Pyrogene Wirkung von mycoplasmalen Lipopeptiden und bakteriellem Endotoxin bei Toll like Rezeptor-2-defizienten Mäusen und bei CD36-defizienten spontan hypertensiven Ratten

Das Makrophagen-aktivierende Lipopeptid-2 (MALP-2) von Mycoplasma fermentans und das Fibroblasten-stimulierende Lipopeptid-1 (FSL-1) von Mycoplasma salivarium scheinen durch die Aktivierung der Toll-like Rezeptoren (TLRs) 2 und 6 die angeborene Immunantwort zu induzieren. CD36 gilt als zellulärer Sensor für diacylierte Lipopeptide wie MALP-2 und FSL-1 und könnte für die durch solche Lipopeptide ausgelösten Effekte in vivo erforderlich sein. Aus diesem Grund wurden in dieser Studie die Ansprechbarkeit von TLR2- ko-Mäusen (TLR2-ko), ihrer Wildtyp-Mäuse (C57/BL-6) sowie die von CD36-defizienten spontan hypertensiven Ratten (SHR) und ihren genetischen Kontrollen, den Wistar Kyoto Ratten (WKY), auf die systemische Stimulation mit TLR2/6-Agonisten MALP-2 und FSL-1 sowie mit dem TLR4-Agonisten Lipopolysaccharid (LPS) untersucht. Hierzu wurde den verwendeten Mäusen und Ratten ein Radiotransmitter intraabdominal implantiert, der die Körpertemperatur und die motorische Aktivität aufzeichnete. Um weitere charakteristische Merkmale des „sickness behaviors“ überprüfen zu können, wurde bei den Ratten zusätzlich die Futter- und Wasseraufnahme gemessen, um die Entwicklung von Anorexie und Adipsie ermitteln zu können. Des weiteren wurden bei den Ratten und Mäusen die im Blut zirkulierenden Tumor Nekrose Faktor (TNF)- und Interleukin-6 (IL-6)-Gehalte mit Hilfe von Bioassays ermittelt. Die inflammatorische Aktivierung des Gehirns wurde über die Quantifizierung der nukleären Translokation des Transkriptionsfaktors STAT3 (signal transducer and activator of transcription 3) in fieber- und sickness behavior-relevanten Gehirnstrukturen überprüft. Bei den TLR2-ko-Mäusen fiel die Fieberantwort sowie die Bildung der beiden Zytokine IL-6 und TNF nach intraperitonealer Stimulation mit MALP-2 und FSL-1 im Vergleich zu den Kontrolltieren komplett aus, wohingegen die Reaktivität der Ko-Mäuse nach intaperitonealer Injektion von LPS im Vergleich zu den Wildtyp-Mäusen unbeeinträchtigt blieb. Die CD36 defizienten SHR zeigten nach MALP-Stimulation eine Abschwächung der Fieberantwort und des sickness behaviors, diese Reduktion der Responsivität fiel jedoch nach LPS-Stimulation im Vergleich zu den WKY noch stärker aus. Die zirkulierenden Zytokine sowie die Anzahl der STAT3-Signale in den relevanten Gehirnstrukturen waren allerdings bei SHR wie WKY nach Stimulation beider Pyrogene weitgehend identisch, was zeigt, dass die inflammatorische Aktivierung des Gehirns als Antwort auf die MALP-2-, FSL-1 und LPSStimulation durch die CD36-Defizienz nicht beeinträchtigt wird. Diese Ergebnisse demonstrieren eindeutig, dass der TLR2 für die Manifestation der MALP-2- und FSL-1-induzierten, nicht aber für die LPS-induzierten inflammatorischen Antworten essentiell ist. Eine geringgradige Beteiligung des CD36-Rezeptors an der MALP- 2-induzierten Krankheits- und Zytokinantwort ist nicht auszuschließen, aber eher unwahrscheinlich, da die LPS-Antwort bei SHR ebenfalls verringert war. Die beobachtete Reduktion des MALP-2- und LPS-induzierten Fiebers rührt wahrscheinlich eher von weiteren endokrinen Abnormalitäten der SHR her, die bei diesen Tieren stärkere antipyretische Kapazitäten bewirken.Macrophage-activating lipopeptide-2 (MALP-2) from Mycoplasma fermentans and fibroblast- stimulating Lipopeptid-1 from Mycoplasma salivarium seem to induce an innate immune response via activation of Toll-like receptors (TLRs) 2 and 6. CD36 is regarded as a cellular sensor of diacylated lipopeptides such as MALP-2 or FSL-1 and may be required for the array of MALP-2/FSL-1-induced effects in vivo. We therefore tested the responses of TLR2-knockout mice (TLR2-ko) and wildly mice (C57/Bl-6), and of CD36 deficient spontaneously hypertensive rats (SHR) and their genetic controls (Wister Kyoto rats, WKY) to systemic stimulations with the TLR2/6 agonists MALP-2 and FSL-1 and the TLR4 agonist lip polysaccharide (LPS). TRL2-ko, C57/BL-6, SHR and WKY were intraabdominally implanted with radiotransmitters for recording of body temperature (fever) and motor activity. Food and water intake were also measured to determine a possible development of anorexia and adipsia as characteristic components of brain-controlled sickness responses. Circulating levels of tumor necrosis factor (TNF) and inteleukin-6 (IL-6) were measured by use of specific bioassays. Inflammatory activation of the brain was determined by quantification of a nuclear translocation of the transcription factor STAT3 (signal transducer and activator of transcription 3) in brain areas, relevant for the manifestation of fever and sickness behaviour. Fever and formation of TNF and IL-6 induced by intraperitoneal injections of MALP-2 and FSL-1 were completely blunted in TLR2-ko mice, while LPS-induced responses were not impaired in these animals when compared to those of C57/BL-6 wildtyp mice. In SHR lacking CD36 an attenuation of fever and sickness behaviour was observed in response to MALP-2, but even to a higher degree in response to LPS, when compared to WKY controls. Circulating cytokines and numbers of nuclear STAT3 signals in relevant areas of the brain were identical in SHR and WKY after stimulation with both pyrogens, indicating that the inflammatory activation of the brain in response to MALP-2 (and LPS) is not impaired by the lack of CD36. These results demonstrate unequivocally that TLR2 is essential for the manifestation of MALP-2/FSL-1-induced (but not for LPS-induced) inflammatory responses. A moderate participation of CD36 in MALP-2-induced sickness- and cytokine-responses can not be ruled out, but is rather unlikely since LPS-induced inflammatory responses were also attenuated in SHR. The observed attenuations in MALP-2 and LPS-induced fever in SHR may rather be caused by some of the endocrine abnormalities in these rats resulting in stronger endogenous antipyretic capacities

Mobility management at district level - The impact of car-reduced districts on mobility behaviour

The model district Freiburg-Vauban is one of the first low-car housing projects in Germany. Within the project "Optimisation of the Traffic Concept of the District Freiburg-Vauban during Implementation" sponsored by the German Federal Foundation for Environment, an evaluation of the traffic concept was carried out. The Analysis described in this paper is part of the project and edlivers data in a new scientific quality about the way in which thes kind of car-reduction measures influence mobility behaviour

Enhancing the Effectiveness of Travel Awareness Campaigns Via the Inclusion of Theoretical - Based Content

Travel awareness campaigns are one of the most commonly used ‘mobility management interventions’, which aim to change individuals’ travel choices and behaviour to more sustainable transport modes. However, despite the widespread uptake of this measure and associated costs, the extent to which awareness campaigns work, and also how they can be best designed to increase their effectiveness, remains unclear. We begin by providing an overview of current understanding of individuals’ modal choice decision making processes, and how this knowledge can be applied to the design of awareness campaigns. To illustrate the benefits of including psychological-based content in the design of travel awareness messaging, an overview of a theoretical-based randomised controlled personalised travel planning intervention study conducted in Hammersmith, UK, is presented. The results obtained show that those people who were exposed to theoretical-based materials reported a significantly greater change in behaviour and theoretical stage-movement, compared to those who received non-theoretical materials and also the control group. Based on the results of this study, we conclude by suggesting how future awareness campaigns can be improved via the inclusion of theoretical-based content

First steps towards cross-national transfer in integrating mobility management and land use planning in the EU and Switzerland

This paper is based on research carried out in an EU Framework project, concerning the better integration of mobility management (MM) with land use planning. The objective of the paper is to analyse how, and how far, policies in this field of action can transfer from one member state to another, and to compare this to the theory of policy transfer put forward by Dolowitz and Marsh (2000), using their theory as an analytical framework, but also informing that theory. After providing a definition of this form of integration, the paper explains how far MM and land use planning are currently integrated in the EU member and other states covered in the research (Sweden, Germany, Spain, Lithuania, Poland, Slovenia, Switzerland, the UK, as well as Ireland and the Netherlands). It then presents the results of planning simulation workshops in five of these countries, where a group of planning professionals from each state considered real development sites and how MM could be integrated with the development. It shows that there is scope for transfer but concludes that barriers such as language, differing planning traditions, and the problem of transferring a new policy idea within a country will limit the scope of policy transfer significantly. Nonetheless, it sees a role for EU projects of this nature in encouraging initial consideration of new policy ideas.Research highlights► Integration of mobility management and planning as an example of policy transfer. ► Case studies of 5 planning simulation workshops across Europe. ► Major barriers to transfer exist: legal, cultural, and awareness. ► Policy transfer within a country is as important as transfer between countries. ► EU projects can begin process of policy transfe

Residential housing prices: impact of housing characteristics, accessibility and neighbouring apartments – a case study of Dortmund, Germany

In this research we analyse the most important factors that determine housing prices. On the one hand, we test whether neighbourhoods with a good accessibility are more attractive and consequently show higher housing prices. For this purpose, we introduce an adapted Walk Score as part of the accessibility indicators. On the other hand, we compare an ordinary-least-squares regression (OLS) and a spatial lag model and test which model better explains residential housing prices. The regression models show the importance of classical factors such as dwelling characteristics or the types of neighbours. In addition, they also reveal that a differentiated approach is needed for analysing the accessibility, the location and the environment of a dwelling. The mere presence of a single amenity, a public transport stop or a motorway access is not a sufficient explanatory factor. Information such as density of supply, walking distances or public transport service quality needs to be taken into account as well as. The test of the spatial lag model reveals that prices of the most proximate dwellings can be taken into account as a relevant factor in explaining residential housing prices and should therefore be included in research on residential housing prices

First steps towards cross-national transfer in integrating mobility management and land use planning in the EU and Switzerland

This paper is based on research carried out in an EU Framework project, concerning the better integration of mobility management (MM) with land use planning. The objective of the paper is to analyse how, and how far, policies in this field of action can transfer from one member state to another, and to compare this to the theory of policy transfer put forward by Dolowitz and Marsh (2000), using their theory as an analytical framework, but also informing that theory. After providing a definition of this form of integration, the paper explains how far MM and land use planning are currently integrated in the EU member and other states covered in the research (Sweden, Germany, Spain, Lithuania, Poland, Slovenia, Switzerland, the UK, as well as Ireland and the Netherlands). It then presents the results of planning simulation workshops in five of these countries, where a group of planning professionals from each state considered real development sites and how MM could be integrated with the development. It shows that there is scope for transfer but concludes that barriers such as language, differing planning traditions, and the problem of transferring a new policy idea within a country will limit the scope of policy transfer significantly. Nonetheless, it sees a role for EU projects of this nature in encouraging initial consideration of new policy ideas.Mobility management Land use planning Integration Policy transfer

Determinants and effects of perceived walkability: a literature review, conceptual model and research agenda

For decades, accessibility – i.e. the ease of reaching destinations – has been an important concept in transport planning, resulting in many studies trying to measure it and put it into practice. Also walkability, a mode-specific type of accessibility referring to how easy it is to walk (to destinations) received increased attention in the last two decades. In recent years, a new focus has been on how people perceive their accessibility as this may be a stronger predictor of travel behaviour than objective elements of accessibility (such as built environment characteristics). Perceived walkability, i.e. how walk-friendly people experience a certain area, however, has only been explored by a limited number of studies. In this review paper, we give an overview of existing studies analysing perceived walkability, which mostly have focused on its effects on walking frequency/duration, physical activity and various aspects of mental well-being. Based on this literature review, a conceptual model is created, emphasising the determinants and effects of perceived walkability and how it is related to objective walkability. We end this paper by providing avenues for further research, including the introduction of a Short Perceived Walkability Scale (SPWS) and recommendations for data collection and analysis. Doing so can create new insights into perceived walkability and links with related elements, and therefore can contribute to stimulating walking trips and improving the experience of these trips