Immune clearance of attenuated rabies virus results in neuronal survival with altered gene expression.

Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, to the absence of a permanent mark on once-infected cells that allow their identification long after viral clearance. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre) to switch neurons constitutively expressing tdTomato (red) to expression of a Cre-inducible EGFP (green), permanently marking neurons that had been infected in vivo. We used fluorescence microscopy and quantitative real-time PCR to measure the survival of neurons after viral clearance; we found that the vast majority of RABV-infected neurons survive both infection and immunological clearance. We were able to isolate these previously infected neurons by flow cytometry and assay their gene expression profiles compared to uninfected cells. We observed transcriptional changes in these cured neurons, predictive of decreased neurite growth and dysregulated microtubule dynamics. This suggests that viral clearance, though allowing for survival of neurons, may not restore them to their pre-infection functionality. Our data provide a proof-of-principle foundation to re-evaluate the etiology of human central nervous system diseases of unknown etiology: viruses may trigger permanent neuronal damage that can persist or progress in the absence of sustained viral antigen

Planning Multifunctional Green Infrastructure in Urban Areas - Advanced Approaches Based on Case Studies from Denmark, Germany and the UK

Green infrastructure (GI) is considered to be a planning concept that has potential to improve green space planning in urban areas by offering a holistic, integrated approach (e.g., Pauleit et al., 2011; Davies et al., 2015). In this paper we focus on multifunctionality as an important principle of GI planning. By scrutinizing case studies in Germany (Berlin), the UK (Edinburgh), and Denmark (Aarhus), we examine how multifunctionality is acknowledged by urban green space practitioners and provide recommendations on how to consider multifunctionality more proactively and comprehensively

Key insights for the future of urban ecosystem services research

Understanding the dynamics of urban ecosystem services is a necessary requirement for adequate planning, management, and governance of urban green infrastructure. Through the three-year Urban Biodiversity and Ecosystem Services (URBES) research project, we conducted case study and comparative research on urban biodiversity and ecosystem services across seven cities in Europe and the United States. Reviewing > 50 peer-reviewed publications from the project, we present and discuss seven key insights that reflect cumulative findings from the project as well as the state-of-the-art knowledge in urban ecosystem services research. The insights from our review indicate that cross-sectoral, multiscale, interdisciplinary research is beginning to provide a solid scientific foundation for applying the ecosystem services framework in urban areas and land management. Our review offers a foundation for seeking novel, nature-based solutions to emerging urban challenges such as wicked environmental change issues

The uptake of the ecosystem services concept in planning discourses of European and American cities

Ecosystem services (ES) are gaining increasing attention as a promising concept to more actively consider and plan for the varied benefits of the urban environment. Yet, to have an impact on decision-making, the concept must spread from academia to practice. To understand how ES have been taken up in planning discourses we conducted a cross-case comparison of planning documents in Berlin, New York, Salzburg, Seattle and Stockholm. We found: (1) explicit references to the ES concept were primarily in documents from Stockholm and New York, two cities in countries that entered into ES discourses early. (2) Implicit references and thus potential linkages between the ES concept and planning discourses were found frequently among all cities, especially in Seattle. (3) The thematic scope, represented by 21 different ES, is comparably broad among the cases, while cultural services and habitat provision are most frequently emphasized. (4) High-level policies were shown to promote the adoption of the ES concept in planning. We find that the ES concept holds potential to strengthen a holistic consideration of urban nature and its benefits in planning. We also revealed potential for further development of ES approaches with regard to mitigation of environmental impacts and improving urban resilience