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The activity of heat shock proteins (Hsp) is modified by binding to cochaperones. Here, the authors develop a four-colour FRET system to show that cochaperone p23 binding to Hsp90 strengthens the ATP-dependent directionality, thus validating their approach for the study of other multicomponent protein machines.

Cytokinetic-based rings for self-division of synthetic cells lack spatial control for the targeting of contractile forces within cell-like lipid vesicles. Here, authors combine actomyosin rings and the MinDE bacterial protein system to achieve ring positioning, equatorial furrowing and blebbing.

Triggering and sustaining fusion reactions — with the goal of overall energy production — in a tokamak plasma requires efficient heating. Radio-frequency heating of a three-ion plasma is now experimentally shown to be a potentially viable technique.

Cryo-EM analysis of the human apelin receptor activated by either the endogenous peptide ligand or a potent synthetic small-molecule agonist reveals a mixture of homodimer and monomer organizations shedding light on a versatile regulation mechanism.

Zhang et al. identify unimodal neural representations in the spinal cord of cutaneous mechanical and heat stimuli gated by a shared feed-forward local inhibitory neuron type and a neural transition during neuropathy, with increased excitatory drive.

Two recent studies have investigated the prevalence of anti-hLAMP-2 antibodies in patients with antineutrophil cytoplasmic antibody-associated vasculitides. Results from these studies suggest that more work is needed to standardize the assays used to detect anti-hLAMP-2 antibodies in patient sera before we can estimate their true prevalence in different patient populations and assess their potential clinical utility.

The nuclear periphery is linked with transcriptional repression, but MyoD1 remains active during myoblast proliferation despite being in this compartment. Here, the authors show that WFS1 tethers MyoD1 to the nuclear periphery via active enhancers.

How animals adapt to toxic ecological niches is poorly understood. This study shows that Drosophila busckii has evolved a tolerance to DMDS, a potent insecticide, likely due to an insensitivity in its cytochrome c oxidase (COX) enzyme complex.

The RNAse III endonuclease Dicer is crucial for processing of pre-miRNAs in health and disease. Here the authors show that endothelial Dicer promotes atherosclerosis by increasing miR-103 levels leading to suppression of the anti-inflammatory transcription factor KLF4, thus suggesting a novel approach to treat this disease.

Biocatalysis can take advantage of an enzyme's inherent reactivity regardless of its physiological role, as shown for a terpene cyclase turned Brønsted acid catalyst after its active site pocket was mutated while the activated aspartic acid was retained.

The mammalian transcription factors Oct4 and Pou2 are implicated in germ cell pluripotency induction and maintenance. Tapia and colleagues find that axolotl Pou2 and Oct4 reprogram mouse and human fibroblasts to a pluripotent state, suggesting ancestral Oct4 and Pou2 gene function is evolutionarily conserved.

Malnutrition is a key risk factor affecting children’s health and development. Here, the authors report long-term protection against malnutrition-induced enteropathy by a neonatal S100a8/a9 nutritional supply in mice.

Growth at liquid-liquid interfaces differ inherently from that on solids, making it attractive for nanomaterial formation. Here, the authors use X-ray scattering to derive a detailed microscopic picture of lead-halide growth on liquid mercury that reveals the key importance of anion adsorption.

Here, the authors show that cystatin C (CST3) regulates the activity of cathepsin B during pancreatitis in a pH dependent manner. Moreover, cathepsin B activity is inhibited by monomeric CST3 but activated by dimeric CST3.

Active matter exhibits a range of collective behaviors offering insights into how complex patterns can emerge at different length scales. Here, Hsu et al. confine active filaments on the spherical surface of a lipid vesicle and observe the formation of off-equator polar vortices and jammed patterns.

Co-transmission of neuropeptides and small molecule neurotransmitters represents a fundamental characteristic of neurons. Here, authors present a high-performance GRAB sNPF sensor and use it to reveal distinct spatiotemporal dynamics of sNPF and ACh release from single neurons.

Ubiquitin (Ub) and Ub-like modifiers (Ubls) can form chains of various topologies, but preparing defined chains for functional studies remains challenging. Here, the authors develop chemoenzymatic tools to tailormake Ub/Ubl chains and study the involvement of specific Ub/SUMO chains in DNA repair.

De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, the authors show that Cul3 is essential to regulate neuronal migration by tightly regulating Plastin3 (Pls3). Pls3 cell-autonomously regulates cell migration by regulating the actin cytoskeleton organization.

RNA binding protein HDLBP (or Vigilin) localizes in the endoplasmic reticulum (ER) membrane. Here the authors show that HDLBP contributes to translation of ER-targeted mRNAs.

Here the authors show that the patterning signals WNT, BMP, and FGF control chromosome segregation fidelity during early lineage specification and neurogenesis, which could provide a rationale for the spatio-temporal distribution of genomic mosaicism during human development.

In this study, the authors mutate histone H3.3 K9 and K27 residues, demonstrating their importance in maintaining repressive chromatin states at endogenous retrovirus-derived cryptic enhancers and bivalent promoters in mouse embryonic stem cells.

The herbivorous horseradish flea beetle sequesters plant toxins to defend against predators. Here the authors identify glucosinolate transporters expressed in the beetle Malpighian tubules and provide evidence that these reabsorb glucosinolates from the tubule lumen to prevent their loss by excretion.

A microwell chip facilitates the single-cell characterization of the differentiation of aggregates of human induced pluripotent stem cells into pancreatic duct-like organoids and the discovery of secreted markers of pancreatic carcinogenesis.

The t(8;21) translocation is often found in acute myeloid leukaemia but is not sufficient for development of the disease. In this study, the authors identify frequent mutations in the transcriptional repressor, ZBTB7A, in these patients and show that the mutations reduce DNA binding activity.

Insufficient glucagon signalling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Here the authors report that the amino acid sensitive calcium sensing receptor (CaSR) is necessary for α cell proliferation via Gq signalling during hyperaminoacidemia.

Stimulated emission depletion (STED) microscopy is compromised by the trade-off between resolution and photobleaching. Here, the authors present ReSTED, a reactivatable STED microscopy using fluorescence-recoverable nanographene that enables hour-long, super-resolution 3D imaging without bleaching.

Detailed mapping of the distribution of water and semiheavy water in the coma of Halley-type comet 12P implies a D/H ratio that is consistent with that of Earth’s water, indicating a common heritage.

This study demonstrates that cryo nanoscale secondary ion mass spectrometry (CryoNanoSIMS) enables direct multi-elemental imaging at subcellular resolution of macro- and micronutrients or trace elements in plants and may provide insights into the in vivo roles of many transporters.

Goal-directed behaviors require the brain to integrate information across many task-related dimensions. Here, the authors use a virtual context discrimination paradigm in mice to demonstrate the capacity for neurons in the retrosplenial cortex to exhibit multidimensional encoding across learning.

Global antibiotic scarcity looms owing to bacterial resistance. Now the discovery of a class of allosteric inhibitors targeting DNA gyrase—essential for bacteria—yields a compound LEI-800 that exhibits activity against fluoroquinolone-resistant E. coli. The compound’s unique mode of action, revealed through cryo-EM, makes it a promising candidate for countering bacterial resistance.

Rare mutations in the high requirement temperature protein A1 (HTRA1) cause cerebral vasculopathy. Here, authors establish mechanistically distinct protein repair approaches to reverse the deleterious effects of pathogenic mutations interfering with the assembly and protease function of HTRA1.

Here the authors show that, upon embryo implantation, signaling triggers a large-scale rearrangement of protein–RNA interactions. Phosphorylated LIN28A reassembles onto the 3′ untranslated region termini of pluripotency-associated mRNAs, where it converges with the binding of poly(A)-binding protein and drives selective mRNA decay.

Reliable measuring the voltage dynamics of individual neurons in the intact brain is significantly challenging. Here authors developed an all-optical method combining two-photon voltage imaging and optogenetics to measure and induce synaptic plasticity in vivo, revealing LTP of inhibition in cerebellar circuits and providing a blueprint to link synaptic changes to learning.

Apolipoprotein L1 genetic variants contribute to a subtype of proteinuric kidney disease referred to as APOL1-mediated kidney disease (AMKD). Here the authors report the discovery and characterization of potent and selective APOL1 ion channel inhibitors for the potential treatment of AMKD.

The ER chaperone BiP is critical for the unfolded protein response and tightly regulated through reversible AMPylation by FICD, but the structural basis is unknown. Here the authors use thiol-reactive nucleotide derivatives to stabilize the transient FICD:BiP complex and determine its crystal structure.

Targeting of diseased cells is key to the development of next-generation pharmaceuticals, but is often hindered by a lack of specific cell surface markers. Here the authors develop an RNA-based approach, which allows precise control of gene expression, with translation only occurring within preselected cell types of interest.

The glutamine fructose-6-phosphate amidotransferase 1 (GFAT-1) is the rate-limiting enzyme in the hexosamine pathway producing uridine 5’-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), an essential glycosylation precursor. Here, the authors dissect the mechanisms of GFAT-1 regulation by protein kinase A (PKA)-mediated phosphorylation.

Gut Bacteroides deploy several polysaccharide utilization loci (PULs) to forage diverse dietary and host-derived glycans. Here, the authors identify the RNA-binding protein RbpB and a family of noncoding RNAs as key players in post-transcriptional PUL regulation, further showing that ablation of RbpB in Bacteroides thetaiotaomicron compromises colonization in the mouse gut in a diet-dependent manner.

This study describes the second, shortened chloroplast variant of the ribosome-associated molecular chaperone termed trigger factor. While lacking chaperone activity, it rather contributes to maturation of the 50S ribosome subunit, particularly during plant cold acclimation.

Bed nucleus of the stria terminalis (BNST) neurons that synthesize and release the stress neuropeptide corticotropin-releasing factor drive binge alcohol drinking and anxiety. The authors describe a complex feedforward inhibitory PVT^VGLUT2-BNST^CRF circuit in mice that plays sex-dependent roles in alcohol drinking and avoidance behavior.

Many enzymes form homo-oligomers, but it is often not clear why. This study follows the evolution self-assembly in citrate synthases across their phylogeny and finds it to be variable and not obviously related to enzyme function.