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Kathiriya et al. identify a cardiac progenitor lineage with expression of Tbx5 and anterior heart field-specific expression of Mef2c that bisects the intraventricular septum during development and show that alterations in this lineage lead to congenital heart defects in mice.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Here, the authors develop the Gut Microbiome Wellness Index 2 (GMWI2), an enhanced version of the original GMWI prototype, designed as a disease-agnostic health status indicator based on gut microbiome taxonomic profiles.

The efficacy of CAR-T cells against solid tumors is still limited by immunosuppressive factors. Here, the authors show that engineering of CAR T cells with A1R enhances their efficacy against solid tumors in vitro and in vivo.

The role of type I interferon signalling in the control of myeloid derived suppressor cells (MDSC) activity remains controversial. Here the authors show that downregulation of type I interferon receptor is observed in MDSC from cancer patients and tumor-bearing mice and is required for the activation of their immune suppressive properties.

Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like T_PEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.

Global warming and pollution both have a detrimental effect on the environment but little is known about their combined effects. A study based on metal-doped nanoplastics shows how temperature rise impacts the fate of nanoplastics, for example, by increasing accumulation in fish guts.

GPR25 and its ligand define the core chemoaffinity axis GPR25–CXCL17 of the integrated extraintestinal mucosal immune system, regulating how immune responses disseminate to non-intestinal barrier tissues and with implications for understanding and manipulating immunity and inflammation.

Dystrophic Epidermolysis Bullosa is an uncurable monogenetic skin disease. Here, Neumayer et al. develop a cGMP-compatible CRISPR- and iPS cell-based approach that produces gene-corrected, autologous skin composite grafts for definitive treatment.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

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.

Transcriptomic and histological profiling of gut biopsies from multiple independent cohorts of patients with inflammatory bowel disease identifies distinct histopathological, molecular and cellular features associated with treatment response, providing insights for patient stratification and precision therapy.

Many SARS-CoV-2 infections may go undetected through conventional PCR or lateral flow tests. Here, the authors analyse the utility of analysing longitudinal nucleocapsid antibody trajectories to improve identification of prior SARS-CoV-2 infections using surveillance data from the UK.

Site-specific recombinases such as the Cre-LoxP system are routinely used for genome engineering in both prokaryotes and eukaryotes. Here the authors develop 63 symmetrical LoxP variants and test 1192 pairwise combinations to determine their cross-reactivity and specificity upon Cre activation.

Perception and appreciation of food flavour depends on many factors, posing a challenge for effective prediction. Here, the authors combine extensive chemical and sensory analyses of 250 commercial Belgian beers to train machine learning models that enable flavour and consumer appreciation prediction.

A biologically-interpretable and robust metric that provides insight into one’s health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, the authors introduce a species-level index that predicts the likelihood of having a disease.

Contact tracing is critical to controlling COVID-19, but most protocols only “forward-trace” to notify people who were recently exposed. Using a stochastic branching-process model, the authors show that “bidirectional” tracing to identify infector individuals and their other infectees robustly improves outbreak control.

Here the authors show that high expression of MCT11 is key to the dysfunctionality associated with exhausted CD8⁺ T cells in tumors. By targeting MCT11, uptake of lactic acid, which is abundant in the tumor, is reduced, resulting in improved effector functions and tumor immunity.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Betalains are bright red and yellow pigments, which are produced in only one order of plants, the Caryophyllales, and replace the more familiar anthocyanin pigments. The evolutionary origin of betalain production is a mystery, but a new study has identified the first regulator of betalain production and discovered a previously unknown link between the two pigment pathways.

The factors influencing risk of reinfection with SARS-CoV-2 are poorly understood. Here, the authors use data from the UK COVID-19 Infection Survey, a community based longitudinal study, to assess characteristics of ~45,000 reinfections compared to initial infections.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

CRISPRai simultaneously activates and represses two genes in single cells.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Animals form cognitive maps of the world to guide behavior. This study shows that the lateral orbitofrontal cortex is essential for creating precise, outcome-specific cognitive maps during initial learning, but not for general map creation in itself.

Missense variants in RNA-binding proteins underlie many diseases. Here the authors report an oculopharyngeal muscular dystrophy caused by heterozygous frameshift mutations in HNRNPA2B1 that alter its nucleocytoplasmic transport dynamics and result in cytoplasmic accumulation of hnRNPA2 protein.

Fine-tuning the expression of biosynthetic pathway genes is crucial to improve microbial production titres. Here, the authors present GEMbLeR, an optimization strategy to balance the expression of multiple genes simultaneously over a wide range.

Elucidation of the mechanism by which zeta inhibitory peptide erases memories, involving endocytosis of AMPA receptors on potentiated synapses, provides insight into more general mechanisms of memory maintenance and response to traumatic brain injury.

Estimates of infection rates from the UK COVID-19 Infection Survey may have been biased by the characteristics of people who chose to take part. Here, the authors show that the survey population had unusually high vaccination rates and adjust infection estimates taking this into account.

An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb targeting the CD4-binding site of Env in a HIV-1 infected individual.

Systemically administered modified siRNAs can be used in monkeys to achieve long-lasting silencing of a gene — previously, this had been established only in mice.

In vivo mutagenesis allows improving cell factories through directed evolution. Here, the authors present CoMuTER, a tool for targetable random mutagenesis of complete biosynthetic pathways using a Cas3 enzyme fused to a cytidine deaminase.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

This genome-wide association study identifies four novel risk loci for testicular germ cell tumour, and provides functional correlation between a disease-associated variant and gene expression in patient samples for one of the identified loci.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.