MHCII-independent CD4(+) T cells protect injured CNS neurons via IL-4

A body of experimental evidence suggests that T cells mediate neuroprotection following CNS injury; however, the antigen specificity of these T cells and how they mediate neuroprotection are unknown. Here, we have provided evidence that T cell-mediated neuroprotection after CNS injury can occur independently of major histocompatibility class II (MHCII) signaling to T cell receptors (TCRs). Using two murine models of CNS injury, we determined that damage-associated molecular mediators that originate from injured CNS tissue induce a population of neuroprotective, IL-4-producing T cells in an antigen-independent fashion. Compared with wild-type mice, IL-4-deficient animals had decreased functional recovery following CNS injury; however, transfer of CD4+ T cells from wild-type mice, but not from IL-4-deficient mice, enhanced neuronal survival. Using a culture-based system, we determined that T cell-derived IL-4 protects and induces recovery of injured neurons by activation of neuronal IL-4 receptors, which potentiated neurotrophin signaling via the AKT and MAPK pathways. Together, these findings demonstrate that damage-associated molecules from the injured CNS induce a neuroprotective T cell response that is independent of MHCII/TCR interactions and is MyD88 dependent. Moreover, our results indicate that IL-4 mediates neuroprotection and recovery of the injured CNS and suggest that strategies to enhance IL-4-producing CD4+ T cells have potential to attenuate axonal damage in the course of CNS injury in trauma, inflammation, or neurodegeneration

Rapid alterations of cell cycle control proteins in human T lymphocytes in microgravity

In our study we aimed to identify rapidly reacting gravity-responsive mechanisms in mammalian cells in order to understand if and how altered gravity is translated into a cellular response. In a combination of experiments using "functional weightlessness" provided by 2D-clinostats and real microgravity provided by several parabolic flight campaigns and compared to in-flight-1g-controls, we identified rapid gravity-responsive reactions inside the cell cycle regulatory machinery of human T lymphocytes. In response to 2D clinorotation, we detected an enhanced expression of p21 Waf1/Cip1 protein within minutes, less cdc25C protein expression and enhanced Ser147-phosphorylation of cyclinB1 after CD3/CD28 stimulation. Additionally, during 2D clinorotation, Tyr-15-phosphorylation occurred later and was shorter than in the 1 g controls. In CD3/CD28-stimulated primary human T cells, mRNA expression of the cell cycle arrest protein p21 increased 4.1-fold after 20s real microgravity in primary CD4+ T cells and 2.9-fold in Jurkat T cells, compared to 1 g in-flight controls after CD3/CD28 stimulation. The histone acetyltransferase (HAT) inhibitor curcumin was able to abrogate microgravity-induced p21 mRNA expression, whereas expression was enhanced by a histone deacetylase (HDAC) inhibitor. Therefore, we suppose that cell cycle progression in human T lymphocytes requires Earth gravity and that the disturbed expression of cell cycle regulatory proteins could contribute to the breakdown of the human immune system in space

Does feedback usage lead to electricity savings? Analysis of goals for usage, feedback seeking, and consumption behavior

Findings from smart metering trials throughout the European Union in the last 5 years suggest that feedback on electricity consumption does not result in the expected increase in electricity savings of 10%. Instead, a smaller reduction in electricity consumption between 1.5 and 4% is typically recorded. In this paper, we aim to analyze knowledge and motivation gained from feedback usage and the resulting effects on behavior. For this purpose, we introduce a theoretical framework describing the process of feedback use in the Rubicon model (Heckhausen and Gollwitzer in Motivation and Emotion, 11, 101–120, 1987) and the transition from gained knowledge into motivation, and subsequent adaptation of consumption behavior, by applying the Feedback Intervention Theory (FIT, Kluger and DeNisi in Psychological Bulletin, 119(2), 254–284, 1996). Using log-files on usage behavior of a web-based feedback system, survey data and energy consumption data from a 1-year trial of smart metering systems and feedback with more than 600 consumers, we identify six patterns distinguishing how users interact with feedback systems (i.e., measured by the quantity of log-ins and clicks for different features) and are able to make inferences on their knowledge gains. Moreover, we examine whether any feedback usage pattern could be related to a stronger agreement with any goals. Finally, we compare the impact of these different usage patterns onto energy consumption in order to uncover which knowledge gains could be associated with energy conservation. Results show that feedback usage can be differentiated along several specific seeking strategies which are associated with individual goals. The only strategy of feedback usage found to be successful for saving electricity is actually the one showing the least evidence for long-term knowledge being gained. Possible explanations for these findings are discussed within the context of assumptions for the FIT

Explaining regional acceptance of the German energy transition by including trust in stakeholders and perception of fairness as socio-institutional factors

In this paper we pursue the hypothesis that acceptance of the energy transition is not merely determined by technology acceptance but also by the perception of socio-institutional stakeholders and the perception of fairness. We test an acceptance model which includes the following main predictors: attitudes towards the risks of the energy transition and attitudes towards the technology options such as wind power, photovoltaic systems or transmission lines. Additional influences are assumed to arise from the perception of regional added values and the trust in various socio-institutional stakeholders. Furthermore, we expect fairness to be a mediating variable for acceptance. In this paper we test the model empirically with a representative German sample (N = 2009) in a structural equation model (SEM) for the acceptance of onshore wind power. Moreover, we analyse whether differences in the factors are related to the German regions North, East, West and South since we assume regional landscapes, renewable energy sources and socio-political contexts to be important for acceptance. Results show evidence that perception of stakeholders and fairness is important for the regional acceptance. In addition, results show that, among the four regions, different factors are relevant for acceptance. Results are discussed and conclusions for governance are drawn