Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Trypanosoma cruzi Infection

Arginase-1 (Arg-1) is a marker for alternatively activated macrophages (AAM) and is mainly induced by the type 2 cytokines interleukin (IL)-4 and IL-13 through the common IL-4 receptor-alpha (Rα) subunit. Both, Arg-1 and AAM undermine macrophage effector functions against intracellular parasites and are therefore implicated in the susceptibility to infection with Trypanosoma cruzi, the causative agent of Chagas' disease. However, the involvement of Arg-1 in promoting intracellular replication of T. cruzi in AAM has not been proven so far in vivo. Because Arg-1 is only moderately expressed in T. cruzi-infected wildtype mice, we elucidated the role of Arg-1 and AAM during infection in IL-13-overexpressing (IL-13tg) mice, which are characterized by an inflammation-induced development of AAM and an accompanied elevated expression of Arg-1. In comparison to wildtype littermates, IL-13tg mice were highly susceptible to T. cruzi infection with enhanced parasitemia and impaired survival. Importantly, T. cruzi-infected IL-13tg mice developed an elevated alternative macrophage activation with increased arginase activity. To proof the hypothesis, that Arg-1 accounts for the increased susceptibility of IL-13tg mice, we blocked arginase activity in infected IL-13tg mice. Because this arginase inhibition resulted in a decreased susceptibility to experimental Chagas disease our study supports in summary the conclusion that IL-13/IL-4Rα-driven Arg-1 expression contributes to the permissiveness of the host to T. cruzi infection

ÖR-Klausurbearbeitung: Grundlagenwissen rund um den Bebauungsplan

Sowohl im ersten als auch im zweiten Examen werden Klausuren rund um den Bebauungsplan gestellt. Oft sind Prüflinge dazu aufgerufen, eine Satzung auf formelle und materielle Fehler zu untersuchen und die richtigen Schlüsse aus den gefundenen Fehlern zu ziehen. Im vorliegenden Beitrag stellen wir die formellen und materiellen Rechtmäßigkeitsvoraussetzungen eines Bebauungsplans dar (I.) und erörtern die Folgen von Rechtsfehlern (II.). Wer sich zusätzlich für einen alternativen Lernansatz interessiert, um einen Überblick über die für die Rechtmäßigkeitsprüfung relevanten Normen zu erlangen, kann einen Blick auf die ebenfalls in diesem Heft abgedruckte Merkhilfe werfen

Discursive design thinking: the role of explicit knowledge in creative architectural design reasoning

The main hypothesis investigated in this paper is based upon the suggestion that the discursive reasoning in architecture supported by an explicit knowledge of spatial configurations can enhance both design productivity and the intelligibility of design solutions. The study consists of an examination of an architect’s performance while solving intuitively a well-defined problem followed by an analysis of the spatial structure of their design solutions. One group of architects will attempt to solve the design problem logically, rationalizing their design decisions by implementing their explicit knowledge of spatial configurations. The other group will use an implicit form of such knowledge arising from their architectural education to reason about their design acts. An integrated model of protocol analysis combining linkography and macroscopic coding is used to analyze the design processes. The resulting design outcomes will be evaluated quantitatively in terms of their spatial configurations. The analysis appears to show that an explicit knowledge of the rules of spatial configurations, as possessed by the first group of architects can partially enhance their function-driven judgment producing permeable and well-structured spaces. These findings are particularly significant as they imply that an explicit rather than an implicit knowledge of the fundamental rules that make a layout possible can lead to a considerable improvement in both the design process and product. This suggests that by externalizing th

Motivation moderates gender differences in navigation performance.

Gender differences in navigation performance are a recurrent and controversial topic. Previous research suggests that men outperform women in navigation tasks and that men and women exhibit different navigation strategies. Here, we investigate whether motivation to complete the task moderates the relationship between navigation performance and gender. Participants learned the locations of landmarks in a novel virtual city. During learning, participants could trigger a top-down map that depicted their current position and the locations of the landmarks. During testing, participants were divided into control and treatment groups and were not allowed to consult the map. All participants were given 16 minutes to navigate to the landmarks, but those in the treatment group were monetarily penalized for every second they spent completing the task. Results revealed a negative relationship between physiological arousal and the time required to locate the landmarks. In addition, gender differences in strategy were found during learning, with women spending more time with the map and taking 40% longer than men to locate the landmarks. Interestingly, an interaction between gender and treatment group revealed that women in the control group required more time than men and women in the treatment group to retrieve the landmarks. During testing, women in the control group also took more circuitous routes compared to men in the control group and women in the treatment group. These results suggest that a concurrent and relevant stressor can motivate women to perform similarly to men, helping to diminish pervasive gender differences found in the navigation literature

Archetyping shared socioeconomic pathways across scales: an application to central Asia and European case studies

The complex interactions of drivers represented in scenarios and climate change impacts across scales have led to the development of multiscale scenarios. Since the recent development of global shared socioeconomic pathways (SSPs), which have started being downscaled to lower scales, the potential of scenarios to be relevant for decision making and facilitate appreciation and inclusion of different perspectives has been increasing, compared with a single-scale global scenario set. However, in practice, quantitative downscaling of global scenarios results in narratives that are compressed from the global level to fit the local context to enhance consistency between global and local scales. We brought forward the concept of scenario archetypes to analyze multiscale SSP scenario narratives and highlight important diverging assumptions within the same archetype. Our methodology applied scenario archetypes both as typologies, to allocate specific cases of scenarios into existing scenario archetypes, and building blocks, conceptualized with worldviews from cultural theory. Although global SSPs generally match existing archetypes and tend to be well defined, the socially unequal SSPs at subglobal scales are more nuanced, and dominant worldviews are much less straighforward to interpret than in global scenarios. The closest match was the great transition–sustainability (SSP1) archetype, whereas the most divergent was the market forces–fossil fuel development (SSP5) archetype. Overall, our results highlight the need to improve uptake of bottom-up approaches in global scenarios to improve appreciation of different perspectives as sought after in multiscale scenarios

Exploring Individual Differences and Building Complexity in Wayfinding:The Case of the Seattle Central Library

This article focuses on the interactions between individual differences and building characteristics that may occur during multilevel wayfinding. Using the Seattle Central Library as our test case, we defined a series of within-floor and between-floor wayfinding tasks based on different building analyses of this uniquely designed structure. Tracking our 59 participants while they completed assigned tasks on-site, we examined their wayfinding performance across tasks and in relation to a variety of individual differences measures and wayfinding strategies. Both individual differences and spatial configuration, as well as the organization of the physical space, were related to the wayfinding challenges inherent to this library. We also found wayfinding differences based on other, nonspatial features, such as semantic expectations about destinations. Together, these results indicate that researchers and building planners must consider the interactions among building, human, and task characteristics in a more nuanced fashion