Global analysis of endogenous protein disorder in cells.

Disorder and flexibility in protein structures are essential for biological function but can also contribute to diseases, such as neurodegenerative disorders. However, characterizing protein folding on a proteome-wide scale within biological matrices remains challenging. Here we present a method using a bifunctional chemical probe, named TME, to capture in situ, enrich and quantify endogenous protein disorder in cells.

Tailored environments for directed mesenchymal stromal cell proliferation and differentiation using decellularized extracellular matrices in conjunction with substrate modulus.

Decellularised extracellular matrix (dECM) produced by mesenchymal stromal cells (MSCs) is a promising biomaterial for improving the ex vivo expansion of MSCs. The dECMs are often deposited on high modulus surfaces such as tissue culture plastic or glass, and subsequent differentiation assays often bias towards osteogenesis. We tested the hypothesis that dECM deposited on substrates of varying modulus will produce cell culture environments that are tailored to promote the proliferation and/or lineage-specific differentiation of MSCs.

Speed of lung inflation at birth influences the initiation of lung injury in preterm lambs.

Gas flow is fundamental for driving tidal ventilation and, thus, the speed of lung motion, but current bias flow settings to support the preterm lung after birth do not have an evidence base. We aimed to determine the role of gas bias flow rates to generate positive pressure ventilation in initiating early lung injury pathways in the preterm lamb. Using slower speeds to inflate the lung during tidal ventilation (gas flow rates 4-6 L/min) did not affect lung mechanics, mechanical power, or gas exchange compared with those currently used in clinical practice (8-10 L/min).

Cardiomyocyte intercellular signalling increases oxidative stress and reprograms the global- and phospho-proteome of cardiac fibroblasts.

Pathological reprogramming of cardiomyocyte and fibroblast proteome landscapes drive the initiation and progression of cardiac fibrosis. Although the secretome of dysfunctional cardiomyocytes is emerging as an important driver of pathological fibroblast reprogramming, our understanding of the downstream molecular players remains limited. Here, we show that cardiac fibroblast activation (αSMA) and oxidative stress mediated by the secretome of TGFβ-stimulated cardiomyocytes is associated with a profound reprogramming of their proteome and phosphoproteome landscape.