The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis

Citizen science’s transformative impact on science, citizen empowerment and socio-political processes

Citizen science (CS) can foster transformative impact for science, citizen empowerment and socio-political processes. To unleash this impact, a clearer understanding of its current status and challenges for its development is needed. Using quantitative indicators developed in a collaborative stakeholder process, our study provides a comprehensive overview of the current status of CS in Germany, Austria and Switzerland. Our online survey with 340 responses focused on CS impact through (1) scientific practices, (2) participant learning and empowerment, and (3) socio-political processes. With regard to scientific impact, we found that data quality control is an established component of CS practice, while publication of CS data and results has not yet been achieved by all project coordinators (55%). Key benefits for citizen scientists were the experience of collective impact (“making a difference together with others”) as well as gaining new knowledge. For the citizen scientists’ learning outcomes, different forms of social learning, such as systematic feedback or personal mentoring, were essential. While the majority of respondents attributed an important value to CS for decision-making, only few were confident that CS data were indeed utilized as evidence by decision-makers. Based on these results, we recommend (1) that project coordinators and researchers strengthen scientific impact by fostering data management and publications, (2) that project coordinators and citizen scientists enhance participant impact by promoting social learning opportunities and (3) that project initiators and CS networks foster socio-political impact through early engagement with decision-makers and alignment with ongoing policy processes. In this way, CS can evolve its transformative impact

The neural correlates of generative reasoning in subclinical depression

In this research, we plan to study the processes underlying the cognitive deficits in sad mood and subclinical depression, in order to further understand this pervasive problem. Subclinical depression and lasting states of sad mood are characterized by impairments in flexible, creative reasoning, and in "generative thinking" which means the construction of impressions, plans, and mental models out of more basic, detail information. Using brain imaging, we aim to investigate the idea of a highly specific deficit in depressed mood. Those brain areas that are known to be associated with generative thinking should be activated if someone uses this type of reasoning when learning a new set of information. If, as proposed, those with subclinical depression are not generating a mental model during learning, then this pattern of brain activation may not be seen until queried later about the learned information, reflecting a less accurate on-line reasoning strategy. A comparison between subclinically depressed versus nondepressed participants will thus provide a more direct insight into the cognitive strategies employed by participants in the two different groups. The findings may also help to improve the goal-setting for counselling and intervention programs directed at those with long-lasting sad mood

Spatial representation of coherence

Four experiments examined spatial correlates of the experience of coherence, that is, the extent to which propositions ‘fit together’. Experiment 1 demonstrates for Heiderian triads (i.e., sets of liking/disliking relations between three fictitious persons) that name pairs from balanced triads, such as two friends commonly disliking a third person (high coherence) are seen as closer to each other in physical space as compared to name pairs from unbalanced triads, such as two persons disliking each other and having a common friend (low coherence). This pattern of results is conceptually replicated in two further experiments for categorical syllogisms. Two terms in conclusions from valid syllogisms (high coherence) were seen as spatially closer to each other than when two terms came from invalid syllogisms (low coherence). In the final two experiments, similar closeness effects are demonstrated for word pairs from scenarios that “made sense” in terms of causal connectedness (latent causality) as opposed to word pairs from scenarios perceived as causally unconnected. These findings are discussed in the context of spatial binding theories, applied psychology, and embodied cognition in general, and their methodological implications are highlighted