The QacA DHA2 exporter from Staphylococcus aureus is a prototypical multidrug transporter that, like other bacterial efflux pumps, can extrude a wide range of cytotoxic compounds thus playing a crucial role in antimicrobial resistance. Here, we report crystal structures of wild-type QacA in three key conformational states: inward-open, outward-open and ethidium-bound, representing the first ligand-bound […]

Although many individuals with chronic aphasia respond to language therapy, there remains a need for adjunctive interventions that can enhance treatment response. Approaches targeting multiple modalities, such as gesture cueing, and neuromodulation techniques, such as transcranial magnetic stimulation, have shown promise for supporting language recovery. The present pilot study investigated whether enhancing activation of the […]

Background: Phelan McDermid syndrome (PMS), caused by SHANK3 haploinsufficiency, is a genetic form of autism spectrum disorder (ASD) that provides a genetically defined model for studying ASD-related circuit dysfunction. SHANK3 mutations disrupt synaptic organization and cortical synchrony, leading to attenuated gamma-band auditory steady-state responses (ASSRs). We investigated whether PMS-related electrophysiological signatures could be identified using […]

A hallmark of intelligent behavior is the ability to extract abstract relational structure from temporal sequences, recognizing, for instance, that seqaab, seqccd, and seqeef all follow the same underlying pattern, regardless of the specific elements involved. This capacity, observed across species and sensory modalities, is thought to underlie the formation of cognitive schemas: compressed internal […]

Alzheimer’s disease (AD) is defined by progressive tau aggregation, yet the molecular events driving this process remain poorly understood. Post-translational modifications (PTMs) are key regulators of tau biology and potential biomarkers of disease progression. Using immunoprecipitation-mass spectrometry and absolute quantification of tau isoforms, we profiled tau PTMs in soluble and insoluble brain fractions. We studied […]

Precise and minimally perturbative protein labelling remains a key challenge for studying biomolecular function in living systems. Here, a minimal way to specifically label proteins based on SNAP-tag and intein-mediated protein splicing reaction is introduced. Termed CLUSTER (for Chemical Label-Unfold-Splice Technology Enables Recombination), this chimeric platform supports efficient labelling across diverse targets in living cells […]

Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes to the liver, which drives patient mortality. CA19-9 is elevated in most PDAC tumors and is widely used as a clinical biomarker. Elevated serum levels are associated with poor outcomes. However, whether CA19-9 functionally contributes to metastatic progression has not been fully defined, in part because mice lack endogenous […]

1. Saproxylic community assembly is structured both by deadwood and forest habitat gradients, as well as biotic interactions such as competition, predation, and parasitism. However, covariation between abiotic and biotic conditions in natural systems have limited our ability to disentangle these mechanisms. Furthermore, focus towards beetles and fungi in temperate or boreal forests has led […]

Virus-targeted host proteins evolve under dual selective pressures. Negative selection preserves within-host interactions, while positive selection promotes adaptive changes to evade viral engagement. Viral and endogenous within-host partners can compete for binding, bringing distinct pressures together on the same interaction interface. Yet, the spatial organization of distinct selective pressures across virus-targeted host proteins, and how […]

Pests and pathogens reduce yields of major food crops by 15% globally. Interventions such as pesticides can mitigate yield loss, but pests can evolve resistance to pesticides over short timescales. Pest damage to crops may also be determined by (co)evolutionary selection on pests by crops themselves and vice versa, yet it is unclear whether the […]

Polyphosphate (polyP) is a conserved inorganic polymer traditionally viewed as a stress-induced phosphate and energy reserve. In cyanobacteria, however, polyP granules are constitutively present and frequently observed in proximity to carboxysomes, the bacterial microcompartments that mediate CO2 fixation. Here we show that polyP functions as a spatially organized regulator of the photosynthetic cytoplasm in Synechococcus […]

Formation of biological condensates through phase separation has emerged as a means of discrete subcellular organization permitting regulatory precision across diverse processes. We recently found that the conserved mitotic spindle positioning complex of Mushroom body defect (Mud) and Partner of Inscuteable (Pins) phase separates into condensates with dynamic, liquid-like properties. While the Mud/Pins complex functions […]