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Light could be used to measure the quantum ground state of a macroscopic mechanical resonator

Gallrein et al. pair functional assays with clocks to compare chronological versus biological age of single neuron types in C. elegans, to probe their vulnerability or resilience to neurodegeneration, and use an in silico screen to identify neuroprotective drugs.

Last November, a shock wave crippled Japan's Super-Kamiokande neutrino detector. David Cyranoski and Geoff Brumfiel find out how physicists plan to resurrect the device.

The recent mapping and modeling of protein-protein interfaces between general transcription factors TFIIE, TFIIH and Pol II have provided new insights into TFIIH-mediated melting of the transcription start site to form an open Pol II preinitiation complex and the stabilization of the complex by TFIIE, leading to a new mechanistic model for open-complex formation.

Many genetic studies focus on germline-inherited genomic variation. However, there is increasing realization that mutations occurring during our lifetime are so frequent and pervasive that, in all likelihood, no two of our cells are truly genetically identical. In this Review, the authors describe the detection, molecular nature and dynamics of this under-appreciated post-zygotic variation, and discuss the implications for normal human physiology and disease.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

A standardized, realistic phantom dataset consisting of ground-truth annotations for six diverse molecular species is provided as a community resource for cryo-electron-tomography algorithm benchmarking.

Fractional Chern insulators have been observed in moiré MoTe₂ at zero magnetic field, but the expected zero longitudinal resistance has not been demonstrated. Now it is shown that improving device quality allows this effect to appear.

Ribosomal translation is coupled to cotranslational protein folding, process assisted by dedicated chaperones. Here, authors present structures of the ribosome-bound yeast Hsp70 chaperone Ssb, identifying its ribosomal binding site and revealing its interactions with a model nascent chain.

Commercially available bionic hands can replicate many movements, but controlling a multiarticulate bionic hand is not an intuitive task. Here, the authors describe the integration of proximity and pressure sensors into a commercial prosthesis to enable autonomous grasping

VRACs are ubiquitously expressed osmosensitive ion channels assembled from LRRC8A-E subunits. Here, the authors determine the structures of a LRRC8A:D VRAC using cryo-EM and identified that these channels are gated by lipids inside the channel pore.

Piol et al. uncover that impaired eukaryotic initiation factor 5a (Eif5a) hypusination disrupts axonal translation and neuronal activity in fused in sarcoma-amyotrophic lateral sclerosis (FUS-ALS) by applying spatial transcriptomics in motor axons. In vitro and in vivo targeting Eif5a hypusination via spermidine supplementation improves ALS model phenotypes.

De novo design of Ca²⁺ channels with ion selectivity that can assemble appropriately and mediate Ca²⁺ conductance when expressed in cells is described.

Accurate spectral libraries are essential for analyzing data-independent acquisition (DIA) proteomics data. Here, the authors present Carafe, which trains on DIA data to build experiment-specific spectral libraries, boosting peptide detection across diverse datasets.

Proteomics must target specific synapse types to reveal how molecules shape their unique functions. Here, authors show that hippocampal synapses differ in proteome and that neuron-specific glutamate receptor regulation shapes synaptic diversity.

The Sustainable Development Goals map out a broad spectrum of objectives. Analytical tools in form of the Index and Dashboards provide a starting point to set national baselines, and allow comparison of the SDGs with other indices of well-being.

Cryo-EM structures of the stabilized prefusion conformation of the glycoprotein B ectodomain—the HSV-1 entry machine—identify a prefusion-specific neutralizing antibody and reveal how prefusion glycoprotein B may evade antibody-mediated neutralization.

Although FZDs are promising drug targets, so far no small molecules targeting them were described. Here, the authors report the a FZD7 core-targeting small molecule negative allosteric modulators of WNT-induced signaling, confirmed by pharmacology, structure determination and MD simulations.

Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely applicable to small protein targets.

Shared inter-brain neural dynamics, reflecting aspects of social interaction including self and other’s behaviours, arise in GABAergic neurons of the dorsomedial prefrontal cortex of socially interacting mice, as well as in the neurons of socially interacting artificial intelligence agents.

Li et al. show that a Lamassu defense system protects bacteria from phage infection by activating a lethal tetrameric DNA-cutting enzyme. In the absence of phages, a protein clamp holds the enzyme as an inactive monomer, preventing self-damage.

Photosystem II drives photosynthesis, but how desert algae adapt to excess of light remains unclear. Here, authors present a cryo-EM structure of PSII from Chlorella ohadii, revealing structural features and antenna arrangements that may contribute to its stability.

SLC35B1, initially thought to be a nucleotide sugar transporter, is an essential ATP/ADP exchanger that imports ATP into the endoplasmic reticulum through a unique stepwise translocation mechanism.

Plant mitoribosomes are crucial for mitochondrial protein synthesis. Here, authors use cryo-EM to determine high-resolution structures of cauliflower mitoribosomes, and combined with sequencing and mass spectrometry, identified 19 rRNA base modifications.

KCNQ1 (Kv7.1) channels are critical for heart rhythm homeostasis. Here, the authors report the KCNQ1 structure in an intermediate state, revealing unique S1–S2 conformations that illuminate channel gating and may aid targeted drug development.

Here, the authors examine how people combine facial expressions and context to understand others’ emotions. They find that most people use a Bayesian integration strategy, where cues are weighted based on ambiguity, but others use more simplistic averaging strategies.

The HKU25 clade MERS-related coronaviruses with broad distribution are shown to use ACE2 as a functional receptor, revealing unexpected receptor plasticity and offering new insights into coronavirus evolution, host range and potential zoonotic risk.

In single-particle cryo-EM, datasets often contain molecules that exist in a heterogeneous mix of states. Here, the authors compare different computational tools to study this heterogeneity and derive metrics to quantitatively compare their results.

Multidrug efflux pumps help bacteria survive stress and promote antibiotic resistance. Here, authors define the molecular detail of an anaerobic-connected pump MdtF uncovering acid-responsive activity which may enable toxin control in certain niches.

Zeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.

NBCn1 plays an important role as a base loader allowing breast cancer cells to survive in an acidic environment. Here, Wang et al report its near atomic structure and transport cycle involving minimal structural changes associated with an exceptionally high turnover rate, enabling efficient cellular base loading and tumor survival

A cryo-EM structure of SARS-CoV-2 ORF3a reveals a new fold conserved in coronaviruses, and functional experiments show ion channel activity that may be important for viral infectivity.

Durable agonism of NPR1 achieved with a novel investigational monoclonal antibody could mirror the positive hemodynamic changes in blood pressure and heart failure identified in humans with lifelong exposure to NPR1 coding variants.

Importin β, the prototypical eukaryotic nuclear import receptor, transports a wide variety of cargos into the nucleus. Ko et al. used cryogenic electron microscopy to reveal an unexpected allosteric regulation of Importin β’s affinity for FG-nucleoporins, triggered by Ran-GTP.

This study shows that, by age 4, children understand lexical causatives to refer to direct causes and periphrastic causatives to indirect causes in causal chains. Understanding causation by absence develops later in older children.

This study reveals the structural basis of auxin import by the AUX/LAX family. LAX3 binds auxin as well as herbicides via a proton-coupled mechanism, which offers insights into hormone recognition that is essential for lateral root growth.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

The GroEL/ES chaperonin can act during protein synthesis to promote folding. Here, Roeselová et al. show how GroEL captures, remodels and sequesters nascent proteins in its central chamber, while they remain tethered to the ribosome.

Deep learning-based generative tools are used to design protein building blocks with well-defined directional bonding interactions, allowing the generation of a variety of scalable protein assemblies from a small set of reusable subunits.

PIN transporters are key players in distributing phenoxyacetic acid herbicides. Mutagenesis and cryo-EM structures elucidate substrate specificity and transport mechanisms, paving the way for improved synthetic auxin development and herbicide-resistant crops.

Using cryo-electron microscopy, the interactions of Sestrin2 and CASTOR1 with GATOR2 were resolved, revealing how mTORC1 activation is regulated and how nutrient availability triggers signalling for cellular growth.

This is a Protocol for the derivation, expansion and cryopreservation of primary organoids from human amniotic fluid cells. These cells generate lung, kidney tubule and gastrointestinal epithelial organoids autologous to the developing fetus.

Alfajaro et al identify that a bat MERS-like coronavirus HKU5 uses ACE2 as a receptor from its natural bat reservoir Pipistrellus abramus and American mink. Structural analyses demonstrate a unique interaction between the HKU5 receptor binding domain and bat ACE2. This highlights the receptor flexibility of merbecoviruses and identifies mink as potential intermediate hosts, informing viral surveillance and countermeasure development.