Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and β-adrenoceptors

The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2 subtype providing a secondary backup role. Bladder relaxation, which is required for urine storage, is mediated by β-adrenoceptors, in most species involving a strong β3-component. An excessive stimulation of contraction or a reduced relaxation of the detrusor smooth muscle during the storage phase of the micturition cycle may contribute to bladder dysfunction known as the overactive bladder. Therefore, interference with the signal transduction of these receptors may be a viable approach to develop drugs for the treatment of overactive bladder. The prototypical signaling pathway of M3 receptors is activation of phospholipase C (PLC), and this pathway is also activated in the bladder. Nevertheless, PLC apparently contributes only in a very minor way to bladder contraction. Rather, muscarinic-receptor-mediated bladder contraction involves voltage-operated Ca2+ channels and Rho kinase. The prototypical signaling pathway of β-adrenoceptors is an activation of adenylyl cyclase with the subsequent formation of cAMP. Nevertheless, cAMP apparently contributes in a minor way only to β-adrenoceptor-mediated bladder relaxation. BKCa channels may play a greater role in β-adrenoceptor-mediated bladder relaxation. We conclude that apart from muscarinic receptor antagonists and β-adrenoceptor agonists, inhibitors of Rho kinase and activators of BKCa channels may have potential to treat an overactive bladder

Nonlinear response of nitric oxide fluxes to fertilizer inputs and the impacts of agricultural intensification on tropospheric ozone pollution in Kenya

Crop yields in sub-Saharan Africa remain stagnant at 1 ton ha−1, and 260 million people lack access to adequate food resources. Order-of-magnitude increases in fertilizer use are seen as a critical step in attaining food security. This increase represents an unprecedented input of nitrogen (N) to African ecosystems and will likely be accompanied by increased soil emissions of nitric oxide (NO). NO is a precursor to tropospheric ozone, an air pollutant and greenhouse gas. Emissions of NO from soils occur primarily during denitrification and nitrification, and N input rates are a key determinant of emission rates. We established experimental maize plots in western Kenya to allow us to quantify the response function relating NO flux to N input rate during the main 2011 and 2012 growing seasons. NO emissions followed a sigmoid response to fertilizer inputs and have emission factors under 1% for the roughly two-month measurement period in each year, although linear and step relationships could not be excluded in 2011. At fertilization rates above 100 kg N ha−1, NO emissions increased without a concomitant increase in yields. We used the geos-chem chemical transport model to evaluate local impacts of increased NO emissions on tropospheric ozone concentrations. Mean 4-hour afternoon tropospheric ozone concentrations in Western Kenya increased by up to roughly 2.63 ppbv under fertilization rates of 150 kg N ha−1 or higher. Using AOT40, a metric for assessing crop damage from ozone, we find that the increased ozone concentrations result in an increase in AOT40 exposure of approximately 110 ppbh for inputs of 150 kg N ha−1 during the March–April–May crop growing season, compared with unfertilized simulations, with negligible impacts on crop productivity. Our results suggest that it may be possible to manage Kenyan agricultural systems for high yields while avoiding substantial impacts on air quality

Corporate Sustainability and Responsibility in Ecotourism: Entrepreneurial Motivation Enacted Through Sustainability Objectives

Corporate Sustainability and Responsibility (CSR) refers to organisational behaviours dedicated to the responsible use of natural resources, sensitivity to social capital or host culture and the sustainable distribution of economic wealth. These behaviours create social value and are in the interest of wider society. Organisations, including those who operate within the tourism industry, have been under longstanding social pressure to exhibit CSR behaviours. This social pressure has ultimately contributed to the emergence of sustainable tourism forms such as ecotourism. However, as this chapter recounts, there is no guarantee that the sustainability premise on which ecotourism has been founded will equate to actual responsible business behaviours. This chapter identifies that social and environmental failings observed within ecotourism may be a result of poor community consultation, ineffective ecotourism management and ‘inauthentic’ entrepreneurial motivations. It argues that should these failings be addressed, ecotourism does hold some potential to positively contribute to the tourism industries’ engagement with both sustainable and responsible behaviour. In part, this potential is dependent upon an ability to attract ‘altruistically motivated’ entrepreneurs to ecotourism business start-up, as these entrepreneurial types may represent a more reliable exponent of sustainable business behaviours. This proposition would be further supported where altruistic motivation is coupled with responsive ecotourism development, management and consultation. There is a role then for government and other tourism industry stakeholders to develop and offer support and management mechanisms for altruistically motivated ecotourism developments

Buruli ulcer : history and disease burden

A major objective of this open access book is to summarize the current status of Buruli Ulcer (BU) research for the first time. It will identify gaps in our knowledge, stimulate research and support control of the disease by providing insight into approaches for surveillance, diagnosis, and treatment of Buruli Ulcer. Book chapters will cover the history, epidemiology diagnosis, treatment and disease burden of BU and provide insight into the microbiology, genomics, transmission and virulence of Mycobacterium ulcerans. ; Supports further investigation by summarizing state of the art in the field of Buruli ulcer research Enriches understanding of epidemiology of Buruli ulcer in different geographic regions Reviews exhaustively the characteristics of Mycobacterium ulcerans diseas