61 research outputs found
Connecting the dots in infrastructure development and management: The Africa agenda for new innovation
It is widely accepted that the growth and prosperity of nations is dependent on economic
infrastructure. Infrastructure is constituted by cyber-physical systems that enable
communications (e.g. postal, telephone and internet) as well as transportation (e.g. road,
water, air), energy (e.g. electricity and gas) and other utilities (e.g. drinking water and waste)
(Chandler, 1977; NAO, 2013). It provides the basis for economic growth and prosperity
through the provision of essential services that enable economic and social activity. As a
result, it delivers significant benefits, both directly through the services it delivers, and
indirectly through the impact of those services on the rest of the economy (Nightingale et al
2016). However, these benefits come at a cost. Infrastructure is expensive to build, operate
and maintain. The provision of infrastructure involves degradation and the consumption of
natural ecosystems, displacement of local communities, CO_{2} emissions, noise and pollution.
Infrastructure is typically long-lived and the costs of poor choices and mistakes can affect
future generations. This is especially prominent with politically motivated infrastructure
investment decisions, which have a lifespan that coincides with electoral cycles. To
complicate matters further, the costs and benefits of infrastructure provision fall unequally
across society in a way that benefits a minority (usually local to the area of infrastructure
development) although the distribution of costs are more widely spread (for example in
investments funded by taxes) (ibid). In this context, infrastructure investment decisions are
not only complex they are inherently political
Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells
Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and heart transplantation. A portion of familial DCM is due to mutations in the LMNA gene encoding the nuclear lamina proteins lamin A and C and without adequate treatment these patients have a poor prognosis. To get better insights into pathobiology behind this disease, we focused on modeling LMNA-related DCM using human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM). Primary skin fibroblasts from DCM patients carrying the most prevalent Finnish founder mutation (p.S143P) in LMNA were reprogrammed into hiPSCs and further differentiated into cardiomyocytes (CMs). The cellular structure, functionality as well as gene and protein expression were assessed in detail. While mutant hiPSC-CMs presented virtually normal sarcomere structure under normoxia, dramatic sarcomere damage and an increased sensitivity to cellular stress was observed after hypoxia. A detailed electrophysiological evaluation revealed bradyarrhythmia and increased occurrence of arrhythmias in mutant hiPSC-CMs on beta -adrenergic stimulation. Mutant hiPSC-CMs also showed increased sensitivity to hypoxia on microelectrode array and altered Ca2+ dynamics. Taken together, p.S143P hiPSC-CM model mimics hallmarks of LMNA-related DCM and provides a useful tool to study the underlying cellular mechanisms of accelerated cardiac degeneration in this disease
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