Direct sarcomere activating drugs (myotropes) have emerged as one alternative to inotropes in heart failure. The only myotropes that have been evaluated clinically involve myosin modulation, which does not increase maximum calcium activated tension (Tmax), observed in heart failure with reduced (HFrEF) and obese preserved (HFpEF) ejection fraction. Here, we tested if troponin modulation with the sarcomere activator CK-136 (1 uM) can augment Tmax. We isolated permeabilized myocytes from HFrEF (n = 5), HFpEF (n = 9, 5 w/severe obesity and reduced Tmax and 4 w/o), and non-failing human (n = 6) and porcine controls and obtained tension-Ca relationships with CK-136.
Microbial communities are found throughout the biosphere, from human guts to glaciers, from soil to activated sludge. Understanding the statistical properties of such diverse communities can pave the way to elucidate the common mechanisms ...Multiple ecological forces act together to shape the composition of microbial communities. Phyloecology approaches—which combine phylogenetic relationships between species with community ecology—have the potential to disentangle such forces but are often ...
Abstract Since its burst in early 2020, the Covid-19 pandemic has deeply affected every aspect of daily life, from international trade and travelling to restrictions on an individual level, becoming a complex multi-level and highly multi-faceted problem. Due to its overarching influence and deep impact, it can be seen as one of the most disruptive Grand Challenges of our time. Different from most other lasting Grand Challenges, such as Climate Change, the pandemic exerted its influence with little ramp-up, rapidly transforming health and health systems, human lives, goods and economic flows, decision-making mechanisms, research and innovation, and many other aspects of life in a very short span of time. Grand Challenges require extraordinary efforts from society as a whole since they need holistic, effective, collaborative endeavours to solve them. One such unique orchestrated effort can be observed in the subsequent series of virtual massive EUvsVirus ( https://www.euvsvirus.org/ ) events and committed collaborations (‘hackathon’, ‘matchathon’, ‘launchathon’, ‘community’, ‘EIC Covid platform’, and the unparalleled ‘Academia Diffusion Experiment’ [ADE], analysed in chapter “Academia Diffusion Experiment: Trailblazing the Emergence from Co-Creation” of this book). While this chapter explains ‘what’ has been produced with the ADE, inspired by the EUvsVirus phenomenon, the ADE chapter describes ‘how’ it has been done. Both are extremely unique in terms of content, procedure, motivation, collaboration, effects—and they attempt to trailblaze at highest level co-creation, co-evolution, and co-dreaming. Hence, situated as the last chapters of this book. This chapter will shed light on the EUvsVirus events, where over 30,000 individuals from 40 countries came together and addressed the complexity of this massive challenge in a pioneering and groundbreaking way. The chapter is focused on analysing the EUvsVirus hackathon (alongside its mentioned unique spillovers) as a tool, method, and process capable of channelling and activating individuals’ and institutions’ concerns, wills, and commitments into a unique orchestrated open, collaborative response to an urgent Grand Challenge, the pandemic. We are producing a multi-vortex tornado model, resembling the EUvsVirus phenomenon, its components, mechanisms, behaviour and how to replicate it to achieve such disruptive, global organisational effort of co-creation. Especially, the emergence of such collaboration in the face of such urgency leads to the assumption that there are crucial lessons to be learned from this endeavour, quite fittingly encapsulated by these words: ‘We are learning That though we weren't ready for this, We have been readied by it’. Amanda Gorman’s New Year poem ( https://amandagormanbooks.com/#the-hill-we-climb-and-other-poems or https://edition.cnn.com/videos/tv/2022/01/06/exp-amanda-gorman-nye-poem.cnn )
