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Antibody Mediated Prevention (AMP) trials showed that the broadly neutralizing antibody VRC01 could prevent some HIV-1 acquisitions. Here the authors use VRC01 levels and the sensitivity of each acquired HIV virus to predict viral loads in the AMP studies and show that VRC01 influenced viral loads, though potency was lower in vivo than expected.

Analyses of epigenomic datasets spanning transitions from normal prostate epithelium to localized prostate cancer to metastases show that latent developmental programs are reactivated in metastatic disease and that prostate lineage-specific regulatory elements are strongly enriched for prostate cancer risk heritability.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

The X-ray crystal structure of the human G-protein-coupled receptor protease-activated receptor 1 (PAR1) bound to the antagonist vorapaxar is solved, revealing an unusual method of drug binding that should facilitate the development of improved PAR1-selective antagonists.

By integrating the serum concentration of a broadly neutralizing antibody (bNAb) with its in vitro 80% inhibitory concentration, the PT₈₀ biomarker may be used to guide target levels of bNAbs for effective prevention of HIV-1 acquisition.

Tau pathology drives neuronal dysfunction in 4- repeat tauopathies. Here, the authors combine tau-PET, resting-state fMRI and histopathology data, to show that brain connectivity is associated with tau deposition patterns in 4-repeat tauopathies.

The stability of perovskite tandem solar cells is an issue. Li et al. show that diamines improve the compositional homogeneity of a low-bandgap perovskite surface and form a low-dimensional barrier that passivates defects, leading to an operational stability of over 1,000 h.

Long-term depression (LTD) of synaptic strength contributes to circuit remodeling, memory encoding and erasure. Here, the authors show that P2XR- and NMDAR-dependent LTD are associated with distinct and precise molecular modifications that lead to specific modification of synapse function.

The role of MYC in transcriptional reprogramming in prostate cancer remains poorly characterized. Here, MYC overexpression antagonizes the canonical AR transcriptional program leading to prostate tumor initiation and progression by disrupting transcriptional pause release at AR-regulated genes.

Terpene cyclases catalyze the formation of diverse hydrocarbon scaffolds found in terpenoids. Here, the authors report the cryptic function of class I terpene cyclases as aromatic prenyltransferases and the universality of this cryptic feature is confirmed using enzymes from different sources.

The authors examined neuronal responses in V1 and V2 to synthetic texture stimuli that replicate higher-order statistical dependencies found in natural images. V2, but not V1, responded differentially to these textures, in both macaque (single neurons) and human (fMRI). Human detection of naturalistic structure in the same images was predicted by V2 responses, suggesting a role for V2 in representing natural image structure.

Gold-standard evidence for correlates of protection is provided by analysis of a randomized phase 3 trial of Ad26.COV2.S for protection against moderate to severe-critical COVID-19 disease.

Authors have previously reported on the efficacy and safety of the recombinant spike protein nanoparticle vaccine, NVX-CoV2373, in healthy adults. In this work, they assess anti-spike binding IgG, anti-RBD binding IgG and neutralising antibody titer as correlates of risk and protection against COVID-19.

Antigen-activated B cells are short lived in the absence of a second signal provided by CD4⁺ T cells or cytokines. Zikherman and colleagues report that the NR4A family of nuclear receptors (NUR77 and NOR-1) are responsible for enforcing this ‘tolerance’ to self-antigen (signal 1 only) and explain, in part, why B cells are dependent upon a second signal.

Engineered live bacteria could represent a new class of therapeutic treatment for human disease. Here, the authors use a human gut-on-a-chip microfluidics system to characterize an engineered live bacterial therapeutic, designed for the treatment of phenylketonuria, and to construct mathematical models that predict therapeutic strain function in non-human primates.

Farrar and colleagues show that thymic T_reg cells are generated through two distinct developmental programs that are both required for a comprehensive T_reg cell repertoire.

Donors spins in silicon are coherent, high-performance qubits, but scale-up has been challenging. Here the authors present the first experimental demonstration of exchange-based, entangling two qubit gates between electrons bound to ³¹P donors in Si.

Combining cycloaddition and carbon–carbon cross-coupling offers a way of simplifying the enantioselective preparation of chemical building blocks, natural products and medicines such as the antipsychotic asenapine.

The immune system is known to play an important role in regenerative processes. Here, Baht and colleagues identify Metrnl, a myokine/cytokine expressed in macrophages, as mediator of muscle regeneration. Metrnl promotes macrophage IGF-1 production that, in turn, activates satellite cells.

There is little known about the function or molecular identity of the electron-dense stereocilia coat, which is transiently present at the surface of stereocilia. In this study authors screened a database of hair-cell-enriched translated proteins to identify the expression of Polycystic Kidney and Hepatic Disease 1-Like 1 (PKHD1L1), a large, mostly extracellular protein, and show that it forms the coat at the tips of stereocilia and is required for normal hearing in mice

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

The authors report on prospective exploratory analyses of circulating tumour DNA in an urothelial carcinoma immunotherapy clinical trial.

Post-stroke walking impairment is a significant public health concern. Here, the authors perform an interventional, randomized controlled trial evaluating the efficacy and safety of InTandem™, an autonomous neurorehabilitation system utilizing auditory-motor entrainment to improve walking after stroke.

Here we describe an open collaborative effort termed the ‘Ruminant T2T Consortium’. It aims to generate complete diploid assemblies for many species of ruminants to examine chromosomal evolution in the context of natural selection and domestication.

An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

The advent of immunotherapy has revolutionised cancer therapeutics, but its application in the context of pancreatic ductal adenocarcinoma has been limited. Here authors explore the effect of innate trained responses to fungal β-glucan and assess its effect in a murine model of pancreatic ductal adenocarcinoma where they observe reduced tumour burden and enhanced survival.

Herpes simplex virus 2-infected individuals are shown to have skin-tissue-resident CD8αα⁺ T cells that persist at the portal of virus release in genital skin and mucosa, possess oligoclonal T-cell-receptor-β CDR3 sequences that are stable over time, and express gene signatures of antiviral and cytolytic function indicative of viral-specific immune surveillance.

Small RNAs targeted to gene promoters are known regulators of transcription in mammalian cells. Antigene RNAs complementary to non-coding transcripts localized to the 3′ termini of genes are now shown to regulate transcription across long genomic sequences.

The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.

Small molecule antagonists of CCR6 are potential drugs for autoimmune disorders. Here the authors present inactive structures of CCR6 bound by different allosteric antagonists from two series simultaneously, offering multiple approaches to inhibit CCR6.

The manner in which antigene RNAs (agRNAs) are complementary to the progesterone receptor promoter is further examined, and the presence of an antisense transcript overlapping the promoter detected. Presence of the transcript correlates with the ability of agRNAs to activate expression and physically interact with it. Argonaute, hnRNP-k and HP1 association with the promoter DNA or antisense RNA are detected to alter upon agRNA application.

The bicyclic azetidines, a class of potent, well-tolerated antimalarial compounds that is active against multiple stages of the Plasmodium life-cycle, has been discovered following screens against libraries of compounds reminiscent of natural products.

A substudy of the CodeBreaK 101 trial, this phase 1b trial testing the KRAS-G12C inhibitor sotorasib with an anti-EGFR antibody shows an acceptable safety profile of this combination and encouraging preliminary clinical efficacy in patients with chemotherapy-refractory colorectal cancer.

In the standard Si transistor gate stack, replacing conventional dielectric HfO₂ with an ultrathin ferroelectric–antiferroelectric HfO₂–ZrO₂ heterostructure exhibiting the negative capacitance effect demonstrates ultrahigh capacitance without degradation in leakage and mobility, promising for ferroelectric integration into advanced logic technology.

Transient receptor potential (TRP) channels contribute to mechanosensation in several systems, yet direct channel gating by mechanical stimuli has been difficult to prove. Christensen and Corey consider the criteria that aim to establish direct channel gating and apply these to potential mechanosensory TRP channels.

The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types.

Auditory sensory hair cells detect sounds by deflection of their actin-based stereocilia, which vary in length. By inducing expression of GFP-actin in mouse hair cells in vivo, Narayanan et al. demonstrate that stereocilia length is regulated by very slow actin turnover, which is restricted to the tips.

Using a membrane-tethered, genetically encoded Ca²⁺ indicator, the authors describe a novel Ca²⁺ signal in hippocampal astrocytes. These 'spotty' Ca²⁺ signals were found to be mediated by astrocytic TRPA1 channels. Decreasing astrocyte resting Ca²⁺, regulated by TRPA1 channels, decreased interneuron inhibitory synapse efficacy by reducing GABA transport through GAT-3.

Fernando Pardo-Manuel de Villena and colleagues generate a 3 × 3 diallel cross of three inbred mouse lines and examine gene expression in multiple tissues. They identify allelic imbalance favoring the expression of the paternal allele across the genome.

Creating compact, lightweight and powerful optics that work well under visible light has been challenging. Here, the authors 3D print optically transparent polymers inside nanoporous glass in order to densely integrate refractive and diffractive elements, forming thin, high-performance hybrid achromatic imaging micro-optics.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.