Urban and transport planning, environment and health

The world is currently witnessing its largest urban growth in human history. Over 50% of people worldwide live in cities and this figure is estimated to increase to up to 70% over the next 20 years. Cities have long been known to be society’s predominant engine of innovation and wealth creation, but they are also a main source of pollution, crime and disease. Well-designed and efficient urban and transport systems are essential for cities and their citizens to thrive. Yet, the reality is that current urban and transport development have been less than optimal, creating and exacerbating human exposures to motor vehicle crashes, air pollution, noise, heat islands, lack of green space and sedentary behaviour, to name a few. These trends are associated with a large global burden of disease that has the potential to cripple even the best health care systems. This chapter provides an introduction to the many environmental and health issues that cities face as a result of urban and transport planning and policies. Some examples assessing the health impacts of urban and transport policies are overviewed. Different paradigms for cities and different city initiatives are overviewed. Finally, an introduction to the following chapters is provided

The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy

<div><p>Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (<i>Egfr</i>) to be critical for endometrial function during early pregnancy. While ablation of <i>Her2</i> or <i>Erbb3</i> led to only a modest reduction in litter size, mice lacking <i>Egfr</i> expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place <i>Egfr</i> in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of <i>Egfr</i>, wingless-related MMTV integration site 4 (<i>Wnt4</i>) or boneless morphogenic protein 2 (<i>Bmp2</i>); revealing that not only are <i>Bmp2</i> and <i>Wnt4</i> key downstream effectors of <i>Egfr</i>, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that <i>EGFR</i> is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries <i>WNK1</i> and <i>AKT1S1</i>, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.</p></div

Differential Phosphorylation of Perilipin 1A at the Initiation of Lipolysis Revealed by Novel Monoclonal Antibodies and High Content Analysis

Lipolysis in adipocytes is regulated by phosphorylation of lipid droplet-associated proteins, including perilipin 1A and hormone-sensitive lipase (HSL). Perilipin 1A is potentially phosphorylated by cAMP(adenosine 3′,5′-cyclic monophosphate)-dependent protein kinase (PKA) on several sites, including conserved C-terminal residues, serine 497 (PKA-site 5) and serine 522 (PKA-site 6). To characterize perilipin 1A phosphorylation, novel monoclonal antibodies were developed, which selectively recognize perilipin 1A phosphorylation at PKA-site 5 and PKA-site 6. Utilizing these novel antibodies, as well as antibodies selectively recognizing HSL phosphorylation at serine 563 or serine 660, we used high content analysis to examine the phosphorylation of perilipin 1A and HSL in adipocytes exposed to lipolytic agents. We found that perilipin PKA-site 5 and HSL-serine 660 were phosphorylated to a similar extent in response to forskolin (FSK) and L-γ-melanocyte stimulating hormone (L-γ-MSH). In contrast, perilipin PKA-site 6 and HSL-serine 563 were phosphorylated more slowly and L-γ-MSH was a stronger agonist for these sites compared to FSK. When a panel of lipolytic agents was tested, including multiple concentrations of isoproterenol, FSK, and L-γ-MSH, the pattern of results was virtually identical for perilipin PKA-site 5 and HSL-serine 660, whereas a distinct pattern was observed for perilipin PKA-site 6 and HSL-serine 563. Notably, perilipin PKA-site 5 and HSL-serine 660 feature two arginine residues upstream from the phospho-acceptor site, which confers high affinity for PKA, whereas perilipin PKA-site 6 and HSL-serine 563 feature only a single arginine. Thus, we suggest perilipin 1A and HSL are differentially phosphorylated in a similar manner at the initiation of lipolysis and arginine residues near the target serines may influence this process

Urban Wellbeing in the Contemporary City

The concept of well-being in the contemporary city refers to people’s ability to live healthy, creative and fulfilling lives. In this chapter, the intent is to understand theoretical perspectives about well-being research, essentially objective and subjective health and well-being of individuals in modern urban society. The emphasis is given to “non-medical” factors to determine the term by complex interactions between social, cultural, physical environments and individual behaviours. The chapter further indicates the tools and techniques adopted by researchers for measuring well-being emphasising the capability approach by Amartya Sen and Luc Boltanski’s approach on critical capacity. As a conclusion, based on the views and measures, the chapter suggests that addition of citizen science methodologies have potential utility for bridging objective and subjective perspectives of health and well-being, and influencing urban planning and design

Increasing water temperature triggers dominance of freshwater picoplankton

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