Hartleybauer4817

Many problems in mechanobiology urgently require characterization of the micromechanical properties of cells and tissues. Brillouin light scattering has been proposed as an emerging optical elastography technique to meet this need. However, the information contained in the Brillouin spectrum is still a matter of debate because of fundamental problems in understanding the role of water in biomechanics and in relating the Brillouin data to low-frequency macroscopic mechanical parameters. Here, we investigate this question using gelatin as a model system in which the macroscopic physical properties can be manipulated to mimic all the relevant biological states of matter, ranging from the liquid to the gel and the glassy phase. We demonstrate that Brillouin spectroscopy is able to reveal both the elastic and viscous properties of biopolymers that are central to the structure and function of biological tissues.The tendon enthesis is a fibrocartilaginous tissue critical for transfer of muscle forces to bone. Enthesis pathologies are common, and surgical repair of tendon to bone is plagued by high failure rates. At the root of these failures is a gap in knowledge of how the tendon enthesis is formed and maintained. We tested the hypothesis that the primary cilium is a hub for transducing biophysical and hedgehog (Hh) signals to regulate tendon enthesis formation and adaptation to loading. Primary cilia were necessary for enthesis development, and cilia assembly was coincident with Hh signaling and enthesis mineralization. Cilia responded inversely to loading; increased loading led to decreased cilia and decreased loading led to increased cilia. SBI-477 price to loading were dependent on Hh signaling through cilia. Results imply a role for tendon enthesis primary cilia as mechanical responders and Hh signal transducers, providing a therapeutic target for tendon enthesis pathologies.In bacteria, adenosine 5'-triphosphate (ATP)-binding cassette (ABC) importers are essential for the uptake of nutrients including the nonreducing disaccharide trehalose, a metabolite that is crucial for the survival and virulence of several human pathogens including Mycobacterium tuberculosis SugABC is an ABC transporter that translocates trehalose from the periplasmic lipoprotein LpqY into the cytoplasm of mycobacteria. Here, we report four high-resolution cryo-electron microscopy structures of the mycobacterial LpqY-SugABC complex to reveal how it binds and passes trehalose through the membrane to the cytoplasm. A unique feature observed in this system is the initial mode of capture of the trehalose at the LpqY interface. Uptake is achieved by a pivotal rotation of LpqY relative to SugABC, moving from an open and accessible conformation to a clamped conformation upon trehalose binding. These findings enrich our understanding as to how ABC transporters facilitate substrate transport across the membrane in Gram-positive bacteria.Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked fibrosis and low immunogenicity, features that are linked to treatment resistance and poor clinical outcomes. Therefore, understanding how PDAC regulates the desmoplastic and immune stromal components is of great clinical importance. We found that acyl-CoA synthetase long-chain 3 (ACSL3) is up-regulated in PDAC and correlates with increased fibrosis. Our in vivo results show that Acsl3 knockout hinders PDAC progression, markedly reduces tumor fibrosis and tumor-infiltrating immunosuppressive cells, and increases cytotoxic T cell infiltration. This effect is, at least in part, due to decreased plasminogen activator inhibitor-1 (PAI-1) secretion from tumor cells. Accordingly, PAI-1 expression in PDAC positively correlates with markers of fibrosis and immunosuppression and predicts poor patient survival. We found that PAI-1 pharmacological inhibition strongly enhances chemo- and immunotherapeutic response against PDAC, increasing survival of mice. Thus, our results unveil ACSL3-PAI-1 signaling as a requirement for PDAC progression with druggable attributes.Volcanic emissions are a critical pathway in Earth's carbon cycle. Here, we show that aerial measurements of volcanic gases using unoccupied aerial systems (UAS) transform our ability to measure and monitor plumes remotely and to constrain global volatile fluxes from volcanoes. Combining multi-scale measurements from ground-based remote sensing, long-range aerial sampling, and satellites, we present comprehensive gas fluxes-3760 ± [600, 310] tons day-1 CO2 and 5150 ± [730, 340] tons day-1 SO2-for a strong yet previously uncharacterized volcanic emitter Manam, Papua New Guinea. #link# The CO2/ST ratio of 1.07 ± 0.06 suggests a modest slab sediment contribution to the sub-arc mantle. We find that aerial strategies reduce uncertainties associated with ground-based remote sensing of SO2 flux and enable near-real-time measurements of plume chemistry and carbon isotope composition. Our data emphasize the need to account for time averaging of temporal variability in volcanic gas emissions in global flux estimates.Earth's upper mantle, as sampled by mid-ocean ridge basalts (MORBs) at oceanic spreading centers, has developed chemical and isotopic heterogeneity over billions of years through focused melt extraction and re-enrichment by recycled crustal components. Chemical and isotopic heterogeneity of MORB is dwarfed by the large compositional spectrum of lavas at convergent margins, identifying subduction zones as the major site for crustal recycling into and modification of the mantle. The fate of subduction-modified mantle and if this heterogeneity transmits into MORB chemistry remains elusive. Here, we investigate the origin of upper mantle chemical heterogeneity underneath the Western Gakkel Ridge region in the Arctic Ocean through MORB geochemistry and tectonic plate reconstruction. We find that seafloor lavas from the Western Gakkel Ridge region mirror geochemical signatures of an Early Cretaceous, paleo-subduction zone, and conclude that the upper mantle can preserve a long-lived, stationary geochemical memory of past geodynamic processes.