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Few resident cell surface proteins have been identified at the axon initial segment. Here, Ogawa and colleagues use proximity labeling and proteomics to identify Contactin-1 as a transmembrane axon initial segment protein that regulates brain wiring.

Fat culturing remains a challenging task in the process of producing optimal cultivated meat. Here, using antibiotic-free culture conditions, the authors establish bovine adipose-derived stem cell spheroids as building blocks for the fabrication of cultured fat.

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.

Shock synthesis of diamond and even harder carbon polymorphs from graphite is of great interest for science and technology. Here, the authors present unprecedented in situmeasurements of the structural changes, showing ultrafast formation of diamond and, at higher pressures, evidence for a pure lonsdaleite structure.

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.

Analyses of tumor and bone marrow tissue from patients with glioblastoma demonstrate the presence of extracerebral niches that contained tumor-reactive and memory T cell subsets, including early stem-like phenotypes and stages, indicating antitumor CD8⁺ T cell differentiation in cranial bone marrow.

Mice evolved a new shape in the upper, but not in the lower molar. In addition to developmental changes specific to the upper molar, this occurred through shared changes with the lower molar, the development of which has drifted to support upper molar adaptation.

The tumour microenvironment determines which type of liver cancer develops, with transformed hepatocytes giving rise to intrahepatic cholangiocarcinoma or hepatocellular carcinoma depending or whether they are surrounded by cells undergoing necroptosis or apoptosis.

Noel et al. show aberrant updating of expectations in three distinct mouse models of autism spectrum disorder. Brain-wide neurophysiology data suggest this stems from excess units encoding deviations from prior mean and a lack of sensory prediction errors in frontal areas.

The production of nitric oxide (NO) is required for early stage embryo implantation into the uterus. Here the authors show that during differentiation of naive mouse ESCs, early production of endogenous NO leads to a mesendoderm differentiation commitment pathway by inhibiting the action of the transcriptional repressor Zeb1.

Little is known about viral-host interactions in the continental subsurface. Here, the authors use a combination of metagenomics, fluorescence in situ hybridization, and electron microscopy to show infections of abundant C-fixing subsurface archaea by lytic viruses.

Romani et al. show that matrix stiffness, confinement and applied forces impact mitochondrial dynamics and DRP1- and MIEF1-dependent mitochondrial fission regulates transcription factors in response to mechanical cues.

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.

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.

The Tyrolean Iceman is 5,300 years old and his mitochondrial genome has been previously sequenced. This study reports the full genome sequence of the Iceman and reveals that he probably had brown eyes, was at risk for coronary disease and may have been infected with the pathogen Lyme borreliosis.

Gs heterotrimers are considered to be poor providers of free Gβγ subunits. Here, the authors show that—despite this—Gs-derived Gβγ dimers are active transducers of GPCR-initiated Ca2+ signals involving phosphoinositide-based signaling routes.

The neuronal mechanisms serving contextual memories of socially rewarding stimuli are unclear. Here the authors demonstrate that neurons in the ventral hippocampus of male mice discriminate between neutral and socially rewarding contexts, a process dependent on input from the locus coeruleus.

Centromeres are defined by the histone variant CENP-A. Using single-molecule fluorescence and cryoEM, this study shows that CENP-A and the centromeric protein CENP-B collaborate to create dynamic and open chromatin, aiding centromeric factor binding.

The model archaeon Sulfolobus acidocaldarius produces several protein filaments with specialised functions, including flagellum-like archaella, Aap pili, and adhesive threads. Here, the authors describe high-resolution structures and distinct glycosylation patterns for the three filaments, and present an integrated model of the filaments in the context of the S-layer.

By individually replacing 16 yeast genes encoding ABC transporters by GFP, mating and selecting for strains with accumulated mutations the authors create a Green Monster, a strain with deletions in all 16 genes.

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.

Tethered or ingestible delivery systems that deliver liquid microjets in axial and radial directions can be used to deliver macromolecules to different parts of the gastrointestinal tract with good bioavailability.

The structure of a human exosome–ribosome supercomplex reveals the mechanisms behind the formation of active cytoplasmic exosomes and their role in co-translational RNA decay.

Citrate synthase from the cyanobacterium Synechococcus elongatus is shown to self-assemble into Sierpiński triangles, a finding that opens up the possibility that other naturally occurring molecular-scale fractals exist.

A SARS-CoV-2-human protein contactome map uncovers an inhibitor of viral replication.

Acidic pH of respiratory aerosols in acidified indoor air settings leads to unfolding of SARS-CoV-2 spike and in consequence to disrupted attachment of SARS-CoV-2 virions to target cells.

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.

The Braun lab shows that the conserved nuclear membrane protein Lem2 interacts with the MTREC complex of the nuclear-exosome pathway to promote recruitment and degradation of ncRNAs and meiotic transcripts at the nuclear periphery in Schizosaccharomyces pombe.

The authors study mechanisms underlying neuromodulatory control of transitions between brain and behavioral states. They identify a mechanism whereby modulation of Gq activity in basolateral amygdala parvalbumin interneurons mediates the transition to a fear-associated network and behavioral state.

Jung et al. show that shelter experience boosts dopamine release in the nucleus accumbens, generating a goal-location memory. Reactivating a neuronal ensemble developed from shelter experience enables memory-guided navigation to the goal during escape.

During growth, cells need to synthesize and expand their envelope, a process that requires careful regulation. Here, Dewachter et al. show that the GTPase ObgE of E. coli contributes to regulation of the synthesis of lipopolysaccharide, an essential component of the Gram-negative outer membrane.

By comparing signalling of two receptor pathways in the same cell-type, the study describes maintenance of signalling specificity at a single-cell level and the role of MAPK networks in this process.

Seismic anisotropy data for the Great Basin region of the western United States, coupled with tomographic images, help delineate a northeast-dipping lithospheric drip. Numerical experiments suggest that the drip could have formed owing to gravitational instability triggered by a density increase of about 1% and a temperature increase of about 10%.