Sigma1 Regulates Lipid Droplet-mediated Redox Homeostasis Required for Prostate Cancer Proliferation.

Unlabelled: Lipid droplets (LD) are dynamic organelles that serve as hubs of cellular metabolic processes. Emerging evidence shows that LDs also play a critical role in maintaining redox homeostasis and can mitigate lipid oxidative stress. In multiple cancers, including prostate cancer, LD accumulation is associated with cancer aggressiveness, therapy resistance, and poor clinical outcome.

In-depth polarisation resolved SHG microscopy in biological tissues using iterative wavefront optimisation.

Polarised nonlinear microscopy has been extensively developed to study molecular organisation in biological tissues, quantifying the response of nonlinear signals to a varying incident linear polarisation. Polarisation Second harmonic Generation (PSHG) in particular is a powerful tool to decipher sub-microscopic modifications of fibrillar collagen organisation in type I and III collagen-rich tissues. The quality of SHG imaging is however limited to about one scattering mean free path in depth (typically 100 micrometres in biological tissues), due to the loss of focus quality, induced by wavefront aberrations and scattering at even larger depths.

Effects of Solution Structure on the Folding of Lysozyme Ions in the Gas Phase.

The fidelity between the structures of proteins in solution and protein ions in the gas phase is critical to experiments that use gas-phase measurements to infer structures in solution. Here we generate ions of lysozyme, a 129-residue protein whose native tertiary structure contains four internal disulfide bonds, from three solutions that preserve varying extents of the original native structure. We then use cation-to-anion proton-transfer reactions (CAPTR) to reduce the charge states of those ions in the gas phase and ion mobility to probe their structures.

Native-Like and Denatured Cytochrome c Ions Yield Cation-to-Anion Proton Transfer Reaction Products with Similar Collision Cross-Sections.

The relationship between structures of protein ions, their charge states, and their original structures prior to ionization remains challenging to decouple. Here, we use cation-to-anion proton transfer reactions (CAPTR) to reduce the charge states of cytochrome c ions in the gas phase, and ion mobility to probe their structures. Ions were formed using a new temperature-controlled nanoelectrospray ionization source at 25 °C.

Folding of Protein Ions in the Gas Phase after Cation-to-Anion Proton-Transfer Reactions.

The structure and folding of a protein in solution depends on noncovalent interactions within the protein and those with surrounding ions and molecules. Decoupling these interactions in solution is challenging, which has hindered the development of accurate physics-based models for structure prediction. Investigations of proteins in the gas phase can be used to selectively decouple factors affecting the structures of proteins.