The structure of a light-sensitive G protein-coupled receptor in complex with a Gi-protein heterotrimer provides a structural foundation for the role of the receptor C-terminal tail in scaffolding and signaling.
The AAA+ protein unfolding motor ClpX grips substrates with the uppermost part of its substrate-binding pore, and requires interactions with hydrophobic amino acid side chains to operate with optimal efficiency.
Facing discrepancies in the sensory environment, multisensory information is combined in the medial superior parietal cortex to guide immediate judgements and to also adjust subsequent unisensory perception.
Analysis of axial polarity distributions shows that Wnt5a regulates collective cell migration in vivo by stabilizing vinculin at adherens junctions and fine-tuning mechanocoupling between neighbouring cells.
Super-resolution imaging reveals that the microtubule-associated protein Tau regulates the Fyn kinase organisation in dendrites, and that the frontotemporal dementia mutant Tau promotes aberrant Fyn clustering, potentially leading to synaptic dysfunction.
Robust wrinkling pattern of the frilled dragon’s spectacular erectile ruff emerges from an elastic instability during homogeneous growth of the embryonic neck fold frustrated by its attachment to adjacent tissues.
Parasitic helminths infect over a billion humans and use unusual anaerobic metabolism that needs a rare electron carrier, Rhodoquinone (RQ), whose synthesis requires the kynurenine pathway of tryptophan degradation.
Single episodes of voluntary exercise induced a functional increase in hippocampal synapses mediated by activity-dependent expression of the BAR protein Mtss1L, acting as a novel early effector of synapse formation.
Enhancements to the CUT&RUN antibody-targeted nuclease strategy for chromatin profiling include an improved affinity-cleavage fusion protein and digestion protocol, and a simplified calibration strategy.
Single-cell analysis of the chloroplast redox response to high light and oxidative stress revealed light-dependent heterogeneity, and was linked to cell fate determination within isogenic diatom populations.
Multi-site FRET measurements of moPrP oligomerization at low pH indicate that major conformational changes take place as monomers reversibly transform into large oligomers, which subsequently disassemble reversibly into small oligomers.
Single-cell RNA sequencing of neonatal uterus revealed an Misr2+ endometrial stromal progenitor whose inhibition by ectopic administration of MIS caused uterine hypoplasia and infertility in adulthood.
The sharp expression pattern driven by a classic, simple animal enhancer is determined by multiple molecular mechanisms, not only cooperative binding of the activating transcription factor as was previously thought.
A hub in the rostral anterior cingulate cortex receives unusually high and functionally diverse inputs, providing a biological interface between motivation, incentive based learning, and decision making.
Muscarinic acetylcholine receptor type A in adult Drosophila inhibits Kenyon cells, and is required for aversive olfactory learning and learning-associated synaptic depression between Kenyon cells and their output neurons.
In Streptomyces, the nucleoid-associated protein Lsr2 functions as a xenogenic silencer of foreign genes, and as a metabolic gatekeeper, repressing expression of both cryptic and well-studied specialized metabolic biosynthetic clusters.
An internet-based cohort study of paired associate learning shows that a first-degree family history of dementia is associated with lowered performance, an effect modified by apolipoprotein E genotype and diabetes.
VRAC activation, observed with a FRET sensor of intracellular LRRC8-domains movement during gating and by fluorometry, requires plasma membrane localization and diacylglycerol signaling, but is independent of intracellular ionic strength.
Optimised genome editing in P. knowlesi enables transgenic expression of a lead P. vivax vaccine candidate, revealing roles in host cell tropisms and providing tools for scalable vaccine efficacy testing.
Mass spectrometry analysis of purified pre-ribosomal RNAs shows that stable ribosomal RNA domains independently recruit assembly factors, and the cryo-EM structure of the 5' ETS ribonucleoprotein reveals regulatory conformational switches.
Combination of stem cell engineering and CRISPR technologies created a facile method to genetically manipulate macrophages, a multifunctional cell type that plays critical roles in immunity, cancer, and tissue homeostasis.
Heat shock induces relocalization of epigenetic modifiers to the nucleolus, which acts as a dedicated protein quality control center that is indispensable for recovery of epigenetic regulators and epigenetic modifications.
Recruitment of HOPS tethering complex to target membranes to promote vesicle fusions requires proper complex assembly and specific small GTPases, and HOPS is not transformed from the related miniCORVET complex.
A novel metabolic network analysis method enables large-scale computational predictions of biosynthetic capabilities across the human oral microbiome, revealing a unique cluster of fastidious microorganisms and potential metabolic interdependencies.
Activity in the dorsomedial prefrontal cortex encodes relative subjective value in a common neural code across decision-making for self and other and across tasks with divergent cognitive requirements.
Early in mammalian epidermal development, basal epidermal progenitor cells utilize packing and three-dimensional geometry, rather than cortical polarity cues, to inform division orientation and progenitor cell fate.
Structural and biochemical studies indicate that AAA+ ATPase employ a general mechanism to translocate a variety of substrates, including extended polypeptides, hairpins, crosslinked chains, and chains conjugated to other molecules.
The activation and membrane localization of the broadly-tuned noxious chemosensory cation channel TRPA1 are regulated by direct interactions with cholesterol via CRAC motifs in transmembane segments 2 and 4.
To protect their food and themselves against detrimental mould fungi, the eggs of a wasp species synthesize and emit remarkable amounts of gaseous nitrogen oxides that are highly effective antimicrobials.
A network of the gut chemical landscape predicts microbe-mediated biotransformation of foods and drugs and supports the generation of mechanistic hypotheses of microbiome metabolic phenotypes that shape human biology.
Newly discovered interaction between fission yeast SPB and animal centriole components reveals that pericentrin not only functions as a microtubule-nucleator, but also promotes centriole assembly in animals.
Precisely sequenced patterns of neuronal activity associated with the production of a skilled behavior begin and end as part of orchestrated activity across functionally diverse populations of cortical premotor neurons.
Proinsulin misfolding, an established cause of diabetes in patients with INS gene mutations, is now observed in normal human pancreatic islets, and rodents with genetic predisposition to type 2 diabetes.
Real-time monitoring of oxytocin-loaded vesicles and synaptic actin dynamics in zebrafish reveal that Slit3-Robo2-Cdc42 signalling maintains steady-state levels of mature oxytocin neuropeptide readily primed to be secreted upon physiological demand.
The contractile ring actin binding proteins tropomyosin Cdc8 and a-actinin Ain1 synergize to effectively compete with the endocytic actin patch protein fimbrin Fim1 for associating with F-actin networks.
The ability to follow single objects in 3D in a living organism with high spatiotemporal resolution opens new possibilities for quantitative biophysical studies of complex systems in their physiological context.
Par-complex-dependent cell polarity can be cell-autonomously conferred to non-polar Drosophila S2 cells, unveiling temporal patterns toward the cortical localization of Par-complex aggregates that include a meshwork containing unit segments.
Previously uncharacterized long repeat sequences are associated with significant genome variation that can increase fitness and promote antifungal drug resistance in diverse isolates of Candida albicans.
The endoplasmic reticulum E3 ubiquitin ligase Doa10 and the mitochondrial AAA-ATPase Msp1 govern targeting fidelity of outer mitochondrial tail-anchored proteins by controlling cytoplasmic concentration and extracting mistargeted and orphan species.
The modularity and unequivocal input/response of Notch signaling are harnessed to measure cell-surface shedding of diverse transmembrane receptors to identify new proteolytic switches and detect modulation of proteolysis by therapeutics.
Unique methodology was used to generate a large HDX-MS dataset to inform ligand-mediated activation of RORγ, an approach that can be extended to other nuclear receptors with unresolved ligand-dependent activities.
Single molecule subunit counting, FRET and electrophysiology experiments reveal that metabotropic glutamate receptor subunits interact and rearrange at the level of the transmembrane domains in response to allosteric modulators.
The expression of the lipoprotein lipase (LPL) transporter GPIHBP1 in glioma capillaries promotes the LPL-mediated processing of triglyceride-rich lipoproteins, thereby providing lipid nutrients for glioma cells.
Arp2/3 complex-mediated actin polymerization shapes how B lymphocytes probe the surface of antigen-presenting cells, promotes coalescence of B cell receptor (BCR) microclusters, amplifies BCR signaling, and enhances B cell activation.