Search

The Middle Palaeolithic of southwest Asia witnessed interactions and knowledge sharing between archaic and modern humans ~130,000–80,000 years ago. These interactions led to increased behavioural complexity and consolidation of a uniform behavioural set across Homo groups in the region.

This genome-wide association study identifies 162 genetic loci linked to income, shedding light on the complex interplay between genetics, income, education and health.

Studies based on cryo-electron microscopy structures of Hsp90 chaperone complexes reveal the molecular mechanism of the chaperone-mediated maturation of the human glucocorticoid receptor.

The process of protein crystallization is poorly understood and difficult to program through the primary sequence. Here the authors develop a computational approach to designing three-dimensional protein crystals with prespecified lattice architectures with high accuracy.

The first apicomplexan, Chromera velia, with a functional photosynthetic plastid has been isolated and characterized, providing insight into early apicomplexan evolution.

Quantum annealing is expected to solve certain optimization problems more efficiently, but there are still open questions regarding the functioning of devices such as D-Wave One. A numerical and experimental investigation of its performance shows evidence for quantum annealing with 108 qubits.

E217 is a Myoviridae used in an experimental phage cocktail to eradicate Pseudomonas aeruginosa. Here, the authors utilize cryo-EM and functional analysis to delineate E217 structural proteins, tail dynamics, and mechanisms of host recognition.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

Cryo-electron microscopy of Azotobacter vinelandii FeSII–nitrogenase reveals a core complex of molybdenum–iron proteins (MoFePs), iron proteins (FePs) and FeSII, in which FeSII mediates interactions with MoFeP and FeP to position their FeS clusters in catalytically inactive but O₂-protected states.

Borzoi adapts the Enformer sequence-to-expression model to directly predict RNA-seq coverage, enabling the in-silico analysis of variant effects across multiple layers of gene regulation.

Combining structural, biochemical, cellular and in vivo assays, the authors uncover the mechanism for capture and multisite phosphorylation of lethal (2) giant larvae by the atypical protein kinase C and partitioning-defective protein 6, revealing the basis for their mutual antagonism underpinning cell polarity.

FANCD2–FANCI is a sliding clamp that diffuses on double-stranded DNA but stalls when it reaches a single-stranded gap, providing a unified molecular mechanism that reconciles the roles of FANCD2–FANCI in the recognition and protection of stalled replication forks.

Accurate segmentation of ischemic stroke lesions from brain MRI is crucial for timely diagnosis and treatment planning. Here, the authors present DeepISLES, an AI ensemble for stroke MRI analysis that outperforms previous methods and matches expert radiologist performance in identifying stroke lesions.

Cryo-EM analyses provide a near-atomic view of the C. elegans securin–separase complex, with insights into the mechanism by which securin inhibits separase's protease activity.

Epsilon toxin (Etx) is a potent pore forming toxin (PFT) produced by Clostridium perfringens. Here authors show the cryo-EM structure of the Etx pore assembled on the membrane of susceptible cells and shed light on pore formation and mutant phenotypes.

Combining conjugation and structural analyses, the authors show that TraN-OMP pairings determine bacterial conjugation species specificity, with implications in resistance plasmid distribution within Enterobacteriaceae.

The neuraminidase-targeting monoclonal antibody FNI9 potently inhibits the enzymatic activity of influenza A and B viruses via receptor mimicry.

The regulation of plasma glucose levels is effected by insulin. Here, the authors reveal atomic detail of how peptides distinct from insulin bind to and activate the insulin receptor, with implications for design of small-molecule insulin mimetics.

KCNQ1 channels are active in heart, brain and gut. Functional loss causes epilepsy and sudden arrhythmic death. Here, authors describe a key activator drug binding site, explaining isoform and drug selectivity, and point the way for new drug design.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

Upon encounter of abasic lesions, a highly-prevalent DNA damage, RNA polymerase I experiences a two-step pausing-stalling mechanism that is described here through cryo-EM analysis. The structures uncover the nucleotide entry mechanism and provide insights into intrinsic RNA cleavage.

Here the authors isolate monoclonal antibody HmAb64 from a healthy volunteer who received an experimental polyvalent DNA prime-protein boost HIV vaccine, and show that it’s specific for the CD4 binding site and neutralizes cross-subtype HIV isolates including several tier-2 viruses.

The authors present a public collection of 117 bacterial isolates from the pig gut, including the description of 38 novel taxa. Interesting functions discovered in these organisms include a new fucosyltransferease and sactipeptide-like molecules encoded by biosynthetic gene clusters.

Human islet amyloid polypeptide (hIAPP) is a protein commonly forming aggregates in islet cells of those afflicted by type II diabetes. New structures of fibrils seeded with patient-derived material reveal a diverse repertoire of structures, some of which may resemble those appearing in vivo.

RNA is a promising reservoir of new drug targets. Here, the authors introduce RNAmigos2, a structure-based deep learning model that speeds up screening by 10,000x while rivaling docking accuracy, showing success in identifying RNA-binding compounds in vitro.

Transport measurements in twisted bilayer MoTe₂ reveal quantized Hall resistance plateaus and composite Fermi liquid-like behaviour under zero magnetic field, constituting a direct observation of integer and fractional quantum anomalous Hall effects.

Detailed analyses of the serotonin receptor 5-HT_1A and the psychedelic 5-methoxy-N,N-dimethyltryptamine reveal the differences in receptor structural pharmacology that mediate signalling specificity, efficacy and potency, findings that may facilitate the development of new neuropsychiatric therapeutics.

Gasdermin D Cys191 is S-palmitoylated, and palmitoylation is required for pore formation.

Maurizi et al. introduce GraphMetaMat, a graph-based AI framework for designing 3D metamaterials with programmable nonlinear responses, enabling the inverse design of new structural and acoustic behaviours despite fabrication defects and limits.

Altered mechanotransduction has been proposed as a mechanism for disease pathophysiology, yet evidence remains scarce. Here, the authors show that antibodies from patients with bleeding disorders bind to integrins and modulate platelet cell contraction force, and this correlates with clinical symptoms.

The mechanisms underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) are unknown. Herein, the authors reveal that alcohol-induced microbial reorganization and resultant elevation in GMM phenylacetylglutamine, directly contributes to CVD.

Tetrahydrocannabinol (THC) analogs target the cannabinoid receptor CB1 for therapeutic and psychoactive effects. Here, the authors determine spatiotemporal ligand interactions critical for potency, efficacy, off-rates and drug design.

The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large subunit. Here the authors report the structure of Drg1 in complex with its specific inhibitor diazaborine and provide insight into the mechanism of inhibition and specificity of this class of inhibitors.

Ring deconvolution microscopy leverages symmetry to provide fast and straightforward spatially varying deblurring and offers improved speed and image quality compared to standard approaches across diverse microscopy modalities.

Government support for energy technology is vital, but quantifying its effects downstream is complicated. Towards this end, David Popp analyses scientific publication data resulting from public money, exploring the time lags between funding and new publications and the resulting policy implications.

GPAT1 is a mitochondrial outer membrane protein that catalyzes the first step of glycerolipid biosynthesis. Cryo-EM structures and functional studies of human GPAT1 uncover the molecular architecture and mechanism of this important acyltransferase.

PCprophet combines complex-level scoring and machine learning to predict novel protein complexes from protein cofractionation mass spectrometry data and to perform differential analysis across experimental conditions.

Single-molecule live-cell fluorescence in situ hybridization uses an RNA-targeting CRISPR–Csm complex to image and track endogenous RNAs.

Here, the authors use cryo-EM to solve the structures of seven potent human antibodies, and demonstrate in vivo protection in a liver burden assay, using chimeric Plasmodium berghei sporozoites expressing Plasmodium falciparum circumsporozoite protein.

Development of vaccines remains challenging because viral antigens can be unstable or aggregate. Here, authors present ancestral sequence reconstruction as a method to generate stable and soluble antigens using exclusively available sequence information.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation.

Mass photometry is a label-free optical approach capable of detecting, imaging and accurately measuring the mass of single biomolecules in solution. Here, the authors demonstrate the potential of mass photometry for quantitatively characterizing sample heterogeneity of purified protein complexes with implications for structural studies specifically and in vitro studies more generally.

How traits specific to modern humans have evolved is difficult to study. Here, Gokhman et al. compare measured and reconstructed DNA methylation maps of present-day humans, archaic humans and chimpanzees and find that genes that affect vocal tract and facial anatomy show methylation changes between archaic and modern humans.

The structure of myosin-2 in the shutdown state reveals how the shutdown state is stabilized and how phosphorylation of light chains allows myosin to be activated.

A nanoparticle influenza vaccine candidate is shown to induce broad cross-reactive antibody responses in animal models.

Intracellular potassium (K+) homeostasis is achieved by activity of both ion channels and transporters. Here, the authors report structures of E. coli glutathione (GSH)-gated K+ efflux transporter KefC with bound K+ and conclude that the ion-binding site is adapted for binding a dehydrated ion.