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Biology subjects

Urra, H.

Publications and source records attributed to Urra, H..

2 recordsLinked to original sources

Medium-assisted tumbling controls bacteria exploration in a complex fluid

In nature, many fluids that harbor bacterial populations or protect against microbial contamination exhibit non-Newtonian rheology. To study the spatial exploration of E.coli bacteria, a model multi-flagellated microorganism, in such complex environments, we design a motility medium with tunable macroscopic rheology. By increasing the solid charge in soft carbomer grains, we transition from a Newtonian viscous suspension to a yield-stress fluid. Using a 3D Lagrangian tracking device, we collect many individual bacterial tracks and characterize changes in motility properties such as swimming speed, persistence times and diffusivity for both a wild-type and a smooth runner mutant, up to the formation of a motility barrier at higher carbomer concentrations. We show that the presence of local mechanical disorder and resistance to penetration essentially override the biologically driven run-and-tumble navigation process. This "medium-assisted" exploration scenario is characterized by directional switching and stop-and-go kinematics and is closely related to the flexibility of the flagellar bundle.

biophysics↗

The endoplasmic reticulum stress sensor IRE1 regulates collagen secretion through the enforcement of the proteostasis factor P4HB/PDIA1 contributing to liver damage and fibrosis

Collagen is one the most abundant proteins and the main cargo of the secretory pathway, contributing to hepatic fibrosis and cirrhosis due to excessive deposition of extracellular matrix. Here we investigated the possible contribution of the unfolded protein response, the main adaptive pathway that monitors and adjusts the protein production capacity at the endoplasmic reticulum, to collagen biogenesis and liver disease. Genetic ablation of the ER stress sensor IRE1 reduced liver damage and diminished collagen deposition in models of liver fibrosis triggered by carbon tetrachloride (CCl4) administration or by high fat diet. Proteomic and transcriptomic profiling identified the prolyl 4-hydroxylase (P4HB, also known as PDIA1), which is known to be critical for collagen maturation, as a major IRE1-induced gene. Cell culture studies demonstrated that IRE1 deficiency results in collagen retention at the ER and altered secretion, a phenotype rescued by P4HB overexpression. Taken together, our results collectively establish a role of the IRE1/P4HB axis in the regulation of collagen production and its significance in the pathogenesis of various disease states.

cell biology↗