Sense and Immunity: Context-Dependent Neuro-Immune Interplay

The sensory nervous and immune systems, historically considered autonomous, actually work in concert to promote host defense and tissue homeostasis. These systems interact with each other through a common language of cell surface G protein-coupled receptors and receptor tyrosine kinases as well as cytokines, growth factors, and neuropeptides. While this bidirectional communication is adaptive in many settings, helping protect from danger, it can also become maladaptive and contribute to disease pathophysiology. The fundamental logic of how, where, and when sensory neurons and immune cells contribute to either health or disease remains, however, unclear. Our lab and others’ have begun to explore how this neuro-immune reciprocal dialog contributes to physiological and pathological immune responses and sensory disorders. The cumulative results collected so far indicate that there is an important role for nociceptors (noxious stimulus detecting sensory neurons) in driving immune responses, but that this is highly context dependent. To illustrate this concept, we present our findings in a model of airway inflammation, in which nociceptors seem to have major involvement in type 2 but not type 1 adaptive immunity

Random planar graphs and the London street network

In this paper we analyse the street network of London both in its primary and dual representation. To understand its properties, we consider three idealised models based on a grid, a static random planar graph and a growing random planar graph. Comparing the models and the street network, we find that the streets of London form a self-organising system whose growth is characterised by a strict interaction between the metrical and informational space. In particular, a principle of least effort appears to create a balance between the physical and the mental effort required to navigate the city

Looking backward, looking forward: the city region of the mid-21st century

Emerging as a serious tool of analysis in the United States around 1950, the city region concept was increasingly applied in a European context after 1980. Since 2000, it has evolved further with recognition of the polycentric mega-city region, first recognised in Eastern Asia but now seen as an emerging urban form both in Europe and the United States. The paper speculates on the main changes that may impact on the growth and development of such complex urban regions in the first half of the 21st century, concluding that achieving the goal of polycentric urban development may prove more complex than at first it may seem

Reflections on the innovative city : examining three innovative locations in a knowledge bases framework

Abstract This paper combines three location-based cases with literature background focusing on knowledge bases and cities. The paper considers the regional context of the city of Helsinki and its surrounding area (HMA). Analyzed cases include three specific locations highlighting urban form, connectivity and knowledge-intensive production. Conceptually innovative cities are experiencing extensive change as they transform and change in order to become competitive providers of first class living for highly skilled global work-force. The integration of spatial characteristics into analyses of knowledge intensiveness of cities brings forth new theoretical openings for urban analysis setting platforms for open innovation and economy. The paper focuses on extensive material resources collected in numerous projects. The data gives more reliable picture of the knowledge-intensive locations compared to single interviews or survey studies. The total data includes work and education statistics, stakeholder interviews and observation field work. Provided reflections are classified according to key issues presented in urban studies and economic geography

Kinetics of the hydrogen abstraction ·C2H5 + alkane → C2H6 + alkyl reaction class: an application of the reaction class transition state theory

This paper presents an application of the reaction class transition state theory (RC-TST) to predict thermal rate constants for hydrogen abstraction reactions at alkane by the C2H5 radical on-the-fly. The linear energy relationship (LER), developed for acyclic alkanes, was also proven to hold for cyclic alkanes. We have derived all RCTST parameters from rate constants of 19 representative reactions, coupling with LER and the barrier height grouping (BHG) approach. Both the RC-TST/LER, where only reaction energy is needed, and the RC-TST/BHG, where no other information is needed, can predict rate constants for any reaction in this reaction class with satisfactory accuracy for combustion modeling. Our analysis indicates that less than 50% systematic errors on the average exist in the predicted rate constants using either the RC-TST/LER or RC-TST/BHG method, while in comparison with explicit rate calculations, the differences are within a factor of 2 on the average. The results also show that the RC-TST method is not sensitive to the choice of density functional theory used

Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma