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Recent MPXV outbreaks underscore the need for better vaccines and treatments. Here, the authors isolate and structurally characterize potent antibodies interacting with A28 that they identify as a key viral surface protein essential for viral entry and that induces strong, protective antibody response in mice.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

RNA-binding FBF proteins control germline stem cell differentiation. Here, the authors show that three long non-coding RNAs bind, condense, and thus inhibit FBFs to promote the transition of germline stem cells into meiosis.

Learning is a dynamic process involving many cortical areas. Here, using cortex-wide imaging, the authors show that in mice learning to discriminate between two textures a distinct task related signal flow is enhanced involving a specific association area whereas other association areas are suppressed.

The transcriptional regulation of oligodendrocytes has an essential role in myelin formation and maintenance. Here, the authors identify the transcription factor Tfii-i as a regulator of myelin genes expression in the nervous system and show that its loss enhances myelin thickness and nerve conduction.

The basal ganglia process sensory and motor related information, but it is not known how movement affects sensory integration. Here, the authors show using in vivo whole-cell recordings that striatal neurons respond to both sensory stimuli and spontaneous whisking and that sensory responses are attenuated by whisking.

Studying neural circuits requires a multipronged approach. Here, the authors present a transsynaptic tracing tool in fruit fly larvae and combine it with neuronal inhibition and activation to study the circuit underlying light avoidance behaviour.

Strong coupling at the limit of a single quantum emitter has not been reported. Here, Santhosh et al.show a transparency dip is observed in the scattering spectra of individual silver bowties with one to a few quantum dots, placing the plasmonic bowtie-quantum dot constructs close to the strong coupling regime.

Dark plasmonic modes fare better in some applications due to longer lifetimes but, being subradiant, are difficult to probe. The authors apply electron energy loss spectroscopy to demonstrate that a dark mode of a plasmonic cavity can couple with a few quantum emitters to exhibit vacuum Rabi splitting.

Large protein machines are tightly regulated through allosteric communication channels. Here authors use single-molecule FRET and demonstrate the involvement of ultrafast conformational dynamics in the allosteric regulation of ClpB, a hexameric AAA+ machine that rescues aggregated proteins.

Antimicrobial resistance genes that have been mobilized between bacterial species represent a subset of the naturally occurring resistome. Here, the authors compare the abundance, diversity and geographical patterns of acquired resistance genes with latent resistance genes in global sewage metagenomes.

Strong coupling of quantum emitters to plasmonic cavities allows exploring rich phenomenologies of light-matter interaction. Here, the authors report experiments on single colloidal quantum dots coupled to plasmonic metal nanostructures, revealing complex interactions between bright and dark states.

Phenotypic persistence allows yeast and other microorganisms to endure stress conditions. Here a link is shown between DNA damage and the onset of persistence, resulting in increased genetic diversity in persister cells that could facilitate evolutionary adaptation.

A comprehensive cell atlas of the aged prefrontal cortex identifies two distinct cellular trajectories of ageing driven by specific glial and neuronal subpopulations, some of which are associated with clinicopathologic traits that define Alzheimer’s disease.

COVID-19, similarly to systemic autoimmune diseases, is characterised by the presence of autoantibodies. Authors show here that the abundance and network signature of autoantibodies targeting G protein-coupled receptors and RAS-related proteins are altered in COVID-19 patients, and the level of disruption marks clinical severity.

The dynamics of histone exchange are measured with genetically encoded timers.

Natural killer cells have emerged as critical immune cells in the response to fungal infection. Here the authors identify how Candida albicans evades the natural killer cell response via expression of ligands that directly modify the natural killer cell response and can be therapeutically targeted to restore the anti-Candida immunity.

HCV vaccine development has been challenged by difficulties in the biochemical preparation of E1E2 ectodomains. Here, the authors structurally characterize an engineered soluble E1E2 ectodomain complexed with broadly neutralizing antibodies, revealing it adopts a native fold amenable for vaccine design.

The folding of multidomain proteins can involve metastable intermediate states. Here, a single-molecule FRET based method is developed and used to identify six metastable states in the folding landscape of the three-domain protein adenylate kinase.

In our nose, some neuron subpopulations express a family of trace amine associated receptors (TAARs, smelling e.g., rotten fish). Fei et al. identify two conserved enhancers across placental mammals named TAAR enhancer 1 and 2 that coordinately regulate expression of the entire Taar gene repertoire.

The mechanisms underlying striatal cholinergic interneurons (ChINs) synchronization and its interaction with dopamine release are unclear. Here, the authors showed that polysynaptic inhibition between ChINs shapes their network activity and is mediated by dopaminergic input.

The structure of the ligand-free HIV-1–Env trimer allows conformational fixation of Env and generation of an antigen that binds CD4 with high affinity and is recognized by broadly neutralizing antibodies but not poorly neutralizing ones.

High levels of Fusobacterium nucleatum have been associated with poor overall survival in patients with colorectal and esophageal cancer. Here, the authors show that F. nucleatum is abundant in breast cancer samples and that the colonization by F. nucleatum accelerates tumor growth and metastasis in preclinical breast cancer models.

In human lymphoblastoid cell lines, 8,902 loci were identified at which genetic variation is significantly associated with local DNase I sensitivity; these variants are responsible for a large fraction of expression quantitative trait loci.

A DNA sequencing method with single-molecule fidelity detects mismatches and damage present in only one of the two DNA strands with patterns that are both similar and distinct compared to known mutation patterns.

During spermatogenic meiosis, chromatin changes due to transcription, homologous recombination, and chromosome synapsis must be coordinated. Here they show that A-MYC and BRDT regulate release of paused RNA PolII to induce a transcriptional burst during pachytene of prophase I.

Modern energy-storage technologies are based on porous electrodes that store charge within nanometrically-narrow pores or slits. Here the authors show an approach to probe and measure, for the first time, the charging dynamics within an individual nano-slit – the basic element of a porous electrode.

How cells shape signalling dynamics in MAPK cascades remains unclear. Here the authors combine mathematical modelling with in vivo validation to uncover a novel feedback mechanism that increases processivity and robustness of the yeast Hog1 module.

Animal husbandry and hunting has increased human exposure to pathogens. Here, the authors investigate the evolution of human host gene expression to Bacillus anthracis infection, the bacterium that causes anthrax disease. They observe recent positive selection, suggestive of human genome adaptation to anthrax disease.

Local heating and conduction will have a major role in the stability of nanoscale devices based on molecular junctions, so reliable methods are needed to measure the temperature of such junctions. Researchers have now developed a technique to monitor the effective temperature of current-carrying molecular junctions based on surface-enhanced Raman spectroscopy.

Eviction of histones from nucleosomes and their exchange with newly synthesized or alternative variants is a central epigenetic determinant. Here the authors implement a molecular sensor that reports on steady-state exchange of histones in mESC and mice revealing dependency between deposition of histone variant H3.3 and exchange of H3.1 and H2B in both open and closed chromatin.

Across 26 countries, Imhoff et al. find that conspiracy mentality is more prevalent at both ends of the political spectrum than the centre. This U-shaped pattern is accentuated for supporters of political parties not in government, particularly on the political right.

A crystal structure of the human immunodeficiency virus Env trimer, used by the virus to infect cells, is determined here; the new structure, which shows the pre-fusion form of Env, increases our understanding of the fusion mechanism and of how the conformation of Env allows the virus to evade the immune response.

Eitan et al. discovered genetic variants in the 3′UTR for the gene encoding IL-18 receptor that protect against ALS. The variant 3′UTR destabilizes the mRNA and dampens microglia NF-κB signaling and neurotoxicity, thus emphasizing the value of noncoding genetic association studies.

Scanning tunnelling microscopy provides evidence for topological superconductivity in a naturally occurring transition metal dichalcogenide material.

Monoclonal antibody 2F5 recognizes the membrane proximal external region (MPER) in GP41 and has broad neutralization activity against HIV-1 strains. NMR, EPR and HDX/MS analyses now show that 2F5 extracts MPER from the membrane using a scoop-like movement.

The Ebola virus glycoprotein is a target for cross-protective antibodies. Here, Janus et al. report the crystal structure of the antigen-binding fragment of a pan-reactive antibody bound to a conserved epitope of the glycoprotein, facilitating rational design of cross-protective vaccines and therapeutics.

Janus particles have a surface with two distinct physical or chemical properties; when one side is conducting and the other dielectric, the particles can be guided by an electric field. Here the authors polarize the metallic hemisphere of the particle which enables selective pickup and release of cargo.

A novel neutralizing antibody from a healthy HIV-1-infected donor that is specific for the membrane proximal region of gp41 is reported; the antibody has high potency and breadth, is not autoreactive and does not bind phospholipids.

Plasticity within neuronal microcircuits is believed to be the substrate of learning, and this study identifies two distinct disinhibitory mechanisms involving interactions between PV⁺ and SOM⁺ interneurons that dynamically regulate principal neuron activity in the amygdala and thereby control auditory fear learning.

Peptide hydrocarbon stapling is used to generate protease-resistant HIV-1 MPER antigens that mimic the conformation of viral epitopes and that are recognized by two different broadly neutralizing antibodies to HIV.

A major challenge in following electron transfer through dithiol/disulfide exchange is the dearth of accompanying spectroscopic effects. Here, the authors use single-molecule Förster resonance energy transfer experiments to illuminate disulfide bond rearrangements within the enzyme quiescin sulfhydryl oxidase.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.