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Riazanski et al describe a platform to capture extracellular vesicles (EVs) using a nanoporous silicon nitride membrane, investigate the expression of NHE1 protein on the surface of EVs and monitor the transport of Na+ and H+ at the single EV level. The authors report a mechanistic function of the proteins found in EVs and specifically identify NHE1 on a single EV, where it maintains pH neutrality within single vesicles.
Edmunds et al. examine how the adenosine receptor A2AR and the checkpoint molecule TIM3 suppress the killing of Renca tumors expressing hemagglutinin (HA) as a model neo-antigen by CL4 TCR transgenic T cells, which recognize an HA peptide presented by H-2Kd. The authors report that TIM3, which is upregulated on tumor-infiltrating CD8+ T cells after inhibition of A2AR, and A2AR impair the cytoskeletal polarization of the CL4 T cells.
Le et al. present cryo-EM structures of the peroxisomal very long chain fatty acid (VLCFA) transporter ABCD1 in phospholipid nanodiscs in a nucleotide-bound conformation open to the peroximsomal lumen and a conformation open to the cytosol. These structures provide the basis for structure-function studies to investigate VLCFA transport properties, disease-causing mutations, and drug design for disorders, such as X-linked adrenoleukodystrophy, associated with ABCD1 dysfunction.
Tsybovsky et. al. report cryo-EM structures of tetrameric rat ALDH1L1 elucidating its architecture and domain interactions important for its functions. These findings emphasize the versatility of acyl/peptidyl carrier proteins in complex, highly dynamic enzymatic systems.
Can et al. demonstrate the ability to use hyperpolarized [1-13C]pyruvate at nearphysiological concentrations to directly assess liver enzymatic activities by 13C magnetic resonance. While in the fed state, the normalized [13C]bicarbonate signal produced from hyperpolarized [1-13C]pyruvate derives from PDH activity, which is saturated at supraphysiological doses, it results from PEPCK in the fasted state and is dose-independent, allowing non-invasive in vivo detection of hepatic gluconeogenesis.”
Lyu and colleagues use theoretical models to examine the relationship between post-pairing male behaviors and female trait evolution. They find that male mate choosiness can be surprisingly influential on the evolution of costly female traits, but also that costly male preference and costly female traits could evolve to a polymorphic equilibrium under certain conditions.
Rafiq et al. report that disruption of JIP3-dependent control of axonal lysosome transport in human neurons results in unexpected changes to the organization of multiple cytoskeletal proteins. This study provides new insights that improve our understanding of intellectual disabilities caused by mutations in JIP3, and are relevant for neurodegenerative diseases associated with accumulations of lysosomes such as the Alzheimer’s disease
Miotto et al. perform molecular dynamics simulations on a selected set of possible SARS-CoV-2 spike variants in order to assess the stabilizing effect of particular amino acid substitutions on the molecular complex. Their analysis can help to monitor further possible spike variants.
