Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts:a possible defense against transforming growth factor-β mediated fibrosis

BACKGROUND: Mechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts' response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.

METHODS AND RESULTS: The effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.

CONCLUSION: We postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.

The Kepler-454 system: a small, not-rocky inner planet, a Jovian world, and a distant companion

Kepler-454 (KOI-273) is a relatively bright (V = 11.69 mag), Sun-like star that hosts a transiting planet candidate in a 10.6 day orbit. From spectroscopy, we estimate the stellar temperature to be 5687 ± 50 K, its metallicity to be [m/H] = 0.32 ± 0.08, and the projected rotational velocity to be v sin i <2.4 km s^-1. We combine these values with a study of the asteroseismic frequencies from short cadence Kepler data to estimate the stellar mass to be , the radius to be 1.066 ± 0.012 R_o, and the age to be Gyr. We estimate the radius of the 10.6 day planet as 2.37 ± 0.13 R_⊕. Using 63 radial velocity observations obtained with the HARPS-N spectrograph on the Telescopio Nazionale Galileo and 36 observations made with the HIRES spectrograph at the Keck Observatory, we measure the mass of this planet to be 6.8 ± 1.4 M_⊕. We also detect two additional non-transiting companions, a planet with a minimum mass of 4.46 ± 0.12 M_J in a nearly circular 524 day orbit and a massive companion with a period >10 years and mass >12.1 M_J. The 12 exoplanets with radii ⊕ and precise mass measurements appear to fall into two populations, with those ⊕ following an Earth-like composition curve and larger planets requiring a significant fraction of volatiles. With a density of 2.76 ± 0.73 g cm^-3, Kepler-454b lies near the mass transition between these two populations and requires the presence of volatiles and/or H/He gas.

Bio-fuelling the Hummer? Transdisciplinary Thoughts on Techno-Optimism and Innovation in the Transition from Unsustainability

An overarching aim of this chapter is to offer an informed and critical analysis of ‘techno-optimism’, informed by an explicitly transdisciplinary approach. A transdisciplinary perspective is one in which knowledge production goes beyond the academy to include end non-academic stakeholders and users. In effect it seeks to ‘upstream’ the involvement of non-academic interests in research design and knowledge production, as opposed to limiting those non-academic interests to the dissemination end point stage of research, which is the dominant research model. Techno-optimism is understood as an exaggerated and unwarranted belief in human technological abilities to solve problems of unsustainability while minimising or denying the need for large-scale social, economic and political transformation. More specifically, techno-optimism is the belief that the negative environmental and social costs of high-consumption, affluent, consumer societies and associated ways of life within capitalist orthodox economic growth orientated socio-economic systems, can be solved or eradicated through technological innovation and breakthroughs. Business as usual can be ‘greened’; a capitalist, growth-based economy can be made more ‘resource efficient’, consumerism less ‘resource intensive’ (and maybe a little bit more ethical). Techno-optimism, to be deliberately provocative for a moment, can therefore be described as a ‘biofuel the hummer’ response to the challenges (and opportunities) of the crisis of unsustainability. What I mean by that analogy is the seductive promise and premise of techno-optimism of not questioning or doubting the status quo (the hummer), hence it’s putative (but entirely false) non-political character. The capitalist, consumerist, growth-based socio-economic system is thus removed from critical analysis (usually on the implicit or explicit assumption of either the normative rightness of this system, or on strategic political grounds that it is naive or utopian to envisage widespread support for a non or post-capitalist consumer system). Techno-optimism simply enables a different means (biofuel) to the same ends.