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The de novo design of functional membrane proteins is a formidable challenge. Now, water-soluble peptides have been designed that assemble into α-helical barrels with accessible, polar and hydrated central channels. Insights from these structures have been used to produce stable membrane-spanning, cation-selective channels.

Lithium mining is both energy and land intensive. The use of a 3D porous natural cellulose fibre structure enables an interfacial crystallization method for the selective extraction of lithium from both brine and seawater that can be a significant alternative to mining.

Cryo-electron microscopy studies show that dynamic coordination of Na⁺ in the ion channel of Dispatched homologue 1 and the transmembrane Na⁺ gradient have key roles in exporting lipid-modified Hedgehog protein signal.

Metabolomics data from germ-free and specific-pathogen-free mice reveal effects of the microbiome on host chemistry, identifying conjugations of bile acids that are also enriched in patients with inflammatory bowel disease or cystic fibrosis.

Fruitflies require Sestrin to regulate mTORC1 signalling in response to dietary leucine, survive a diet low in leucine, and control leucine-sensitive physiological characteristics, which establishes Sestrin as a physiologically relevant leucine sensor.

Most current anti-coronavirus nanoparticle vaccines target epitopes within the RBD. Here, the authors developed nanoparticles displaying an array of spike fusion proteins derived from various coronaviruses and show that immunizing mice with these vaccines elicits broad and potent cross-reactive antibodies.

DNA analysis of 6 individuals from eastern and south-central Africa spanning the past approximately 18,000 years, and of 28 previously published ancient individuals, provides genetic evidence supporting hypotheses of increasing regionalization at the end of the Pleistocene.

Craft and colleagues show that follicular helper T cells progress through transcriptionally and functionally distinct stages that provide specific signals for germinal center regulation.

Insulin receptor protein is present in pancreatic β-cells, but the consequences of β-cell insulin resistance are incompletely understood. Here the authors use a combination of mouse studies and mathematical modelling to show that loss of beta-cell insulin receptor affects male and female mice differently and can contribute to hyperinsulinemia in the context of glucose stimulation.

How the mitochondrial electron transport chain (ETC) interacts with the NLRP3 inflammasome is somewhat unclear. Here the authors use individual complex inhibitors and new genetic models to show that ETC is critical in providing ATP via the phosphocreatine shuttle to activate the NLRP3 inflammasome.

The developmental requirements of IL-17-committed γδ T cells remain unclear. Cyster and colleagues show that the transcription factor Sox13 is selectively required for the development of the Vγ4⁺ subset of γδ T cells.

The transits of two Sun-like stars by small planets in an open star cluster are reported; such a stellar environment is unlike that of most planet-hosting field stars, and suggests that the occurrence of planets is unaffected by the stellar environment in open clusters.

Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

The peptide hormone ghrelin has previously been linked to the regulation of metabolism. This study in mice finds that increasing levels of ghrelin, either through subcutaneous injections or calorie restriction, has an anxiolytic and antidepressive effect. This reveals a previously unknown function for ghrelin.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

Hippocampal place cells contribute to navigation and memory formation. Here, the authors use in vivo glutamate imaging to reveal patterns of excitatory input received by place cell dendrites and find more spatially tuned and functionally organized inputs arriving in the place field.

A safety and efficacy trial of a single intratumoral dose of the oncolytic adenovirus DNX-2401 followed by intravenous anti-PD-1 pembrolizumab in patients with recurrent glioblastoma shows an encouraging clinical benefit rate and 12 months overall survival.

Endothelial cells form a vascular niche that supports haematopoietic stem cell function. Akt activation in endothelial cells upregulates angiocrine factors to promote long-term haematopoietic stem cell repopulation capacity while co-activation of Akt and MAPK shift the balance towards maintenance and differentiation of their progenitors.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

Idiopathic pulmonary arterial hypertension is a rare and fatal disease with a heterogeneous treatment response. Here the authors show that unsupervised machine learning of whole blood transcriptomes from 359 patients with idiopathic pulmonary arterial hypertension identifies 3 subgroups (endophenotypes) that improve risk stratification and provide new molecular insights.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

The authors describe how three types of cis-element (CTCF sites, active TSSs and TTSs) regulate cohesin trafficking along chromosomes. They uncover that this cohesin traffic pattern is genetically linked to gene regulation and RNA processing.

Barnes et al. report a dynamic and reciprocal crosstalk between tissue tension and glycocalyx bulkiness that promotes a mesenchymal, stem-like phenotype in GBM.

Ring ATPase translocases that operate on disordered substrates adopt lockwasher architectures and use a hand-over-hand mechanism. By challenging the dsDNA packaging motor of bacteriophage ϕ29 with hybrid and dsRNA, the authors propose that the motor cycles between planar and lock-washer structures.

A computational protein design was used to generate eight enzymes that were able to catalyse the Kemp elimination, a model reaction for proton transfer from carbon. Directed evolution was used to enhance the catalytic activity of the designed enzymes, demonstrating that the combination of computational protein design and directed evolution is a highly effective strategy to create novel enzymes.

B cells migrate to the outer or centre lymphoid follicle at different stages of antibody responses. Here it is shown that activated B cells must downregulate the orphan G protein-coupled receptor EBI2 to migrate to the centre follicles, where they mount T dependent antibody responses and establish germinal centres.

One of two papers detailing that mutations in the gene progranulin, which is found near MAPT on chromosome 17, can cause frontotemporal dementia, a severe neurodegenerative disorder that can affect memory, personality and motor function. The progranulin gene encodes a secreted growth factor.

Sequencing of the bonobo genome shows that more than three per cent of the human genome is more closely related to either the bonobo genome or the chimpanzee genome than those genomes are to each other.

Fragmentation of large, imperfect crystals into nanocrystals by sonication, vortexing, or vigorous pipetting facilitates atomic-resolution analysis by the cryo-EM method MicroED.

The membranes of modern cells are made of phospholipids, which are formidable barriers to the uptake of polar and charged molecules, a challenge to our understanding of the origins of cellular life. Membranes made of simple amphiphiles, such as fatty acids, allow the passage of charged molecules (such as nucleotides), while retaining longer genetic polymers made from them inside such protocells. Primitive cells could thus have acquired complex nutrients from their environment in the absence of any transport machinery.

The cytokine receptor IL-2R is essential for the development of T_reg cells; therefore, it has been difficult to separate this from its role in the suppressive function of T_reg cells. Rudensky and colleagues use various genetic systems to show that capture of IL-2 by IL-2R is important for suppression of CD8⁺ T cells but not that of CD4⁺ T cells.

The diversity of antigen receptor specificities is largely generated by random recombination of its segments. Here the authors show, by genetic comparison of monozygotic twin lymphocyte subsets, that individual genetic and epigenetic biases also contribute to the shape of the B and T cell repertoires.

Optimized adeno-associated viruses delivering split cytosine base editors and adenine base editors with trans-splicing inteins can edit brain, liver, retina, heart and skeletal-muscle tissues at therapeutically relevant efficiencies.

Single-cell analysis of lung, heart, kidney and liver autopsy samples shows the molecular and cellular changes and immune response resulting from severe COVID-19 infection.

A multifaceted approach was used to shed light on the genetic factors behind the heterogeneity that is observed in vitro and in vivo in the colony morphology of Aspergillus fumigatus isolates and on the impact of such morphological variation on fungal fitness and pathogenesis.