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Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models.

Engineering motif-specific 'hot spots' into an antibody scaffold yields antibodies with high affinity to targets containing phosphoserine, phosphothreonine or phosphotyrosine.

GABA_B receptors are the G-protein-coupled receptors for γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. Here, functional proteomics is used to show that GABA_B receptors in the brain are complexes of GABA_B1, GABA_B2 and members of a subfamily of KCTD proteins. The KCTD proteins increase the potency of agonists and markedly alter the G-protein signalling of the receptors, suggesting that they determine the pharmacology and kinetics of the receptor response.

Sweetpotato is an important food security crop providing rich source of macro- and micronutrients including carbohydrates and vitamins. Here, the authors assemble of the two diploid relatives of cultivated sweetpotato and identify genes and alleles associated with carotenoid biosynthesis from breeding lines.

Medicinal plants, often harvested directly from the wild, are under increasing pressure from climate change, development and over-exploitation in response to increasing demand. Is cultivation the answer, or can a certification programme create incentives to achieve sustainable harvests?

Here, the authors identify in the 3′ untranslated region of the genome of Usutu virus, an emerging mosquito-borne flavivirus, a sequence that confers a unique capacity to resist degradation by the ISG20 exonuclease.

Ganguli et al. show that CDKN2A loss in Barrett’s esophagus prevents esophageal adenocarcinoma initiation by counterselecting subsequent TP53 loss and report context-dependent effects of 9p21 gene co-deletions on disease progression.

Swapping the Xist/Tsix transcriptional units and placing their promoters in each other’s topologically associating domain shows that the topological partitioning of the X-inactivation center is critical to ensure proper X inactivation during development.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

Here the authors show that the preference of yeast chromatin remodeler ISW1a for dinucleosomes hinges on conformational changes that occur in the transition from binding mononucleosomes to dinucleosomes. These changes are critical for ISW1a organizing chromatin at promoters and regulating transcription in conjunction with other chromatin remodelers.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Iron homoeostasis is tightly orchestrated to avoid toxic iron overload. Here Lim and colleagues show that iron excess activates Nrf2 via mitochondrial reactive oxygen species, enhancing the expression of Bmp6 in liver sinusoidal endothelial cells, which in turn promotes hepcidin expression by hepatocytes, decreasing systemic iron levels.

The role of promoters as potential insulator elements has been largely unexplored in mammals. Here the authors show that a single nucleotide variant in the α-globin locus forms a new promoter and acts as an orientation-dependent enhancer-blocking insulator element.

Whole-genome resequencing and association analyses in 424 soybean accessions identify two homeologous genes that contributed to flowering time adaptation during soybean domestication.

Dong, Vadla et al. find that oncogenic Ras and p53 cooperatively stimulate JAK/STAT cytokines to promote non-autonomous tissue overgrowth in Drosophila. Further, blocking STAT signalling prevents the growth-inducing effect of p53 overexpression and ionising irradiation in human cancer lines in culture and in mouse xenografts, suggesting a therapeutic route.

Zhang, Chang et al. identify the protein TMEM65 as the mitochondrial Na⁺/Ca²⁺ exchanger, showing that it dimerizes to mediate ion transport and contains a binding site for a well-known inhibitor of mitochondrial Na⁺/Ca²⁺ exchange.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

In this study, the authors show that MeCP2 interacts with the NCoR/SMRT co-repressor complex and that a discrete cluster of Rett syndrome–causing mutations in the C-terminal domain of MeCP2 disrupts this interaction, impairing transcriptional repression. Knock-in mice expressing one of these MeCP2 missense mutations exhibit severe motor phenotypes.

The structural basis of how G-protein coupled receptors respond to unique stimuli remains poorly understood. Here, Krumm et al.present new structures of the neurotensin receptor and reveal insights into how ligand binding is linked to structural rearrangements associated with receptor activation.

V-domain immunoglobulin suppressor of T cell activation (VISTA) selectively engages P-selectin glycoprotein ligand-1 (PSGL-1) and suppresses T cells at acidic pH similar to those in tumour microenvironments, thereby mediating resistance to anti-tumour immune responses.

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.

The alveolar bone supports the tooth’s lifelong functionality. Here, the authors identify a tooth-specific mechanism of bone formation in which the Hedgehog–Foxf pathway regulates the alveolar bone osteoblast fates of DF progenitor cells.

RUNX1 is a large and complex gene with two alternative promoters and multiple hematopoietic enhancers. Here the authors show that unlike smaller genes Runx1 becomes sub-compartmentalized during differentiation and gene activation. This subcompartmentalization partially depends on CTCF binding at promoter-proximal CTCF sites and transcription.

Nprl3 controls erythroblast metabolism and is upregulated by α -globin enhancers sited within its introns. This arrangement couples metabolic and developmental control during erythropoiesis and may explain the ancient synteny of α -globin with Nprl3.

Analyzing and integrating a broad range of behavioral phenotypes enables prediction of underlying genetic mutations in mouse models of Huntington's disease.

Aberrant EGFR activation is commonly found in non-small cell lung cancer (NSCLC). Here the authors show that E3 ubiquitin ligase FBXL2 targets EGFR and EGFR tyrosine kinase inhibitor (TKI)-resistant mutants for proteasome-mediated degradation to inhibit EGFR-driven NSCLC growth and TKI resistance.

The Mycobacterium tuberculosis necrotizing toxin (TNT) is shown to cause toxicity by hydrolyzing NAD⁺ in the host cell. The crystal structure of TNT bound to its immunity factor reveals a new NAD⁺ glycohydrolase fold.

This Perspective argues for the use of genome engineering for restoring species genetic diversity and increase species resilience to environmental change. Genome engineering could be combined with traditional conservation approaches for more effective conservation initiatives.

Genome-wide CRISPR screens for proviral host factors of SARS-CoV-2 and HCoV-229E human coronaviruses show that the lysosomal protein TMEM106B is required for SARS-CoV-2 infection.

Metabolic rewiring supports cancer progression and therapy resistance. Here, the authors show that upregulation of the mitochondrial genome-encoded complex IV protein MT-CO2 is induced upon glucose deprivation to promote glutaminolysis through epigeneticmediated mechanisms.

A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

The small molecule GS-6207, which disrupts the function of the HIV capsid protein, shows potential as a long-acting therapeutic agent for the treatment and prevention of HIV infection.