Fueling a net-zero future: The influence of government-funded research on climate change mitigation inventions
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Sustainable urban systems (SUS) science is a new science integrating work across established and emerging disciplines, using diverse methods, and addressing issues at local, regional, national, and global scales. Advancing SUS requires the next generation of scholars and practitioners to excel at synthesis across disciplines and possess the skills to innovate in the realms of research, policy, and stakeholder engagement. Here, we outline key tenets of graduate education in SUS, informed by historical and global perspectives. The sketch is an invitation to discuss how graduates in SUS should be trained to engage with the challenges and opportunities presented by continuing urbanization.
Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of vitamin D receptor (VDR) signaling with the VDR ligands calcitriol or eldecalcitol prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of the 3 tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ΔRING mice afforded temporary or sustained protection from GC excess in bone or skeletal and heart muscle. We concluded that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the 3 tissues.