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  1. Free, publicly-accessible full text available April 5, 2023
  2. Abstract

    Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinialigand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the activated, open-channel state of a pLGIC by specific, state-dependent binding to this site.


    Misalignments between the rotation axis of stars and gas are an indication of external processes shaping galaxies throughout their evolution. Using observations of 3068 galaxies from the SAMI Galaxy Survey, we compute global kinematic position angles for 1445 objects with reliable kinematics and identify 169 (12 per cent) galaxies which show stellar-gas misalignments. Kinematically decoupled features are more prevalent in early-type/passive galaxies compared to late-type/star-forming systems. Star formation is the main source of gas ionization in only 22 per cent of misaligned galaxies; 17 per cent are Seyfert objects, while 61 per cent show Low-Ionization Nuclear Emission-line Region features. We identify the most probable physical cause of the kinematic decoupling and find that, while accretion-driven cases are dominant, for up to 8 per cent of our sample, the misalignment may be tracing outflowing gas. When considering only misalignments driven by accretion, the acquired gas is feeding active star formation in only ∼1/4 of cases. As a population, misaligned galaxies have higher Sérsic indices and lower stellar spin and specific star formation rates than appropriately matched samples of aligned systems. These results suggest that both morphology and star formation/gas content are significantly correlated with the prevalence and timescales of misalignments. Specifically, torques on misaligned gas discs are smaller for more centrallymore »concentrated galaxies, while the newly accreted gas feels lower viscous drag forces in more gas-poor objects. Marginal evidence of star formation not being correlated with misalignment likelihood for late-type galaxies suggests that such morphologies in the nearby Universe might be the result of preferentially aligned accretion at higher redshifts.

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  4. Free, publicly-accessible full text available March 1, 2023
  5. Free, publicly-accessible full text available March 1, 2023
  6. We present a new framework to understand how changes to the microstructure of cartilage lead to a mechanical phase transition.
    Free, publicly-accessible full text available February 11, 2023
  7. Articular cartilage is a collagen-rich tissue that provides a smooth, lubricated surface for joints and is also responsible for load bearing during movements. The major components of cartilage are water, collagen, and proteoglycans. Osteoarthritis is a degenerative disease of articular cartilage, in which an early-stage indicator is the loss of proteoglycans from the collagen matrix. In this study, confocal Raman microspectroscopy was applied to study the degradation of articular cartilage, specifically focused on spatially mapping the loss of glycosaminoglycans (GAGs). Trypsin digestion was used as a model for cartilage degradation. Two different scanning geometries for confocal Raman mapping, cross-sectional and depth scans, were applied. The chondroitin sulfate coefficient maps derived from Raman spectra provide spatial distributions similar to histological staining for glycosaminoglycans. The depth scans, during which subsurface data were collected without sectioning the samples, can also generate spectra and GAG distributions consistent with Raman scans of the surface-to-bone cross sections. In native tissue, both scanning geometries demonstrated higher GAG content at the deeper zone beneath the articular surface and negligible GAG content after trypsin degradation. On partially digested samples, both scanning geometries detected an ∼100 μm layer of GAG depletion. Overall, this research provides a technique with high spatial resolutionmore »(25 μm pixel size) to measure cartilage degradation without tissue sections using confocal Raman microspectroscopy, laying a foundation for potential in vivo measurements and osteoarthritis diagnosis.« less