Exposure to TARC alters beta2-adrenergic receptor signaling in human peripheral blood T lymphocytes

The beta(2)-adrenergic receptor (beta(2)-AR) negatively regulates T cell activity through the activation of the G(s)/adenylyl cyclase/cAMP pathway. beta(2)-AR desensitization, which can be induced by its phosphorylation, may have important consequences for the regulation of T cell function in asthma. In the present study we demonstrate that the C-C chemokine thymus and activation-regulated chemokine (TARC) impairs the ability of beta(2)-agonist fenoterol to activate the cAMP downstream effector cAMP-responsive element binding protein (CREB) in freshly isolated human T cells. The TARC-induced activation of Src kinases resulted in membrane translocation of both G protein-coupled receptor kinase (GRK) 2 and beta-arrestin. Moreover, TARC was able to induce Src-dependent serine phosphorylation of the beta(2)-AR as well as its association with GRK2 and beta-arrestin. Finally, in contrast to CREB, phosphorylation of Src and extracellular signal-regulated kinase was enhanced by fenoterol upon TARC pretreatment. In summary, we show for the first time that TARC exposure impairs beta(2)-AR function in T cells. Our data suggest that this is mediated by Src-dependent activation of GRK2, resulting in receptor phosphorylation, binding to beta-arrestin, and a switch from cAMP-dependent signaling to activation of the MAPK pathway. We propose that aberrant T cell control in the presence of endogenous beta-agonists promotes T cell-mediated inflammation in asthma

Quantum dots for multimodal molecular imaging of angiogenesis

Quantum dots exhibit unique optical properties for bioimaging purposes. We have previously developed quantum dots with a paramagnetic and functionalized coating and have shown their potential for molecular imaging purposes. In the current mini-review we summarize the synthesis procedure, the in vitro testing and, importantly, the in vivo application for multimodal molecular imaging of tumor angiogenesis

The effects of the number of links and navigation support on cognitive load and learning with hypertext: The mediating role of reading order

In an experiment, we tested DeStefano and LeFevre's predictions as well as the usefulness of link suggestions. Participants used different versions of a hypertext, either with 3-links or 8-links per page, presenting link suggestions or not. We tested their cognitive load and learning outcomes. Results showed that there was a benefit of using link suggestions for learning, but no effect of number of links on learning was found. Moreover, the effects of our manipulations on cognitive load were mediated by the reading order that participants selected. Implications for research and the design of navigation support systems are discussed

Distinct Stromal Cell Factor Combinations Can Separately Control Hematopoietic Stem Cell Survival, Proliferation, and Self-Renewal

SummaryHematopoietic stem cells (HSCs) are identified by their ability to sustain prolonged blood cell production in vivo, although recent evidence suggests that durable self-renewal (DSR) is shared by HSC subtypes with distinct self-perpetuating differentiation programs. Net expansions of DSR-HSCs occur in vivo, but molecularly defined conditions that support similar responses in vitro are lacking. We hypothesized that this might require a combination of factors that differentially promote HSC viability, proliferation, and self-renewal. We now demonstrate that HSC survival and maintenance of DSR potential are variably supported by different Steel factor (SF)-containing cocktails with similar HSC-mitogenic activities. In addition, stromal cells produce other factors, including nerve growth factor and collagen 1, that can antagonize the apoptosis of initially quiescent adult HSCs and, in combination with SF and interleukin-11, produce >15-fold net expansions of DSR-HSCs ex vivo within 7 days. These findings point to the molecular basis of HSC control and expansion

Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm

This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson’s correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49–0.59] for epicardial activation, 0.50 ± 0.27 [0.41–0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32–0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9–29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification

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

Influence of head models on neuromagnetic fields and inverse source localizations

BACKGROUND: The magnetoencephalograms (MEGs) are mainly due to the source currents. However, there is a significant contribution to MEGs from the volume currents. The structure of the anatomical surfaces, e.g., gray and white matter, could severely influence the flow of volume currents in a head model. This, in turn, will also influence the MEGs and the inverse source localizations. This was examined in detail with three different human head models. METHODS: Three finite element head models constructed from segmented MR images of an adult male subject were used for this study. These models were: (1) Model 1: full model with eleven tissues that included detailed structure of the scalp, hard and soft skull bone, CSF, gray and white matter and other prominent tissues, (2) the Model 2 was derived from the Model 1 in which the conductivity of gray matter was set equal to the white matter, i.e., a ten tissuetype model, (3) the Model 3 consisted of scalp, hard skull bone, CSF, gray and white matter, i.e., a five tissue-type model. The lead fields and MEGs due to dipolar sources in the motor cortex were computed for all three models. The dipolar sources were oriented normal to the cortical surface and had a dipole moment of 100 μA meter. The inverse source localizations were performed with an exhaustive search pattern in the motor cortex area. A set of 100 trial inverse runs was made covering the 3 cm cube motor cortex area in a random fashion. The Model 1 was used as a reference model. RESULTS: The reference model (Model 1), as expected, performed best in localizing the sources in the motor cortex area. The Model 3 performed the worst. The mean source localization errors (MLEs) of the Model 3 were larger than the Model 1 or 2. The contour plots of the magnetic fields on top of the head were also different for all three models. The magnetic fields due to source currents were larger in magnitude as compared to the magnetic fields of volume currents. DISCUSSION: These results indicate that the complexity of head models strongly influences the MEGs and the inverse source localizations. A more complex head model performs better in inverse source localizations as compared to a model with lesser tissue surfaces

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