formulation diluted in drinking water have demonstrated the feasibility of the oral route as an alternative when given in combination with inhibitors of P-glycoprotein and CYP450. Because of the unacceptable pharmaceutical properties of the drinking solution, a better formulation for oral application is needed. We have evaluated the suitability of various self-micro emulsifying oily formulations (SMEOF’s) of paclitaxel for oral application using wild-type and P-glycoprotein knockout mice and cyclosporin A (CsA) as P-glycoprotein and CYP450 inhibitor. The oral bioavailability of paclitaxel in all SMEOF’s without concomitant CsA was low in wild-type mice, showing that this vehicle does not enhance intestinal uptake by itself. Paclitaxel (10 mg/kg) in SMEOF#3 given with CsA resulted in plasma levels that were comparable to the Cremophor EL-ethanol containing drinking solution plus CsA. Whereas the AUC increased linearly with the oral paclitaxel dose in P-glycoprotein knockout mice, it increased less than proportional in wild-type mice given with CsA. In both strains more unchanged paclitaxel was recovered in the feces at higher doses. This observation most likely reflects more profound precipitation of paclitaxel within the gastro-intestinal tract at higher doses. The resulting absolute reduction in absorption of paclitaxel from the gut was possibly concealed by partial saturation of first-pass metabolism when P-glycoprotein was absent. In conclusion, SMEOF’s maybe a useful vehicle for oral delivery of paclitaxel in combination with CsA, although the physical stability within the gastro-intestinal tract remains a critical issue, especially when applied at higher dose levels