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Genetic studies in Drosophila combined with structural analyses show that glypicans bind palmitoylate moieties in Wnt ligands, and thus shield Wnt ligands from their aqueous environments to enable them to signal to their distant receptors.

The growing market demand for peptides is drawing more attention to their industrial synthetic procedures, which rely on large amounts of toxic solvents. Here the authors suggest practical steps that bring fully water-based peptide synthesis closer to reality.

One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

There are limited vaccines available for Ebola virus and none for broad protection from filoviruses. Here, the authors rationally design vaccines using nanoparticles and stabilized Ebola virus and other filovirus glycoproteins, characterize antibody epitopes and profile lymph node and antibody responses in mice.

Neural networks fundamentally dictate function. Here, the authors show thirteen uniquely connected neuron populations within the anterior thalamic nuclei, suggesting multiple parallel subnetworks support its emotional and cognitive functions.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

A hybrid model that combines a differentiable solver for atmospheric dynamics with machine-learning components is capable of weather forecasts and climate simulations on par with the best machine-learning and physics-based methods.

Glycosylation plays a key role in shielding of immunogenic epitopes on viral spike (S) proteins. Here Watanabe et al. report that glycans of coronavirus SARS and MERS S proteins are heterogeneously distributed and do not form an efficacious high-density global shield which would ensure efficient immune evasion.

Here the authors present an HIV-1 vaccine strategy that combines Env stabilization, nanoparticle display, and glycan trimming, which improves neutralizing antibody responses, frequency of vaccine responders, and germinal center reactions in animal models.

Typical cognitive tasks can produce robust experimental effects yet not measure individual differences reliably. Here the authors use hierarchical Bayesian analysis to develop and calibrate tasks that can efficiently achieve good reliability.

The basolateral amygdala is implicated in several behavior-related states including anxiety, autism, and addiction. The authors apply circuit-level pathway tracing methods combined with computational techniques to provide a comprehensive connectivity atlas of the mouse basolateral amygdala complex.

The dorsal peduncular area of the mouse brain functions as a network hub that integrates diverse cortical and thalamic inputs to regulate neuroendocrine and autonomic responses.

The superior colliculus (SC) receives diverse cortical inputs to drive many behaviors. Here, based on comprehensive mapping of cortico-tectal projections, the authors refined the superior colliculus into medial, centromedial, centrolateral, and lateral zones, and characterized the input-output connectivity and morphology of neurons in each zone that serve the role of SC in goal-directed behaviors.

Stabilized, native-like trimers of the HIV envelope protein, such as SOSIP trimers, are potential antigens for an HIV vaccine. Here, the authors generate a SOSIP trimer based on the consensus sequence of group M isolates, determine its structure and exposure of common epitopes, and show immunogenicity in rabbits and non-human primates.

Together with a companion paper, molecular details of immune responses in a pig-to-human xenotransplantation are identified through dense longitudinal multi-omics profiling of the xenograft and the host recipient, across the 61-day procedure.

Native-like soluble HIV envelope (Env) trimers are potential vaccine immunogens, and elimination of furin-dependence could provide a DNA-based alternative. Here, Sarkar et al. show that a cleavage-independent Env construct recapitulates the architecture and glycosylation of the native cleaved trimer.

Formamidinium lead iodide perovskite films exhibit picosecond-scale quantum transients (~2 ps), with their nanoscale superlattices defining energy levels that yield narrow emission lines and reveal the structure–emission relationship.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

In this Review, Klasse et al. explore the biogenesis and structure of the HIV-1 envelope glycoprotein (Env) and examine its functional role in viral entry. They also discuss how neutralizing antibodies interact with Env, the evolution of broadly neutralizing antibodies (bnAbs) and strategies to elicit bnAbs through germline-targeting immunogen design.

An antibody–drug conjugate that targets the pan-haematopoietic marker CD45 combined with transplanted stem cells engineered to be shielded from it can eradicate leukaemic cells while preserving haematopoiesis.

E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

A global land surface phenology map predicts complex geographical discontinuities in flowering phenology, genetic divergence and harvest seasonality across a range of taxa.

53BP1 is marker of double-strand breaks and accumulates in nuclear foci. These foci are shown to accumulate in G1 at lesions generated by replication stress and may shield lesions from erosion.

Silicification by diatoms and calcification by coccolithophores are distinct biomineralisation processes that influence global carbon cycling and the abundance of marine plankton. Here, Durak et al. show that diatom-like silicon transporters are present in coccolithophores, and that silicon is required for formation of their calcium carbonate coccoliths.

Proteomic definition of the telomeric PARylome combined with genetic and histone H3.3 deposition assays at telomeres reveals that PAR-regulated HIRA activity compensates for loss of ATRX in ALT cells.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

This study systematically mapped 2747 retrogressive thaw slumps during the past decade. It finds that higher latitude thaw slumps are mainly driven by temperature, while lower latitudes are influenced by prior-year climate and precipitation.

Volcanic fields at the eastern margin of the Red Sea rift were regarded as seismically quiet until a swarm of 30,000 earthquakes struck in 2009. Geological analyses reveal the intrusion of a volcanic dyke and indicate that rift-related extension is spread over a broad region far from the rift axis.

The crystal structure of V1/V2, the only unresolved portion of the HIV-1 gp120 envelope glycoprotein, is reported in complex with human antibody PG9 and reveals a paradigm of antibody recognition with implications for vaccine development.

Chloroquine resistance in Plasmodium falciparum is characterized using population genomics, genetic crosses and gene editing.

Ebola virus glycoprotein (GP) is a major target for vaccine design. Here, the authors identify mutations to improve GP stability and yield, design two multilayered nanoparticle carriers, and demonstrate good immunogenicity of the modified GP on nanoparticles in mice and rabbits.

Heme is an abundant cofactor required by nearly all known organisms. Here, authors discover a cyanobacterial protein with a distinct Zn-mirror heme site, which may function to sense heme and regulate energy metabolism.

A major goal of HIV-1 vaccine development is to produce antigens that can induce broadly neutralizing antibodies. Here the authors examine the underlying causes of HIV-1 envelope metastability and design uncleaved, prefusion-optimized gp140 trimers with potential for use as HIV-1 vaccine antigens.

Nasally delivered live attenuated influenza vaccines (LAIV) have been shown to be effective in vaccine trials yet immune responses are mostly measured in blood. Here the authors report a clinical trial in young adults and measure immune responses in the mucosa and blood to identify compartmentalised responses.

Batista, Schief and colleagues use a series of germline-targeting immunogens in knock-in mice expressing heavy chain sequences derived from the HIV broadly neutralizing antibody 10E8 to characterize the requirements of 10E8 B cell precursors for entry and maturation in the germinal center.

Some broadly neutralizing antibodies to HIV-1 recognize glycan-dependent epitopes on gp120. Now X-ray crystallography and EM approaches, along with functional analyses, reveal how one particular antibody (PGT135) recognizes three glycan groups and can accommodate their conformational and chemical diversity.

Chronic rhinosinusitis with nasal polyps generally has a type 2 inflammatory eosinophilic profile but can have a treatment resistant neutrophilic phenotype. Here the authors characterise nasal polyps using single cell sequencing and spatial transcriptomics and show granzyme K⁺CD8⁺ T cells associated with neutrophilic inflammation which promote release of neutrophilic chemoattractants from fibroblasts.

A practical, fully synthetic route to macrolide antibiotics via the convergent assembly of simple chemical building blocks is described; more than 300 new macrolide antibiotic candidates have been synthesized using this approach, a number of which are active against bacterial strains that are resistant to currently used antibiotics.

Many bacteria release DNA and membrane vesicles through unclear mechanisms. Here, the authors show that a prophage endolysin is involved in the explosive lysis of a sub-population of cells in Pseudomonas aeruginosa, releasing cytoplasmic content and membrane fragments that rapidly form membrane vesicles.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Programmable, RNA-guided nucleases are diverse enzymes that have been repurposed for biotechnological applications. Here, the authors mine an extensive genome-resolved metagenomics database and identified uncharacterized families of RNA-guided, compact nucleases.

The neural circuit mechanisms for sensorimotor control by the prefrontal cortex (PFC) are unclear. Here, the authors show that PFC outputs to the visual cortex and superior colliculus respectively facilitate sensory processing and action selection, allowing the PFC to independently control complementary but distinct behavioral functions.

By using a chiral halide perovskite material, spin injection at room temperature into a conventional III–V semiconductor multiple quantum well light-emitting diode is demonstrated, resulting in a semiconductor platform that can also control spin.

Here, the authors show that CD8⁺ T cells egress from tumors via lymphatic vessels in a CXCL12/CXCR4-dependent manner. High-affinity antigen encounter inhibits CXCR4 and increases retention, while no encounter or weak affinity directs T cell exit to limit local tumor control.